0
We're unable to sign you in at this time. Please try again in a few minutes.
Retry
We were able to sign you in, but your subscription(s) could not be found. Please try again in a few minutes.
Retry
There may be a problem with your account. Please contact the AMA Service Center to resolve this issue.
Contact the AMA Service Center:
Telephone: 1 (800) 262-2350 or 1 (312) 670-7827  *   Email: subscriptions@jamanetwork.com
Error Message ......
Clinical Sciences |

The Optokinetic Uncover Test A New Insight Into Infantile Esotropia FREE

Michael C. Brodsky, MD; Lindsay Klaehn, COT
[+] Author Affiliations

Author Affiliations: Departments of Ophthalmology (Dr Brodsky and Ms Klaehn) and Neurology (Dr Brodsky), Mayo Clinic, Rochester, Minnesota.


JAMA Ophthalmol. 2013;131(6):759-765. doi:10.1001/jamaophthalmol.2013.2348.
Text Size: A A A
Published online

Importance We devised the optokinetic uncover test to examine the role of peripheral retinal motion input in generating horizontal optokinetic responses in patients with infantile strabismus.

Objective To ascertain whether subcortical visual input contributes to the asymmetrical monocular optokinetic responses that characterize infantile esotropia.

Design and Setting Observational study in an academic research setting.

Participants Ten patients with infantile esotropia.

Intervention Optokinetic uncover test.

Main Outcome Measures Optokinetic testing was performed in 7 patients with isolated infantile esotropia (5 untreated and 2 previously treated) and in 3 patients with infantile esotropia syndrome associated with mild neurological disease.

Results All patients showed poor temporally directed optokinetic responses that instantaneously improved when the occluded esodeviated eye was uncovered, exposing it to nasally directed optokinetic motion. This improvement in optokinetic responses did not necessitate a fixation shift to the contralateral eye.

Conclusions and Relevance Nasally directed optokinetic input to the esodeviated eye can supplement temporal monocular optokinetic responses in the fixating eye under binocular conditions. This nonfoveal optokinetic contribution suggests that monocular nasotemporal optokinetic asymmetry is partly attributable to subcortical visuovestibular responses mediated by nonfoveal retina.

Figures in this Article

Quiz Ref IDInfantile esotropia is characterized by the idiopathic onset of crossed eyes within the first 6 months of life.1 It is often accompanied by crossed fixation, primary oblique muscle overaction, latent nystagmus, and dissociated vertical divergence.2 This constellation of findings is also seen in the setting of prematurity and other neurological disorders.3

Quiz Ref IDPatients with infantile esotropia retain a monocular nasotemporal optokinetic asymmetry (MNTA) characterized by brisk monocular optokinetic responses to nasally moving optokinetic targets and poor monocular optokinetic responses to temporally moving optokinetic targets.48 The phenomenon of MNTA is believed to underlie latent nystagmus.4,710 In primates and humans, MNTA is normally seen during the first several months of life.1022 Its spontaneous resolution coincides with maturation of binocular cortical pursuit pathways that provide the temporal component for the optokinetic reflex from each eye.1021 Accordingly, the persistence of MNTA in infantile strabismus has been attributed to a cortical pursuit deficit caused by early failure of cortical binocular vision to develop.2224

Neonates show poor pursuit responses to focal moving stimuli but demonstrate strong optokinetic responses to large full-field rotating stimuli.1921 These full-field responses are attributed to the activation of subcortical optokinetic pathways that modulate full-field rotational optokinetic responses and remain active until maturation of binocular cortical pursuit pathways within the first 6 months of life.1921 This MNTA is seen in lateral-eyed afoveate animals during turning movements, in which the full-field velocity of the nasalward optokinetic stimulus to one eye determines optokinetic rotation of both eyes. Because MNTA antedates development of the visual cortex both phylogenetically and ontogenetically, debate has been waged as to whether the persistent MNTA in humans with strabismus is caused by a cortical pursuit defect, a persistent activation of subcortical optokinetic pathways, or a combination of both.3,8,10,19,25

Cortical pursuit movements in foveate animals require foveal (or perifoveal) stimulation, while subcortical optokinetic movements in afoveate animals are generated by full-field optic flow detected by peripheral retina.26 If the persistence of MNTA in humans with infantile strabismus is caused solely by defective cortical pursuit, its activation should necessitate foveal (or parafoveal) fixation. We devised the optokinetic uncover test to examine the role of peripheral retinal motion input in generating horizontal optokinetic responses in patients with infantile strabismus.

Ten patients had a history of infantile esotropia confirmed by MNTA on optokinetic testing using a handheld rotating drum (Figure 1). Patients ranged in age from 1 to 38 years, and all underwent full ophthalmological examinations with special attention to signs of crossed fixation, latent nystagmus, primary oblique muscle overaction, and amblyopia assessed by the inability to maintain fixation with one eye (Table). Seven of 10 patients had no history of neurological disease, developmental delay, or prematurity. Two of these patients had undergone previous strabismus surgery and had residual esotropia. Three of 10 patients had mild neurological disease. Two patients with mild prematurity and speech and fine-motor delays, as well as 1 patient with Down syndrome, were included because their clinical findings otherwise conformed to those of infantile esotropia.

