Ординатура / Офтальмология / Английские материалы / Ocular Disease Mechanisms and Management_Levin, Albert_2010

Clinical background

Optic atrophy can be considered the wasting of a oncehealthy optic nerve. This definition excludes conditions associated with optic nerve dysplasia, hypoplasia, or aplasia in which the optic nerve is developmentally and structurally abnormal. Optic atrophy is the final common result of injury to the retinal ganglion cells, nerve fiber layer, optic nerve, chiasm, or optic tract. Additionally, prenatal or perinatal injury of posterior structures including occipital cortex may result in transsynaptic degeneration of the optic nerves.1 The range and variety of potential insults to these structures are vast and include: vascular, infectious, metabolic, traumatic, toxic, neoplastic/paraneoplastic, autoimmune/inflammatory, compressive, and inherited etiologies. The evolution of optic atrophy depends on the location and extent of injury as well as the nature of the insult (i.e., rapid progression in the case of traumatic section of the optic nerve versus slow progression in the case of optic nerve sheath meningioma). Because optic atrophy is a late marker of irreversible optic nerve injury and not a disease itself, visual symptoms are directly related to the underlying pathology.

Localizing value of optic atrophy patterns

Segmental or regional atrophy of the retinal nerve fiber layer (RNFL) or pallor of the optic disc, in concert with the clinical history and other exam findings, may have localizing value. Non­arteritic anterior ischemic optic neuropathy (NAION) often preferentially affects the superotemporal fibers, producing inferonasal visual field loss. Segmental pallor of the optic disc can often be appreciated after the acute swelling has resolved. Segmental pallor not preceded by optic disc edema may result from a nonischemic optic nerve lesion (Figure 44.1A) and may be indistinguishable from postswelling NAION.

Segmental atrophy has localizing value in the case of band atrophy (Figure 44.2) or so-called “bowtie” atrophy,2 such as in lesions of the optic chiasm or optic tract3 (Box 44.1).

Temporal pallor may be seen when a disease processes preferentially affects the maculopapillary bundle, such as toxicity, vitamin deficiency, inherited optic neuropathy, and demyelination.4 Apparent temporal pallor can be seen in

Optic atrophy

Nathan T Tagg and Randy H Kardon

normal individuals but does not represent atrophy; the nerve fiber layer coursing into the optic disc is thinnest in this region and so the neuroretinal rim may not be as pink in this sector. Additionally, there may be other factors such as an enlarged cup or a scleral temporal crescent that give the appearance of pallor when there is no atrophy.

Diffuse optic atrophy (Figure 44.1C) has less potential localizing value than segmental atrophy. If it is strictly unilateral, it localizes to the ipsilateral optic nerve. Bilateral diffuse optic atrophy has the least localizing value as it can be due to disorders of both optic nerves, optic chiasm, bilateral optic tracts or, in rare cases, bilateral postgeniculate visual structures occurring in the perinatal period (see discussion of transsynaptic degeneration, above).1

Segmental atrophy in the form of pathological cupping is seen in the case of glaucoma as notching of the neuroretinal rim (Figure 44.1D).

Mimics of optic atrophy

Any condition that causes the disc to appear pale in the absence of atrophy may lead to misdiagnosis of optic atrophy. A common condition is aphakic or pseudophakic pseudopallor (Figure 44.3E). This results after lens extraction because of loss of the light-attenuating properties of the natural lens. In a unilateral pseudophakic patient who has a nuclear cataract in the fellow eye, the difference in the color of the discs is even more pronounced because nuclear sclerosis causes the disc to appear redder than normal.5

Another condition which may mimic optic atrophy is the setting of resolved optic disc edema, in which there may be significant gliosis over the optic disc. The disc may look pale but there will be a normal or even thickened peripapillary RNFL by optical coherence tomography (OCT). Myelinated nerve fibers may also give the appearance of disc pallor (Figure 44.3A). This can be segmental (occurring in only one portion of the disc) or diffuse (covering the entire disc). Arteritic anterior ischemic optic neuropathy (AION) is occasionally associated with pallid swelling of the optic nerve during the acute stage due to optic nerve infarction (Figure 44.3B). Infiltrative diseases such as lymphoma may also present with a pale but not atrophic nerve. Buried drusen and retinitis pigmentosa (Figure 44.3C and 44.3D) are also occasionally associated with optic disc pallor, but not necessarily atrophy.

