Latent nystagmus and dissociated vertical–horizontal deviation

Chapter 88 Latent nystagmus and dissociated vertical–horizontal deviation


Latent nystagmus (LN) is the byproduct of fusion maldevelopment in infancy originating as an afferent visual pathway disorder. Because fusion maldevelopment – in the form of strabismus and amblyopia – is common, LN is a prevalent form of pathologic nystagmus. We have studied patients and non-human primates (NHP) with maldeveloped fusion. We have demonstrated that loss of binocular connections within area V1 (striate cortex) in the first months of life is the necessary and sufficient cause of LN. The severity of LN increases with longer durations of binocular decorrelation and greater losses of V1 connections. Decorrelation durations that exceed the equivalent of 2–3 months in human development result in a 100% LN prevalence. The binocular maldevelopment originating in area V1 is passed on to downstream, extrastriate regions of cerebral cortex that drive conjugate gaze (notably medial superior temporal-dorsal, MSTd, neurons). Conjugate gaze is stable when MSTd neurons of the right vs. left cerebral hemisphere have balanced, binocular activity. Fusion maldevelopment in infancy causes unbalanced, monocular activity. If input from one eye dominates and the other is suppressed, MSTd in one hemisphere becomes more active. Acting through downstream projections to the ipsilateral nucleus of the optic tract (NOT), the eyes are driven conjugately to that side. The unbalanced MSTd drive is evident as the nasalward gaze-holding bias of LN.

LN is the cause of dissociated vertical deviation (DVD) and dissociated horizontal deviation (DHD). Vertical vergence damping of LN evokes DVD. Relaxation of convergence damping of LN releases a latent exodeviation, or DHD. Abnormal head postures (turns and tilts) are also used to damp LN.

Latent nystagmus distinguishing characteristics and associations

Latent nystagmus (LN) is a common subtype of pathologic nystagmus observed in humans and NHPs.1 It is linked strongly to binocular maldevelopment in infancy, either from strabismus or amblyopia.

LN is characterized by a conjugate, horizontal slow-phase drift of eye position that is directed nasalward with respect to the viewing eye.2,3 When viewing switches from eye to eye, the direction of the slow-phases reverse instantaneously: leftward when the right eye is fixating and rightward when the left eye is fixating (Fig. 88.1). The severity of the nystagmus (and its visibility during clinical examination) increases when one eye is covered, hence the term “latent.” When the nystagmus is evident with both eyes open, it is called manifest LN (MLN).

LN is distinguished from congenital (“idiopathic infantile”) nystagmus (CN, or the infantile nystagmus syndrome – INS) by the feature of instantaneous reversal-of-direction with alternating fixation. By eye movement recording, it is distinguished also in waveform which is always that of decreasing velocity and linear trajectory, whereas that of CN/INS is of increasing velocity and pendular trajectory.2 Eye movement recordings, or high magnification clinical inspection with a slit-lamp or ophthalmoscope, frequently reveals a superimposed small torsional movement.

Our understanding of the clinical features of LN have been clarified by Dell’Osso et al.,2,4 who have described the historical origins of LN’s various terms. In 1872, Faucon5 first described manifest LN (MLN). In 1912, Fromaget and Fromaget6 introduced the term “nystagmus latent.” These early reports of LN were reviewed by Sorsby7 in 1931. The oxymoron “manifested latent” nystagmus was introduced by Kestenbaum8 in 1947, who emphasized that LN is often observed in patients with strabismus when they view with both eyes open.

Although infantile esotropia is the leading association with LN, any disorder that perturbs development of binocular fusion in infancy, such as monocular or severe binocular deprivation, will produce LN and MLN.9,10 The NIH Committee on Eye Movement and Strabismus (CEMAS) classification11 recommended that the terms LN/MLN be replaced by the etiologic descriptor fusion–maldevelopment nystagmus.

Development of fusion eliminates nasalward visual cortex biases

The postnatal development of binocular sensory and motor functions in normal infant monkeys parallels that of normal infant humans, but on a compressed time scale; 1 week of monkey development approximates 1 month of human.1215 Binocular disparity sensitivity and binocular fusion are absent in human and monkey neonates. Stereopsis emerges abruptly in humans during the first 3–5 months of postnatal life,1620 and in monkeys during the first 3–5 weeks,14 achieving adult-like levels of sensitivity.

