The finding of chiasmal misrouting in albinism initially led to early speculation that patients with idiopathic infantile nystagmus may too have afferent visual pathway miswiring as the neuroanatomical substrate for their nystagmus.383 However, most studies have found no electrophysiological evidence of afferent visual pathway misrouting in idiopathic infantile nystagmus.34,249 Furthermore, the absence of hemispheric VEP asymmetry in patients with aniridia and macular hypoplasia further suggests that it is the ocular hypopigmentation rather than the associated macular hypoplasia in albinism that alters the trajectory of retinogeniculate axons.349

Shatz496 has performed neuroanatomical studies in albino (Siamese) cats and found an altered visual cortical topography and abnormal interhemispheric connections via the splenium of the corpus callosum. Although albino cats demonstrated different targets for their visual callosal connections, the organization of fibers was similar to that seen in normally pigmented cats. Apkarian and Reits have demonstrated that, despite the paucity of binocularly driven cortical neurons in areas 17, 18, and 19 of the albino visual cortex, many patients with albinism retain global stereopsis.31 Humans with albinism show a regionally specific decrease in gray matter in the occipital poles on MR imaging, corresponding to the cortical representation of the central visual field.551 This reduction is presumed to be a direct result of decreased ganglion cell numbers in the central retina in albinism.

Although it has been suggested that nystagmus in albinism is the direct result of retinogeniculate and/or subcortical visual pathway misrouting, occasional patients with albinism and asymmetrical hemispheric VEPs show no nystagmus.34 Furthermore, the nystagmus waveform is identical in idiopathic infantile nystagmus (in which there is no afferent visual pathway rerouting) and albinism, suggesting that the decreased vision associated with macular hypoplasia interferes with ocular motor calibration in the same way as other congenital or early infantile sensory system deficits to produce an anomalous recalibration that is primarily responsible for infantile nystagmus in albinism.34

Apkarian35 has suggested a testing paradigm for full-field monocular stimulation in the testing of hemispheric VEPs consisting of a luminance flash stimulus in children younger than 3 years old, both luminance flash and pattern onset for children 3–6 years old, and a pattern-onset stimulus in older patients. Pattern reversal VEP waveforms are not generally used to test for hemispheric VEPs because it has been shown that pattern reversal stimulation produces small VEPs in albinos compared with pattern-onset stimulation.349,350 Confirmation of hemispheric VEPs in neonates can be obtained using special testing methods.33

In addition to retinogeniculate, cortical, and intracortical neural misrouting, albino animals have also been found to have misrouting of their subcortical visual pathways, which are intimately involved in optokinetic responses. This find-

ing has led some to attribute the ocular instability in the albino rabbit to an abnormality in the opticokinetic pursuit system.582 In the rabbit, retinal error signals reach the inferior olivary nucleus through the accessory optic tract, independent of geniculocortical projections.524 The nucleus of the optic tract plays an important role in mediating the opticokinetic response in rabbits. In the normal animal, opticokinetic mechanisms act as a negative feedback system using retinal motion as input. If the visual world (e.g., an optokinetic drum) is rotated about the animal, a smooth ocular rotation is reflexively elicited in the direction of drum rotation by the movement of the image of the visual world across the retina.582 This negative feedback system normally acts to stabilize the eye with respect to the visual surroundings. If the “sign” of the signal flowing through the optokinetic system were to be inverted, there would be a positive feedback system that would then destabilize the eyes with respect to the visual surroundings (once the eye moves, it continues to move).252,582 Such is the case in the albino rabbit, in which anomalous retinal innervation inverts the directional selectivity of those cells in the nucleus of the optic tract that have receptive fields in the temporal retina.582

The notion that misrouting of the accessory optic tract through the inferior olive is the cause of nystagmus in albino rabbits109,252,374,375 once led to the inference that it may also cause infantile nystagmus in humans.441 However, the frequent finding of infantile nystagmus in normally pigmented individuals with no misrouting (who constitute the great majority of individuals with infantile nystagmus) makes it difficult to invoke a unique mechanism for the identical nystagmus in children with albinism.159 Boylan and Harding70 have argued that infantile nystagmus in albinos is likely attributable to poor central fixation due to lack of foveal differentiation but that afferent visual pathway miswiring might be related to the high prevalence of strabismus in children with albinism.

Despite foveal hypoplasia, spectacle or contact lens correction should be encouraged in children with albinism, because improved visual acuity and ocular alignment and reduction of abnormal head positions are among the recognized benefits.24 Children with albinism may similarly appreciate improved vision from infantile nystagmus surgery and from eye muscle surgery to treat secondary torticollis.

Achiasmia

Achiasmia is a rare condition that has been reported in several unrelated families after its initial discovery in a family of Belgian sheepdogs.162,528 In isolated achiasmia, the midchiasmal bar is absent, while the intracranial optic nerves and optic tracts remain normal in size (Fig. 8.8). These cases show no evidence of additional midline central nervous

system (CNS) abnormalities, migrational anomalies, spaceoccupying lesions, or destructive processes noted on MR imaging.62 Belgian sheep dogs with isolated achiasmia have a combination of infantile nystagmus and seesaw

nystagmus.29,36,38,136,140,164,165,171,172,579,580

Absence of the human chiasm was first documented by Apkarian et al, who applied the term “Non-decussating reti- nal-fugal fibre syndrome.”36,37 In these patients, the entire optic nerve projects to the ipsilateral visual cortex so that the visual acuity remains normal,367,533,549 the visual fields remain full, and the optic discs appear normal, but affected patients have no stereoacuity.36,37 Early onset seesaw nystagmus is a frequent feature.39,165,345,367,442 Using three-dimensional eye movement recordings, Dell’Osso et al169 found that, even in the absence of achiasmia, a subclinical seesaw nystagmus can usually be detected in patients with idiopathic infantile nystagmus.

Functional MRI analysis under monocular viewing conditions has indicated extensive bilateral activation of

striate and prestriate areas, suggesting efficient transfer of information between hemispheres.549 The polarity of the VEP distribution across the occiput is the reverse of the crossed asymmetry that has been described in albinism.29,36 Partial or complicated achiasmia may also accompany more complex malformation syndromes such as septo-optic dysplasia, midfacial defects, and basal encephaloceles.367 Unlike in isolated achiasmia, however, associated optic disc malformations and bitemporal hemianopia are usually present.

Achiasmatic zebrafish display a reversed optokinetic response that correlates with failure of the retinal ganglion cells to cross the midline and form the optic chiasm.533 Huang et al298 have hypothesized that, in the achiasmatic condition, the signal from the eye always feeds into the wrong hemisphere, leading to a nasal-temporal reversed perception. They postulated that the resulting positive feedback loop is incapable of stabilizing the visual system, causing the nystagmus, and that the attempt to compensate for the retinal slip takes the