Box 44.1  Optic atrophy clinical pearls

•Band atrophy localizes to the contralateral optic tract if unilateral and the optic chiasm if bilateral

•Pallor of the temporal optic disc can be a normal finding; it should be judged in the context of all available clinical information

•Unilateral atrophy with optic disc edema in the fellow eye likely represents a subfrontal intracranial mass lesion or bilateral, nonsimultaneous nonarteritic anterior ischemic optic neuropathy

•“Pseudoatrophy” occurs when the optic disc appears pale without evidence of atrophy

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Pathophysiology

Pathogenic mechanisms of optic atrophy

Under experimental conditions, atrophy of the optic nerve occurs as a predictable, reproducible, and irreversible response to injury of retinal ganglion cells or their axons. Injured axons degenerate in both a retrograde (toward the cell body) and antegrade (wallerian degeneration – away from the cell body) fashion. An eventual additional consequence of axon injury is apoptosis of retinal ganglion cells (RGCs).

A murine model of antegrade degeneration has made use of a spontaneously occurring dominant mutation dubbed Wlds for “slow wallerian degeneration.” Mice with this mutation have significantly delayed wallerian degeneration after a variety of insults, including traumatic, toxic, and genetic insults.6 Studies indicate that important final common pathway features of antegrade degeneration include failure of antegrade axonal transport from the cell body followed by mitochondrial failure. These cause a rise in intra-axonal Ca2+ which activates calpain, a proteolytic enzyme whose activation results in degradation of the cytoskeleton and membrane proteins.7 The genetic defect in the Wlds murine model appears to resist this series of events after an experimental crush injury, delaying but not preventing atrophy. A recent study by Wang et al8 demonstrated that axon degeneration and RGC body death proceed via different cellular mechanisms. They showed that, after optic nerve axotomy, Wlds mice showed the expected delay in axonal degeneration but no delay in RGC body (retrograde) degeneration, even though the Wlds gene product appears to be located in the RGC nucleus.

While optic atrophy secondary to transsynaptic retrograde axonal degeneration (from an injury to the occipital cortex or lateral geniculate body) has been rigorously demonstrated in primates,9 evidence that it occurs in humans is anecdotal and based only on case reports.1,10 There are conflicting opinions regarding its occurrence in older children and adults11

but most authors believe this phenomenon only occurs in patients who have sustained perinatal or prenatal cerebral injuries.11,12 The cellular mechanisms which underlie transsynaptic degeneration are not well understood. In addition, there is evidence that prenatal cerebral injury results not in optic atrophy but in a specific pattern of optic nerve hypoplasia.3

Pathogenic mechanisms of optic disc pallor

The clinical hallmark of nonglaucomatous optic atrophy is pallor of the optic disc, seen ophthalmoscopically (Box 44.2). Strictly speaking, “pallor” is a subjective and comparative term that is somewhat ill-defined. To state that a disc is pale requires appreciation of “normal” disc color, which can vary widely among individuals. Furthermore, factors which may influence perception of the disc color include the color of the background fundus (a darkly colored fundus may make a normal optic disc appear relatively pale), the size of the physiologic optic cup (a larger cup shows more of the white lamina cribrosa), and the patient’s refraction (a myopic eye may have a white scleral crescent adjacent to the disc, making it appear pale).4 It is often helpful to compare the color of the disc in the fellow eye in cases of suspected unilateral optic atrophy. It is important to understand the mechanisms responsible for the development of optic disc pallor when making a diagnosis of optic atrophy.

Box 44.2  Pallor of the optic disc

•The clinical hallmark of optic atrophy is pallor of the optic disc

•Optic disc pallor occurs as a result of astrocytic element rearrangement with collapse onto the optic disc

•Nerve fiber layer loss can be measured as early as 3 weeks after optic nerve injury whereas pallor is a later manifestation

In 1977, Quigley and Anderson13 reported the results of an elegant study, entitled “The histologic basis of optic disk pallor in experimental optic atrophy.” In this study, optic nerve axotomy was performed on 10 squirrel monkeys. The clinical appearance of the fundus and histological features of the optic nerve head were followed over time. They found that several factors contributed to the appearance of optic disc pallor, including loss of RCG axons and rearrangement of astrocytes at the disc head. They did not find significantly increased astrogliosis overlying the optic disc or loss of disc capillaries. The authors postulated that the normal appearance of the neuroretinal rim was due to light traveling into the substance of the disc via the bare ganglion cell axons (a “fiberoptic” effect). The incident light diffuses among the adjacent columns of glial cells and capillaries and the reflected light is tinted by the pink color of the capillaries within the light path. However, after damage, when axons disappear secondary to atrophy, the astrocytes collapse on to the disc head (Figure 44.4) and are no longer oriented in columns but are arranged at right-angles to the entering light, reflecting it back like a mirror. Thus, pallor results from decreased transmission of light into the cytoarchitecture of the atrophic nerve head and not from absence of capillaries14 or from extensive astrocytic proliferation.13