V1 horizontal axonal connections are key components of fusion development and maldevelopment (Fig. 88.2). Binocularity in primates begins with horizontal connections between V1 ocular dominance columns (ODCs) of opposite ocularity.2123 These connections are immature in the first weeks of life, conveying crude, weak binocular responses.2426 Maturation of binocular connections requires correlated (synchronous) activity between right eye and left eye geniculostriate inputs.27,28 Decorrelation of inputs (Fig. 88.3), produced by binocular non-correspondence, causes loss of horizontal connections over a period of days in V1 of kittens.27,29 Similar losses occur over a period of weeks in V1 of monkeys, and over a period of months in V1 of children. Binocular decorrelation also promotes interocular suppression (Fig. 88.4) as a further hindrance to fusion.1

In the first months of life in humans and weeks of life in monkeys, monocular motion VEPs (visually evoked potentials) reveal a nasotemporal asymmetry.3033 Monocular preferential-looking testing reveals greater perceptual sensitivity to nasalward motion.34 Monocular pursuit and optokinetic tracking both reveal biases favoring nasalward target motion.12,3538 These nasalward motion biases are pronounced before onset of sensorial fusion and stereopsis, but systematically diminish thereafter. They are retained in subtle form in normal adult humans, and can be unmasked using contrived, monocular stimuli.39,40 If normal maturation of binocularity is impeded by eye misalignment or monocular deprivation, the nasalward biases persist and become pronounced.34,4147 The nasalward gaze bias is the key feature of the fusion maldevelopment syndrome. Other common findings are loss of stereopsis, interocular suppression, strabismus, and smaller amplitude torsional/vertical oscillations of the eyes.

Binocular decorrelation from various causes begins the LN cascade

Clinical studies of children43 and adults2,4,44,48 with LN have inspired a series of behavioral, physiologic, and neuroanatomic studies in NHPs who had LN associated with naturally occurring22,23,4955 or experimentally induced1,10,5665 infantile strabismus. The common finding is that the prevalence and severity of LN correlates with the age of onset and duration of binocular decorrelation in infancy.

The most common clinical cause of binocular decorrelation is strabismus, which in human infants is overwhelmingly esotropic (convergent).66 Early-onset esotropia exceeds exotropia by a ratio of 9:1. Esotropia is also the most common form of naturally occurring strabismus in NHPs.67,68 However, any prolonged deprivation of normal binocular experience in early infancy (monocular congenital cataract, uniocular high hyperopia, myopia or astigmatism, uniocular neonatal vitreous hemorrhage, uniocular corneal clouding, dense bilateral cataracts, NHP models) can cause binocular decorrelation, including monocular deprivation (uniocular amblyopia) or severe binocular deprivation (bilateral amblyopia),10,57,63 eyelid suturing (the thin, translucent eyelid of NHPs mimics a congenital cataract, allowing diffuse luminance to the retina but blocking spatial vision). Loss of spatial vision is not required; the majority of human and NHP infants with strabismus alternate fixation initially and have no amblyopia.69 The necessary and sufficient factor is binocular decorrelation, not lack of sharp visual acuity.

Decorrelation durations that exceed the equivalent of 3 months in human infant development result in an LN prevalence of 100%.1,65,70 Perturbing these inputs from week 1 of life causes LN, but delaying the perturbation to the time of onset of normal fusion and stereopsis (the equivalent of age 2–4 months in humans) is equally effective.71 The severity of the resultant LN corresponds to the severity of loss of binocular connections between ODCs of opposite ocularity in visual area V1, and the severity of interocular suppression.1,72 Area V1 feeds forward to extrastriate areas (areas MT/MST) important for gaze-holding and gaze-tracking, such as smooth pursuit, OKN, and the short-latency ocular following response.7376

Maldevelopment in V1 is passed on to areas MT/MST

Visual areas V1, V2 (prestriate cortex), MT (medial temporal), and MST (medial superior temporal) of the cerebral cortex are major components of the conjugate gaze pathway.77 Each of these areas in normal primates contains directionally selective, binocular neurons.7881 MST in each cerebral hemisphere encodes ipsiversive gaze.74,8284 MST projects downstream to the brainstem visuomotor nuclei that generate eye movements: the NOT, medial vestibular nucleus, and interconnected abducens and ocular motor nuclei.77,85 In primates, subcortical inputs to NOT may play a minor role.9,10,86 The dominant pathway is cerebral – from MST to brainstem. The dominant role of the cortical pathway, and the minimal role of a subcortical pathway, is reinforced by studies of children. Neuroimaging of visual cortex, combined with eye movement recordings, have shown absence of visually driven pursuit or OKN in cerebrally blind infants.87,88

One mechanism for the gaze-holding asymmetry would be over-representation of nasalward neurons within visual areas V1 through MT in the immature/strabismic cortex. However, directional and binocular responses of neurons in V1, V2, and MT have been investigated in infant monkeys, as well as in monkeys with early-onset strabismus, and no over-representation of neurons selective for nasalward motion has been found.26,61,89,90 In strabismic animals, binocular (excitatory) responses are reduced and interocular suppression is increased.8991 These physiologic abnormalities have neuro-anatomic correlates. In V1 of strabismic monkeys, binocular connections are deficient22,23 and interocular metabolic activity is suppressed.53,92,93

Hypothetical signal flow for LN

Figure 88.5 illustrates the mechanism for LN, showing the circuit mediating gaze-holding in primates and the role of binocular connections. Shaded structures indicate less active visual and motor neurons caused by occlusion of one eye and/or interocular suppression. The circuit on the left depicts the pathways and visuomotor component structures in a primate with LN.

Jun 4, 2016 | Posted by in OPHTHALMOLOGY | Comments Off on Latent nystagmus and dissociated vertical–horizontal deviation

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