Place holder to copy figure label and caption
Graphic Jump Location

Figure 1. Video-oculography tracing of horizontal optokinetic responses to full-field stripes (patient 4 in the ). Red line corresponds to the right eye horizontal position. Blue line corresponds to the left eye horizontal position. The first 3 beats show a poor optokinetic response when the right (amblyopic) eye is fixing a rightward (temporalward) optokinetic target. When the left eye is uncovered, the tracing improves, and fixation shifts to the left (nonamblyopic) eye. The right eye is then covered, while maintaining a rightward (nasalward) monocular stimulus to the left eye, resulting in a strong optokinetic response. The drum direction is then reversed to leftward, creating a monocular temporalward stimulus to the left eye, which produces a poor optokinetic response. When the right eye is uncovered, allowing it to receive a nasalward stimulus, the optokinetic response improves even though the left eye maintains fixation. Covering the left eye to induce a rightward (nasalward) monocular optokinetic stimulus leads to further improvement in the optokinetic waveform. OKN indicates optokinetic nystagmus.

Table Graphic Jump LocationTable. Profiles of 10 Patients Manifesting Monocular Nasotemporal Optokinetic Asymmetry

On optokinetic testing, all patients showed brisk responses to nasally directed monocular optokinetic targets and poor responses to temporally directed optokinetic targets with each eye. During attempted pursuit of temporally directed optokinetic targets, removal of the occluder from the contralateral eye produced an immediate improvement in optokinetic responses ( ). In 3 patients with alternating fixation, this improved optokinetic response produced a fixation shift to the contralateral eye, allowing the optokinetic response to be foveally driven by the eye receiving the nasally directed stimulus. In 7 patients with a fixation preference for one eye, this improved optokinetic response was accompanied by an immediate or delayed fixation shift when the preferred eye was uncovered and by maintenance of fixation when the nonpreferred eye was uncovered. In 3 patients, 3-dimensional video-oculography (Sensorimotoric Instruments) was performed using a full-field optokinetic stimulus projected on a flat surface (stripe width of 2.2° and velocity of 15° per second with the patient viewing at 3 m). These recordings confirmed that uncovering the contralateral eye produced improvement in the optokinetic waveform regardless of whether a change in fixation occurred (Figure 1). In 3 patients with mild neurological disease or prematurity, the optokinetic uncover test produced results identical to those in 7 patients with idiopathic infantile esotropia. Six of the untreated patients subsequently underwent strabismus surgery to correct their infantile esotropia. Other clinical findings are summarized in the Table.

In all patients with infantile esotropia, defective temporalward monocular optokinetic responses in the fixating eye improved when the esotropic nonfixating eye was uncovered, allowing it to receive nasalward optokinetic input under binocular conditions. From a practical viewpoint, this observation shows that the examiner should not test for MNTA when the patient has both eyes open in the patient and assume that the suppressed eye will not contribute to the optokinetic response in a patient with infantile esotropia. At a mechanistic level, this observation challenges the long-standing assumption that MNTA in humans with infantile esotropia can be attributed solely to defective cortical pursuit. In our patients, the modulation of horizontal optokinetic responses by the nonfoveal retina of the esotropic eye suggests that subcortical optokinetic pathways must continue to modulate peripheral optic flow in humans with infantile strabismus. This improvement of optokinetic waveform is consistent with the clinical observation that patients with manifest latent nystagmus show a visible worsening of their nystagmus when the deviated eye is covered.27

In a 1936 publication, Ter Braak28 showed that afoveate animals, such as the rabbit, generate optokinetic nystagmus in response to movement of large objects, despite the fact that they did not track small objects. In the monkey, these full-field optokinetic responses persisted after decortication, suggesting that they were mediated by a subcortical optokinetic system.29,30 In the rabbit, each eye is driven by mainly forward (nasalward) optokinetic motion, which provides the stimulus for the optokinetic responses of both eyes.31 These asymmetrical subcortical optokinetic responses are now known to be modulated by the contralateral nucleus of the optic tract (NOT) and dorsal terminal nucleus (DTN) of the accessory optic system within the mesencephalon, which respond only to ipsilateral optokinetic stimulation (nasalward for the viewing eye).32 In rabbits and in monkeys, these pathways project down to the inferior olive and contralateral flocculus and then on to the vestibular nuclei to modulate visuovestibular responses to full-field optokinetic rotation during turning movements (Figure 2).3335

Place holder to copy figure label and caption
Graphic Jump Location

Figure 2. Neuroanatomical pathways involved in the optokinetic reflex and optokinetic nystagmus system of the right half of the brain in the squirrel monkey. The connections of the nasal retina of the left eye and the temporal retina of the right eye are shown. Cer indicates cerebellum; d.c. IO, dorsal cap of inferior olive; EOM, extraocular muscles; GS, Scarpa ganglion of the vestibular nerve; LGN, lateral geniculate nucleus; NOT-DTN, nucleus of the optic tract–dorsal terminal nucleus; NPH, nucleus prepositus hypoglossus; NRTP, nucleus reticularis tegmenti pontis; OMN, ocular motor nuclei; PPRF, paramedian pontine reticular formation; STS, movement sensitive areas of the middle temporal area (MT) and the medial superior temporal area (MST) in the cortex around the superotemporal sulcus; V1, primary visual cortex; and VN, complex of the brainstem vestibular nuclei. Modified from the chapter by Behrens et al35 with permission.