Thus, mere loss of axonal mass at the disc head is a necessary but not sufficient condition for pallor. There must also be rearrangement and collapse of astrocytic elements onto the disc head. The time course of these changes may depend heavily on the nature and pace of the inciting injury.

Timing and evolution of optic atrophy

The development of optic atrophy in response to traumatic injury of the optic nerve has been well studied both clinically in humans and experimentally in primates and other animals. Because these studies involve sudden and complete nerve injury, they provide a framework for understanding the “worst-case scenario” of pathological and clinical changes in the optic nerve over time, i.e., the maximum rate at which changes occur.

Pathological studies of retrograde optic nerve degeneration in squirrel monkeys, involving complete axotomy of the optic nerve at the orbital apex, have shown that there is no significant change in the histologic appearance of the optic nerve proximal to the injury for up to 4 weeks after axotomy. After 6 weeks, there is definite axonal degeneration seen on histopathologic sections characterized by condensed mitochondria, crinkled lipoprotein membranes, and disintegration of microtubules. By 8 weeks, most axons proximal to the lesion were entirely disintegrated.15

Lundstrom and Frisen in 197516 described a patient who suffered complete, traumatic intracranial optic nerve transec-

Pathophysiology

C

Lamina cribrosa

Disc head

C

Lamina cribrosa

Figure 44.4  Histologic mechanism of the appearance of optic disc pallor. Top: normal: astrocytes (A) are interspersed among the axons of the optic nerve. Light is conducted into the substance of the disc by the nerve fiber bundles. Light then diffuses among the columns of astrocytes and capillaries (C) and the disc thus acquires its characteristic pink color. Bottom: atrophic state: when axons degenerate, astrocytes collapse on to the disc head at right angles to the incident light, reflecting it back. Histologically, there is no significant astrocytic gliosis that occurs, nor is there significant loss of disc capillaries. (Modified from Quigley HA, Anderson DR. The histologic basis of optic disk pallor in experimental optic atrophy. Am J Ophthalmol 1977;83:709–717.)

tion just anterior to the chiasm caused by a self-inflicted gunshot wound. The lesion resulted in no-light-perception vision with complete loss of the pupil light reflex in the ipsilateral eye and a superior temporal visual field defect in the contralateral eye . The patient was followed for 12 weeks with serial fundus photographs and ophthalmoscopy. After 25 days, there was no change in either the nerve fiber layer (assessed using red-free photography) or the appearance of the optic disc. At around 30 days, the nerve fiber layer started to show atrophy and by 47 days there was near complete loss of the nerve fiber layer. Interestingly, the optic disc still appeared normal, and without pallor at this time. Not until day 60 was there initial evidence of optic disc pallor and not until day 85 was there conspicuous pallor of the optic disc. A subset of nasal fibers from the fellow eye was also affected by the same lesion (just anterior to the chiasm) and demonstrated atrophy over the same time course. The authors concluded that retrograde atrophy occurring gradually affected the entire length of the nerve simultaneously and was not “length-dependent.” This conclusion was drawn from the observation that affected axons from both eyes atrophied at the same rate, despite the fact that affected axons from the contralateral eye were longer, coursing through the chiasm.16

Newer, more sensitive methods have been used to measure earlier changes in the nerve fiber layer after traumatic injury. In a report by Medeiros et al,17 a 14-year-old boy with traumatic optic neuropathy was studied using OCT to follow peripapillary RNFL thickness over time. As soon as 20 days after injury, the average nerve fiber layer thickness had

Figure 44.5  Time course of optic atrophy (measured) and pallor (hypothetical) after sudden intracanalicular or intracranial optic neuropathy. Shortly after the insult, there is a slight increase in the retinal nerve fiber layer (RNFL) thickness in some patients, presumably from axonal swelling at the level of the optic disc. Thereafter, the RNFL follows an exponential decline in thickness.18 Pallor is not first appreciated until about 60 days after the insult and is maximal by about 85 days.16

decreased by 40%.17 Meier et al18 documented the time course of RNFL loss by scanning laser polarimetry in 5 patients with severe acute optic neuropathy and found that it followed a model of exponential decay (Figure 44.5).

These studies suggest that measurable atrophy occurs before pallor can be detected ophthalmoscopically and only after significant atrophy does the optic nerve appear pale. They also underscore the notion that mere axonal loss is not sufficient to produce pallor; there must be rearrangement of the astroglial elements over the optic disc. This should be kept in mind by the clinician who may rely too heavily on the optic nerve appearance to detect permanent optic nerve damage.

The extent and timing of axon loss in nontraumatic lesions may not correlate well with the degree and duration of dysfunction, since many causes of injury may interfere with optic nerve conduction without permanent axonal damage. However, once permanent axon damage occurs, measurable changes in the thickness of the RNFL proceed at a rate commensurate with the nature and degree of injury. For example, atrophy secondary to an optic nerve sheath meningioma may be quite gradual over years, whereas atrophy secondary to AION will be much more rapid. In practice, many insults to the optic nerve occur over long periods of time and do not reach the threshold for triggering axonal degeneration and cell death for weeks to months or longer. It may take even more time for pallor to be appreciated.

Box 44.3  Optic nerve structure/function

relationship

•In pathological states, the relationship between optic nerve structure and function depends on the nature, pace, and extent of the injury

•In compressive and demyelinating optic neuropathies, function is often depressed far out of proportion to observed structural changes

Structure/function relationships in optic atrophy

The relationship between optic atrophy and optic nerve function is only beginning to be elucidated (Box 44.3). Hood et al19–21 demonstrated that, for certain optic neuropathies such as NAION and glaucoma, there is a strong linear correlation between RNFL thickness (measured by OCT) and visual field function (measured by standard automated perimetry). This relationship may not hold for other etiologies such as optic neuritis or compressive optic neuropathy.

On occasion, visual function is severely depressed out of proportion to the degree of RNFL axon loss. This occurs most often when conduction block is present, as in the case of chronic compressive lesions (i.e., pituitary adenoma compressing the chiasm) or demyelination (i.e., optic neuritis). It may also occur in the setting of subacute injury (i.e., not enough time has passed for atrophy or pallor to be appreciated). In the case of compression, the extent of damage is great enough to impair functioning but not (yet) great enough to induce axonal degeneration and ganglion cell apoptosis. This has important clinical implications because such patients can expect significant improvement in vision after decompression of the optic apparatus even after years of compression, providing there is preservation of the RNFL.

Conclusions

While the causes of irreversible optic nerve injury are myriad, the end result is universal: loss of RGC bodies and axons. This almost always results in pallor of the optic disc which may be diffuse or segmental, unilateral, or bilateral. When taken in context with other clinical parameters, the pattern of optic disc pallor can often help determine the localization and etiology of a problem. Absence of atrophy and pallor can be equally useful in cases of severe vision loss secondary to chronic optic nerve compression or demyelination. Recognition of common mimics of optic disc pallor is important in avoiding misdiagnosis.

2.Unsold R, Hoyt WF. Band atrophy of the optic nerve. The histology of temporal hemianopsia. Arch Ophthalmol 1980;98: 1637–1638.

6.Vargas ME, Barres BA. Why is Wallerian degeneration in the CNS so slow? Annu Rev Neurosci 2007;30:153– 179.

7.Coleman M. Axon degeneration mechanisms: commonality amid diversity. Nat Rev Neurosci 2005;6: 889–898.

8.Wang AL, Yuan M, Neufeld AH. Degeneration of neuronal cell bodies following axonal injury in Wld(S) mice. J Neurosci Res 2006;84:1799– 1807.

13.Quigley HA, Anderson DR. The histologic basis of optic disk pallor in experimental optic atrophy. Am J Ophthalmol 1977;83:709–717.

14.Radius RL, Anderson DR. The mechanism of disc pallor in experimental optic atrophy. A fluorescein angiographic study. Arch Ophthalmol 1979;97:532– 535.

15.Anderson DR. Ascending and descending optic atrophy produced

experimentally in squirrel monkeys. Am J Ophthalmol 1973;76:693–711.

16.Lundstrom M, Frisen L. Evolution of descending optic atrophy. A case report. Acta Ophthalmol (Copenh) 1975;53: 738–746.

17.Medeiros FA, Moura FC, Vessani RM, et al. Axonal loss after traumatic optic neuropathy documented by optical coherence tomography. Am J Ophthalmol 2003;135:406–408.