In primates, development of binocular corticopretectal pathways to the NOT and the DTN of the accessory optic system, which provide ipsilateral pursuit responses (temporalward for the viewing eye), are necessary to cancel this optokinetic asymmetry within the first year of life (Figure 3).1118,36 These corticopretectal projections to the NOT-DTN come predominantly from the middle temporal area and the medial superior temporal area, as well as from V1 and V2,16 while those to accessory optic nuclei (lateral terminal nucleus and medial terminal nucleus) come exclusively from the middle temporal area and the medial superior temporal area.37 Within the superior temporal sulcus, the middle temporal area is involved in motion detection and is responsible for pursuit movements, while the medial superior temporal area modulates pursuit and visuovestibular detection of optic flow.38,39 As normal binocular cortical pursuit pathways become established within the first 6 months of human life, visuovestibular responses to full-field optokinetic stimulation become “encephalized” as they are incorporated into the cortical pursuit system (Figure 3).18,19

Place holder to copy figure label and caption
Graphic Jump Location

Figure 3. Normal cortical and subcortical projections during early human development (based on a model proposed by Hoffmann36). The brain is viewed from the top of the head, so the left eye is on the left. A, In early infancy, a leftward optokinetic stimulus is transmitted contralaterally via a subcortical pathway from the nasal retina of the right eye to the left nucleus of the optic tract–dorsal terminal nucleus (NOT-DTN) (solid red arrow), which is sensitive to leftward motion. Ipsilateral corticofugal input from binocular cells in the left hemisphere to the NOT-DTN (interrupted green arrow) has not yet developed. B, Later in infancy, horizontal optokinetic responses become encephalized by late infancy as binocular cortical pursuit pathways become fully operational (solid green arrow) and subcortical optokinetic pathways regress (interrupted red arrow). At this stage, a leftward optokinetic stimulus to both eyes stimulates corticofugal pathways projecting from binocular cells in V1 to the middle temporal area (MT) and the medial superior temporal area (MST) and on to the ipsilateral NOT-DTN. L indicates left eye monocular cells; LGN, lateral geniculate nucleus; R, right eye monocular cells; R + L, cortical binocular cells (that are absent in early infancy); and SCC, semicircular canals.

In humans, these same subcortical optokinetic pathways retain their nasalward directional predominance and are believed to mediate the full-field horizontal optokinetic responses that are observed in early infancy until they are rendered inactive by the establishment of binocular cortical pursuit pathways (Figure 3).20,21 However, the general notion that they can retain function in the absence of cortical input has been controversial.25,40 For example, it has been suggested that the relative preservation of responses to nasally directed stimuli in patients with incomplete bilateral occipital lobe destruction could be owing to remnants of the subcortical projection to the NOT-DTN that may have been released from cortical control.25,40,41 Ter Braak and Schenk42 described a patient with acquired cortical blindness who retained some preservation of full-field optokinetic responses, but subsequent studies43,44 have found no evidence of this effect. These findings suggest that subcortical optokinetic pathways, once “shut off” after the first few months of life, are incapable of reactivating.21,22 However, they do not address the question of whether specific derangements in binocular cortical development can act to preserve their function.

Quiz Ref IDOur finding that peripheral retinal optokinetic input can override defective foveal pursuit suggests that infantile strabismus allows these subcortical optokinetic pathways (which rely on peripheral retinal input) to remain operational. Unlike “decortication,” infantile strabismus may maintain the function of the subcortical visual pathways in a way that prevents them from being shut off. In 1983, Schor8 proposed that selective maldevelopment of cortical binocular vision could provide a competitive advantage to reinforce the activation of direct subcortical projections from the nasal retina of each eye to the contralateral NOT-DTN and thereby potentiate their function. According to Hoffmann and colleagues,11,17 the Hebbian mechanism of synaptic formation predicts that only neurons firing in a correlated manner (in this case, sharing the same direction sensitivity) become consolidated during development. Through this activity-dependent mechanism, the ipsilateral direction sensitivity of the NOT-DTN would preferentially allow crossed nasal retinogeniculate pathways that connect monocularly through the visual cortex to establish corticofugal connections to the ipsilateral NOT-DTN, enabling these latent subcortical pathways to remain functional in infantile esotropia (Figure 4).11,17 In this way, infantile esotropia could remodel the cortical motion pathways to selectively maintain the nasally biased subcortical gateway through which unbalanced binocular visual input can turn the gears on these evolutionarily ancient eye movement control systems (Figure 4).45 The fact that cortical suppression can elicit latent nystagmus,46 and that peripheral retinal input can also drive this response, suggests that selective preservation of crossed corticopretectal connections may allow these latent subcortical mechanisms to be expressed in infantile esotropia.