18.Meier FM, Bernasconi P, Sturmer J, et al. Axonal loss from acute optic neuropathy documented by scanning laser polarimetry. Br J Ophthalmol 2002;86: 285–287.

Key references

19.Hood DC, Anderson S, Rouleau J, et al. Retinal nerve fiber structure versus visual field function in patients with ischemic optic neuropathy a test of a linear model. Ophthalmology 2008;115:904–910.

20.Hood DC, Anderson SC, Wall M, et al. Structure versus function in glaucoma: an application of a linear model. Invest Ophthalmol Vis Sci 2007;48:3662– 3668.

Introduction

Nystagmus is defined as a rhythmic oscillation of the eyes. The term “nystagmus” is a transliteration of a Greek word for “drowsy head-nodding movements,” since the jerky eye movements seen in many types of nystagmus resemble the slow downward drift and upward-jerking head movements observed when sleepy. Nystagmus caused by pathology is essentially involuntary, although individuals may be able to modulate certain features of their nystagmus voluntarily. The appearance of the eye movements in nystagmus is extremely diverse.1 They can be described using a number of characteristics which can also assist in the diagnosis2,3 (Figure 45.1A):

•  Intensity: the overall speed or intensity of the eye movements can be estimated by multiplying the amplitude (degrees) with the frequency (hertz) of the eye movements.

•  Plane: nystagmus most commonly occurs along the horizontal axis, although nystagmus can also be vertical, torsional, or any combination of these, such as seesaw nystagmus (vertical with torsional) or cyclorotatory nystagmus (horizontal with vertical).

•  Waveform: historically, nystagmus has been divided into jerk nystagmus, which exhibits a quick and slow phase, and pendular nystagmus, which is a sinusoidallike oscillation without any obvious quick phase. Many nystagmus waveforms, however, are more complex, often consisting of an underlying pendular oscillation interrupted by regularly occurring quick phases.

•  Conjugacy: with most nystagmus the eyes move in tandem and are described as conjugate or associated. Disconjugate or dissociated nystagmus occurs when the eye movements differ in amplitude, frequency, waveform, or when the oscillations of the two eyes are out of phase with each other.

•  Foveation: many forms of congenital nystagmus show periods where the eyes move at a lower velocity allowing high-acuity vision at the fovea to function. The dynamics of these foveation periods can be related to visual acuity.4

•  Dependence on other parameters: certain types of nystagmus waveform are not constant but vary with

Nystagmus

Frank Proudlock and Irene Gottlob

time (e.g., can be intermittent or reverse direction), monocular or binocular viewing, convergence or eccentricity of gaze (Figure 45.1B). Nystagmus may also be associated with head movements.

Nystagmus can be grouped into infantile nystagmus, which usually appears within the first few months of life, and acquired nystagmus. Acquired nystagmus is typically associated with oscillopsia, the perception that the world is in motion.5,6 This can be extremely disabling, leading to worse visual function than is caused by low vision or age-related macular degeneration.7 Nystagmus leads to deterioration in visual acuity mainly because of deterioration in foveal vision when images move across the retina rapidly.4 The constant motion can also lead to reduced motion sensitivity.8 Nystagmus can also have a significant psychological and social impact.7

A classification scheme for pathological nystagmus has been proposed by the National Eye Institute, USA, under the Classification of Eye Movement Abnormalities and Strabismus (CEMAS).9 Nystagmus has been subdivided into: (1) infantile nystagmus syndrome; (2) fusion maldevelopment nystagmus syndrome; (3) spasmus nutans syndrome; (4) vestibular nystagmus; (5) gaze-holding deficiency nystagmus; (6) vision loss nystagmus; (7) other pendular nystagmus and nystagmus associated with disease of central myelin; (8) ocular bobbing (typical and atypical); and (9) lid nystagmus. Although the CEMAS classification is comprehensive and includes all forms of nystagmus it is mainly based on the nystagmus waveform observed using eye movement recordings which can be difficult to determine in routine clinical practice. It also pools together many forms of infantile nystagmus such as idiopathic infantile nystagmus (IIN), nystagmus associated with albinism, and achromatopsia.

The prevalence of nystagmus is 2.4 per 1000.10 The main types of childhood nystagmus are IIN, associated with albinism, nystagmus secondary to retinal disease and low vision, manifest latent nystagmus (MLN), spasmus nutans, and nystagmus due to neurological syndromes (Figure 45.2). Acquired nystagmus can result from a range of neurological disorders, of which the most common are multiple sclerosis, disease of the vestibular apparatus and innervations, insult to the nervous system caused by stroke, tumours, or trauma, and as a result of drug toxicity.