Place holder to copy figure label and caption
Graphic Jump Location

Figure 4. Optokinetic uncover test in infantile esotropia. A, When the right eye is covered and the left eye receives a leftward (temporal) optokinetic stimulus, the temporal retina is ineffective in generating a response. The absence of binocular cells within the visual cortex means that temporally directed stimuli cannot be transmitted to the ipsilateral nucleus of the optic tract–dorsal terminal nucleus (NOT-DTN) because maturation of this function requires an early directional match between action potentials originating from binocular cortical cells in the middle temporal area (MT) and the medial superior temporal area (MST) with those projecting from the right eye via the ipsidirectional subcortical pathway to the NOT-DTN. B, When the right eye is uncovered, the nasalward optokinetic stimulus to the right retina generates a leftward optokinetic response that could be mediated by crossed subcortical connections to the NOT-DTN (small red arrow) or through the retinogeniculate pathway to the monocular right eye cells within V1 of the left hemisphere to MT-MST, where corticofugal projections can establish connections with cells in the left NOT-DTN that share the same leftward direction preference (large red arrow). The fact that this nasalward response can be driven by peripheral retina suggests that subcortical (bottom up) optokinetic pathways rather than cortical foveal pursuit (top down) pathways have a predominant role in this response. L indicates left eye monocular cells; LGN, lateral geniculate nucleus; R, right eye monocular cells; R + L, cortical binocular cells (that are absent in infantile esotropia); and SCC, semicircular canals.

Quiz Ref IDThis explanation has several implications for the MNTA that characterizes infantile esotropia. First, a selective preservation of crossed monocular nasal retinal projections from the contralateral eye would eliminate the temporal retinal projections subserving cortical pursuit from the ipsilateral eye, explaining why the cortical component of the optokinetic asymmetry can be monocularly driven in infantile esotropia and binocularly driven with a hemispheric lesion involving the cortical pursuit pathways. Second, this neurodevelopmental derangement would help to explain how the cortical motion asymmetry in infantile esotropia is dictated the directionality of tne NOT-DTN.4749 Third, it suggests that infantile esotropia can arrest development of the nascent optokinetic system at a stage wherein MNTA can be generated from the visual cortex (top down) or from subcortical pathways (bottom up). Fourth, as divined by Schor8 30 years ago, the associated monocular corticofugal projections from the motion centers in the middle temporal area and the medial superior temporal area to the other ipsilateral accessory optic nuclei that control cyclovertical rotations of the eyes would (by a similar Hebbian mechanism) explain the torsional optokinetic biases6 and complex cyclovertical movements that accompany latent nystagmus but remain conspicuously absent in a hemispheric (binocular) pursuit defect. Fifth, the ability of subcortical visual pathways (Figure 2) to be activated bidirectionally via subcortical and cortical visual pathways would render obsolete the debate about neuroanatomical localization in infantile esotropia.3

Quiz Ref IDThis study has several inherent limitations. First, we did not use a circular full-field optokinetic apparatus, which produces the sensation of circularvection (the false sensation of physical rotation) and is believed to be necessary to directly stimulate the visuovestibular system.50 Although this testing paradigm would have fortified our conclusions, we were only able to confirm our observation using a flat full-field optokinetic stimulus, which (like the optokinetic drum) probably elicits pursuit responses in healthy individuals.50 However, the enhancement of temporalward foveal optokinetic responses when peripheral retina of the nonfixating eye was exposed to nasalward optokinetic motion demonstrates that cortical pursuit cannot be the only system involved in the generation of MNTA (and latent nystagmus, by inference). A selective preservation of crossed cortical projections to the NOT-DTN from the nasal retina of the contralateral eye (Figure 4) would allow nasalward cortical pursuit pathways to generate subcortical visuovestibular eye movements (with their associated torsional components), rendering these 2 classes of eye movement indistinguishable in the setting of infantile esotropia. Second, some of the patients with infantile esotropia had undergone previous strabismus surgery. Consequently, the angle of the esotropic deviation was smaller than that seen in infantile esotropia. Therefore, it cannot be assumed that the optokinetic uncover test would have necessarily shown a positive response in these patients with infantile esotropia prior to surgery. Nevertheless, all of our patients with unoperated infantile esotropia showed this effect, and all of our patients had an angle of deviation large enough to preclude perifoveal fixation, confirming that this binocular optokinetic mechanism arises from the synthesis of foveal and peripheral retinal input. Third, the inclusion of some patients with mild neurological disease could potentially challenge the results of our study. However, given that all patients showed the same pattern of responses on the optokinetic uncover test, our results suggest that these patients share a common pathogenesis for their infantile esotropia. Fourth, because optokinetic motion is known to displace the eyes in the direction of the fast phase,51 it might be argued that this displacement could have led to the false conclusion that the uncovered esodeviated eye was not fixating when the eye receiving temporal optokinetic stimulation was uncovered. As shown in the , however, the fixating eye was clearly evident in all patients, and video-oculography confirmed that the nasal retina of the esotropic eye could drive the optokinetic response.

In conclusion, the results of this study provide evidence that human subcortical optokinetic pathways may remain active in the presence of infantile esotropia. Selective preservation of corticotectal projections from the nasal retina of the contralateral eye would enable these subcortical visual pathways to retain their original function in the setting of infantile esotropia. The optokinetic uncover test provides a unique insight into the role of peripheral motion detection under binocular conditions, allowing us to deconstruct the optokinetic system into its cortical and subcortical components. The intrinsic monocular optokinetic biases that define these subcortical pathways may be the proximate cause of MNTA, while failure of the binocular cortical pursuit pathways to develop may provide the permissive cause that allows these subcortical pathways to remain functional.

Correspondence: Michael C. Brodsky, MD, Department of Ophthalmology, Mayo Clinic, 200 First St, Rochester, MN 55905 (Brodsky.michael@mayo.edu).

Submitted for Publication: August 30, 2012; final revision received November 21, 2012; accepted November 22, 2012.

Published Online: February 14, 2013. doi:10.1001/jamaophthalmol.2013.2348

Author Contributions: Dr Brodsky had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Conflict of Interest Disclosures: None reported.

Funding/Support: This study was supported in part by a grant from Research to Prevent Blindness.

Campos EC. Why do the eyes cross? a review and discussion of the nature and origin of essential infantile esotropia, microstrabismus, accommodative esotropia, and acute comitant esotropia.  J AAPOS. 2008;12(4):326-331
PubMed   |  Link to Article
Brodsky MC. Visuo-vestibular eye movements: infantile strabismus in 3 dimensions.  Arch Ophthalmol. 2005;123(6):837-842
PubMed   |  Link to Article
Brodsky MC. An expanded view of infantile esotropia: bottoms up!  Arch Ophthalmol. 2012;130(9):1199-1202
PubMed   |  Link to Article
Kommerell G. Ocular motor phenomena in infantile strabismus: asymmetry in optokinetic nystagmus and pursuit, latent nystagmus, and dissociated vertical divergence. In: Lennerstrand G, von Noorden GK, Campos EC, eds. Strabismus and Amblyopia: Experimental Basis for Advances in Clinical Management. New York, NY: Macmillan Press; 1988:99-109
Wright KW. Clinical optokinetic nystagmus asymmetry in treated esotropes.  J Pediatr Ophthalmol Strabismus. 1996;33(3):153-155
PubMed
Valmaggia C, Proudlock F, Gottlob I. Optokinetic nystagmus in strabismus: are asymmetries related to binocularity?  Invest Ophthalmol Vis Sci. 2003;44(12):5142-5150
PubMed   |  Link to Article
Kommerell G. Beziehungen zwischen Strabismus un Nystagmus. In: Kommerell G, ed. Augenbewegungsstörungen, Neurophysiologie und Klinik: Symposium der Deutschen Ophthalmologischen Gesellschaft, Freiburg, 1977. Munich, Germany: Bergmann; 1978:367-373
Schor CM. Subcortical binocular suppression affects the development of latent and optokinetic nystagmus.  Am J Optom Physiol Opt. 1983;60(6):481-502
PubMed   |  Link to Article
Kiorpes L, Walton PJ, O’Keefe LP, Movshon JA, Lisberger SG. Effects of early-onset artificial strabismus on pursuit eye movements and on neuronal responses in area MT of macaque monkeys.  J Neurosci. 1996;16(20):6537-6553
PubMed
Brodsky MC, Tusa RJ. Latent nystagmus: vestibular nystagmus with a twist.  Arch Ophthalmol. 2004;122(2):202-209
PubMed   |  Link to Article
Hoffmann KP. Neural basis for optokinetic defects in animals with strabismus. In: Kaufmann H, ed. Transactions of the European Strabismological Association: 16th Meeting. 1987;35-46
Dürsteler MR, Wurtz RH. Pursuit and optokinetic deficits following chemical lesions of cortical areas MT and MST.  J Neurophysiol. 1988;60(3):940-965
PubMed
Hoffmann KP, Ilg U. Role of the pretectum and accessory optic system in pursuit eye movements of the monkey. In: Berthoz A, ed. Multisensory Control of Movement. Oxford, England: Oxford University Press; 1993:93-111
Movshon JA, Lisberger SG, Kiorpes L,  et al.  Effects of artificial strabismus on pursuit eye movements and MT neurons in macaque monkeys.  Perception. 1995;24:6-7
PubMed
Distler C, Hoffmann KP. Cortical input to the nucleus of the optic tract and dorsal terminal nucleus (NOT-DTN) in macaques: a retrograde tracing study.  Cereb Cortex. 2001;11(6):572-580
PubMed   |  Link to Article
Distler C, Mustari MJ, Hoffmann KP. Cortical projections to the nucleus of the optic tract and dorsal terminal nucleus and to the dorsolateral pontine nucleus in macaques: a dual retrograde tracing study.  J Comp Neurol. 2002;444(2):144-158
PubMed   |  Link to Article
Hoffmann KP, Bremmer F, Thiele A, Distler C. Directional asymmetry of neurons in cortical areas MT and MST projecting to the NOT-DTN in macaques.  J Neurophysiol. 2002;87(4):2113-2123
PubMed
Distler C, Hoffmann KP. Visual pathway for the optokinetic reflex in infant macaque monkeys.  J Neurosci. 2011;31(48):17659-17668
PubMed   |  Link to Article
Braddick O. Where is the naso-temporal asymmetry? motion processing.  Curr Biol. 1996;6(3):250-253
PubMed   |  Link to Article
Braddick O, Atkinson J, Wattam-Bell J. Normal and anomalous development of visual motion processing: motion coherence and “dorsal-stream vulnerability.”  Neuropsychologia. 2003;41(13):1769-1784
PubMed   |  Link to Article
Braddick O, Atkinson J. Development of human visual function.  Vision Res. 2011;51(13):1588-1609
PubMed   |  Link to Article