A Intensity

1 second

Frequency

Amplitude

Intensity = amplitude x frequency

Waveform

Pendular

Jerk

Complex

Foveation dynamics

BDependent upon:

Time

Infantile nystagmus

Plane

Torsional

Horizontal

Vertical

Waveform

R

Conjugate

L

R

Disconjugate

L

Foveation periods

Occlusion

Infantile nystagmus

Manifest latent nystagmus

Clinical background

MLN (classified as “fusion maldevelopment nystagmus syndrome” by CEMAS) is a predominantly horizontal, jerk nys-

tagmus that becomes more apparent when one eye is covered (Box 45.1).11 It is caused by a slow drift towards the covered eye with corrective quick phases towards the open fixing eye. In almost all patients, nystagmus is present with both eyes open: it is smaller in intensity and may be subclinical in size.12 The manifest component describes the nystagmus observed when both eyes are open and the latent component

Section 5  Neuro-ophthalmology Chapter 45  Nystagmus

Manifest latent

Idiopathic infantile

Other

Albinism

Associated with retinal disease

Neurological

Associated with low vision

Figure 45.2  A breakdown of the types of nystagmus (taken from 357 patients attending clinics in Leicester Royal Infirmary, UK, between February 2002 and October 2007).

Box 45.1  Manifest latent nystagmus

Characteristics

when one eye is covered (Figure 45.3A). MLN is associated with congenital squint syndrome which leads to disrupted binocular vision. The manifest component of MLN is due to suppression of the image from one eye. In patients who show an alternating esotropia, the direction of drift and beating can change spontaneously depending on which eye is fixing.

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Eye movements of MLN typically have “decreasing velocity” or “decelerating” slow phases and increasing intensity in abduction (Figure 45.3A). Patients with MLN can show a head turn to keep the fixating eye in adduction in order to reduce the nystagmus intensity13 (Figure 45.3B). Patients may also show a head tilt which could be part of the congenital squint syndrome unrelated to MLN or may be to compensate for the cyclovertical (i.e., torsional and vertical) component often seen in MLN.14 MLN can be treated by correcting the esotropia: this can be combined with correction of the head posture using eye muscle surgery.15 Treating the underlying amblyopia using patching therapy can also reduce the nystagmus caused by MLN.16

Pathology

The underlying mechanism behind MLN is the disruption of binocular vision during visual development. Specifically, MLN appears to result when the motion-sensitive areas of the middle temporal and medial superior temporal (MT/ MST) cortex do not develop binocular function.11

Etiology

Most commonly MLN is associated with congenital esotropia or congenital squint syndrome. A genetic component of concomitant strabismus is supported by twin studies. Inheritance does not follow mendelian patterns, however, but is more complex, with environmental risk factors contributing.17 MLN can also result from conditions that cause unilateral loss of vision during visual development such as cataract18 and optic nerve hyoplasia.19 MLN is often associated with Down syndrome.20

Pathophysiology

Insights into the cause of MLN come from neurophysio­ logical investigations in monkey models with strabismus induced using visual deprivation.11,21,22 The nucleus of the optic tract (NOT), a subcortical structure, appears to have a pivotal role in the generation of MLN (Figure 45.3C). This structure receives two types of inputs23 (indicated by right and left sides of Figure 45.3C). The NOT receives ascending projections directly from the contralateral retina and responds primarily to nasalward motion from that eye. Through this pathway a simple optokinetic response to global motion of the visual field is generated but demonstrates a monocular nasalward preference.24,25 This pathway is complementary to the rotational vestibulo-ocular reflex driven by the semicircular canals. A second projection descending from motion-sensitive MT/MST cortex causes the NOT to be driven by moving images that have no disparity between the eyes. This is a more refined level of global motion processing generating optokinetic responses to moving stimuli at a particular depth11 and requires normal binocular alignment. It drives more symmetrical horizontal optokinetic nystagmus (OKN) responses. It is complementary to the translational vestibulo-ocular reflex (horizontal), mediated by the otoliths, which has a gain dependent on viewing distance.

During early visual development, infants demonstrate a monocular nasalward preference to optokinetic stimulation due to the later development of pathways from the visual cortex causing the optokinetic response to be dominated by