Tychsen L. Causing and curing infantile esotropia in primates: the role of decorrelated binocular input (an American Ophthalmological Society thesis).  Trans Am Ophthalmol Soc. 2007;105:564-593
PubMed
Tychsen L, Richards M, Wong A, Foeller P, Bradley D, Burkhalter A. The neural mechanism for latent (fusion maldevelopment) nystagmus.  J Neuroophthalmol. 2010;30(3):276-283
PubMed   |  Link to Article
Tychsen L, Hurtig RR, Scott WE. Pursuit is impaired but the vestibulo-ocular reflex is normal in infantile strabismus.  Arch Ophthalmol. 1985;103(4):536-539
PubMed   |  Link to Article
Kommerell G. The relationship between infantile strabismus and latent nystagmus.  Eye (Lond). 1996;10(pt 2):274-281
PubMed   |  Link to Article
Winterson BJ, Steinman RM. The effect of luminance on human smooth pursuit of perifoveal and foveal targets.  Vision Res. 1978;18(9):1165-1172
PubMed   |  Link to Article
Dell’Osso LF, Schmidt D, Daroff RB. Latent, manifest latent, and congenital nystagmus.  Arch Ophthalmol. 1979;97(10):1877-1885
PubMed   |  Link to Article
Ter Braak JWG. Untersuchen uber optokinetischen nystagmus.  Arch Neerlandaises Physiol. 1936;21:309-376
Yee RD, Baloh RW, Honrubia V. Study of congenital nystagmus: optokinetic nystagmus.  Br J Ophthalmol. 1980;64(12):926-932
PubMed   |  Link to Article
Ter Braak JWG, Van Vliet AGM. Subcortical optokinetic nystagmus in the monkey.  Psychiatr Neurol Neurochir (Amst). 1963;66:277-283
Collewijn H, Noorduin H. Conjugate and disjunctive optokinetic eye movements in the rabbit, evoked by rotatory and translatory motion.  Pflugers Arch. 1972;335(3):173-185
PubMed   |  Link to Article
Simpson JI, Soodak RE, Hess R. The accessory optic system and its relation to the vestibulocerebellum. In: Granit R, Pampeiano O, eds. Reflex Control of Posture and Movement. Amsterdam, the Netherlands: Elsevier; 1979:715-724
Langer T, Fuchs AF, Chubb MC,  et al.  Floccular efferents in the rhesus macaque as revealed by autoradiography and horseradish peroxidase.  J Comp Neurol. 1985;235(1):26-37
Link to Article
Buttner U, Boyle R, Markert G,  et al.  Cerebellar control of eye movements. In: Freund HJ, Buttner U, Cohen B, Noth J, eds. Progress in Brain Research. Amsterdam, the Netherlands: Elsevier; 1986:225-233
Behrens F, Grusser OJ, Roggenkämper P. Open-loop and closed-loop optokinetic nystagmus in squirrel monkeys (Saimiri sciureus) and in man. In: Allum JHJ, Hulliger M, eds. Progress in Brain Research. Amsterdam, the Netherlands: Elsevier; 1989:183-196
Hoffmann KP. Cortical versus subcortical contribution to the optokinetic reflex in the cat. In: Lennerstrand G, Zee DS, Keller ELeds Basis of Ocular Motility: Proceedings of a Wenner-Gren Center and Smith-Kettlewell Eye Research Foundation I International Symposium. New York, NY: Pergamon Press; 1982:303-311
Lui F, Gregory KM, Blanks RHI, Giolli RA. Projections from visual areas of the cerebral cortex to pretectal nuclear complex, terminal accessory optic nuclei, and superior colliculus in macaque monkey.  J Comp Neurol. 1995;363(3):439-460
PubMed   |  Link to Article
Fetsch CR, Rajguru SM, Karunaratne A, Gu Y, Angelaki DE, Deangelis GC. Spatiotemporal properties of vestibular responses in area MSTd.  J Neurophysiol. 2010;104(3):1506-1522
PubMed   |  Link to Article
Chen A, DeAngelis GC, Angelaki DE. Convergence of vestibular and visual self-motion signals in an area of the posterior sylvian fissure.  J Neurosci. 2011;31(32):11617-11627
PubMed   |  Link to Article
Mehdorn E. Nasal-temporal OKN-asymmetries after bilateral occipital infarction in man. In: Lennerstrand G, Zee DS, Keller EL, eds. Functional Basis of Ocular Motility Disorders. Oxford, England: Pergamon Press; 1982:321-324
Zee DS, Tusa RJ, Herdman SJ, Butler PH, Gücer G. Effects of occipital lobectomy upon eye movements in primate.  J Neurophysiol. 1987;58(4):883-907
PubMed
Ter Braak JWG, Schenk VWD. Visual reactions in a case of long-standing cortical blindness.  J Neurol Neurosurg Psychiatry. 1971;34:140-147
Link to Article
Jung R, Kornhuber HH. Results of electronystagmography in man: the value of optokinetic, vestibular, and spontaneous nystagmus for neurologic diagnosis and research. In: Bender MB, ed. The Ocular Motor System. New York, NY: Harper & Row; 1964:428-488
Tychsen L. Absence of subcortical pathway optokinetic eye movements in an infant with cortical blindness.  Strabismus. 1996;4(1):11-14
PubMed   |  Link to Article
Brodsky MC. The accessory optic system: the fugitive visual control system in infantile strabismus.  Arch Ophthalmol. 2012;130(8):1055-1058
PubMed   |  Link to Article
Kommerell G, Zee DS. Latent nystagmus: release and suppression at will.  Invest Ophthalmol Vis Sci. 1993;34(5):1785-1792
PubMed
Norcia AM, Garcia H, Humphry R, Holmes A, Hamer RD, Orel-Bixler D. Anomalous motion VEPs in infants and in infantile esotropia.  Invest Ophthalmol Vis Sci. 1991;32(2):436-439
PubMed
Tychsen L, Lisberger SG. Maldevelopment of visual motion processing in humans who had strabismus with onset in infancy.  J Neurosci. 1986;6(9):2495-2508
PubMed
Shallo-Hoffmann J, Faldon M, Hague S, Riordan-Eva P, Fells P, Gresty M. Motion detection deficits in infantile esotropia without nystagmus.  Invest Ophthalmol Vis Sci. 1997;38(1):219-226
PubMed
Tian J, Zee DS, Walker MF. Rotational and translational optokinetic nystagmus have different kinematics.  Vision Res. 2007;47(7):1003-1010
PubMed   |  Link to Article
Garbutt S, Harwood MR, Harris CM. Anticompensatory eye position (“contraversion”) in optokinetic nystagmus.  Ann N Y Acad Sci. 2002;956:445-448
PubMed   |  Link to Article

Figures

Place holder to copy figure label and caption
Graphic Jump Location

Figure 1. Video-oculography tracing of horizontal optokinetic responses to full-field stripes (patient 4 in the ). Red line corresponds to the right eye horizontal position. Blue line corresponds to the left eye horizontal position. The first 3 beats show a poor optokinetic response when the right (amblyopic) eye is fixing a rightward (temporalward) optokinetic target. When the left eye is uncovered, the tracing improves, and fixation shifts to the left (nonamblyopic) eye. The right eye is then covered, while maintaining a rightward (nasalward) monocular stimulus to the left eye, resulting in a strong optokinetic response. The drum direction is then reversed to leftward, creating a monocular temporalward stimulus to the left eye, which produces a poor optokinetic response. When the right eye is uncovered, allowing it to receive a nasalward stimulus, the optokinetic response improves even though the left eye maintains fixation. Covering the left eye to induce a rightward (nasalward) monocular optokinetic stimulus leads to further improvement in the optokinetic waveform. OKN indicates optokinetic nystagmus.

Place holder to copy figure label and caption
Graphic Jump Location

Figure 2. Neuroanatomical pathways involved in the optokinetic reflex and optokinetic nystagmus system of the right half of the brain in the squirrel monkey. The connections of the nasal retina of the left eye and the temporal retina of the right eye are shown. Cer indicates cerebellum; d.c. IO, dorsal cap of inferior olive; EOM, extraocular muscles; GS, Scarpa ganglion of the vestibular nerve; LGN, lateral geniculate nucleus; NOT-DTN, nucleus of the optic tract–dorsal terminal nucleus; NPH, nucleus prepositus hypoglossus; NRTP, nucleus reticularis tegmenti pontis; OMN, ocular motor nuclei; PPRF, paramedian pontine reticular formation; STS, movement sensitive areas of the middle temporal area (MT) and the medial superior temporal area (MST) in the cortex around the superotemporal sulcus; V1, primary visual cortex; and VN, complex of the brainstem vestibular nuclei. Modified from the chapter by Behrens et al35 with permission.

Place holder to copy figure label and caption
Graphic Jump Location

Figure 3. Normal cortical and subcortical projections during early human development (based on a model proposed by Hoffmann36). The brain is viewed from the top of the head, so the left eye is on the left. A, In early infancy, a leftward optokinetic stimulus is transmitted contralaterally via a subcortical pathway from the nasal retina of the right eye to the left nucleus of the optic tract–dorsal terminal nucleus (NOT-DTN) (solid red arrow), which is sensitive to leftward motion. Ipsilateral corticofugal input from binocular cells in the left hemisphere to the NOT-DTN (interrupted green arrow) has not yet developed. B, Later in infancy, horizontal optokinetic responses become encephalized by late infancy as binocular cortical pursuit pathways become fully operational (solid green arrow) and subcortical optokinetic pathways regress (interrupted red arrow). At this stage, a leftward optokinetic stimulus to both eyes stimulates corticofugal pathways projecting from binocular cells in V1 to the middle temporal area (MT) and the medial superior temporal area (MST) and on to the ipsilateral NOT-DTN. L indicates left eye monocular cells; LGN, lateral geniculate nucleus; R, right eye monocular cells; R + L, cortical binocular cells (that are absent in early infancy); and SCC, semicircular canals.

Place holder to copy figure label and caption
Graphic Jump Location

Figure 4. Optokinetic uncover test in infantile esotropia. A, When the right eye is covered and the left eye receives a leftward (temporal) optokinetic stimulus, the temporal retina is ineffective in generating a response. The absence of binocular cells within the visual cortex means that temporally directed stimuli cannot be transmitted to the ipsilateral nucleus of the optic tract–dorsal terminal nucleus (NOT-DTN) because maturation of this function requires an early directional match between action potentials originating from binocular cortical cells in the middle temporal area (MT) and the medial superior temporal area (MST) with those projecting from the right eye via the ipsidirectional subcortical pathway to the NOT-DTN. B, When the right eye is uncovered, the nasalward optokinetic stimulus to the right retina generates a leftward optokinetic response that could be mediated by crossed subcortical connections to the NOT-DTN (small red arrow) or through the retinogeniculate pathway to the monocular right eye cells within V1 of the left hemisphere to MT-MST, where corticofugal projections can establish connections with cells in the left NOT-DTN that share the same leftward direction preference (large red arrow). The fact that this nasalward response can be driven by peripheral retina suggests that subcortical (bottom up) optokinetic pathways rather than cortical foveal pursuit (top down) pathways have a predominant role in this response. L indicates left eye monocular cells; LGN, lateral geniculate nucleus; R, right eye monocular cells; R + L, cortical binocular cells (that are absent in infantile esotropia); and SCC, semicircular canals.

Tables

Table Graphic Jump LocationTable. Profiles of 10 Patients Manifesting Monocular Nasotemporal Optokinetic Asymmetry

References

Campos EC. Why do the eyes cross? a review and discussion of the nature and origin of essential infantile esotropia, microstrabismus, accommodative esotropia, and acute comitant esotropia.  J AAPOS. 2008;12(4):326-331
PubMed   |  Link to Article
Brodsky MC. Visuo-vestibular eye movements: infantile strabismus in 3 dimensions.  Arch Ophthalmol. 2005;123(6):837-842
PubMed   |  Link to Article
Brodsky MC. An expanded view of infantile esotropia: bottoms up!  Arch Ophthalmol. 2012;130(9):1199-1202
PubMed   |  Link to Article
Kommerell G. Ocular motor phenomena in infantile strabismus: asymmetry in optokinetic nystagmus and pursuit, latent nystagmus, and dissociated vertical divergence. In: Lennerstrand G, von Noorden GK, Campos EC, eds. Strabismus and Amblyopia: Experimental Basis for Advances in Clinical Management. New York, NY: Macmillan Press; 1988:99-109
Wright KW. Clinical optokinetic nystagmus asymmetry in treated esotropes.  J Pediatr Ophthalmol Strabismus. 1996;33(3):153-155
PubMed
Valmaggia C, Proudlock F, Gottlob I. Optokinetic nystagmus in strabismus: are asymmetries related to binocularity?  Invest Ophthalmol Vis Sci. 2003;44(12):5142-5150
PubMed   |  Link to Article
Kommerell G. Beziehungen zwischen Strabismus un Nystagmus. In: Kommerell G, ed. Augenbewegungsstörungen, Neurophysiologie und Klinik: Symposium der Deutschen Ophthalmologischen Gesellschaft, Freiburg, 1977. Munich, Germany: Bergmann; 1978:367-373
Schor CM. Subcortical binocular suppression affects the development of latent and optokinetic nystagmus.  Am J Optom Physiol Opt. 1983;60(6):481-502
PubMed   |  Link to Article
Kiorpes L, Walton PJ, O’Keefe LP, Movshon JA, Lisberger SG. Effects of early-onset artificial strabismus on pursuit eye movements and on neuronal responses in area MT of macaque monkeys.  J Neurosci. 1996;16(20):6537-6553
PubMed
Brodsky MC, Tusa RJ. Latent nystagmus: vestibular nystagmus with a twist.  Arch Ophthalmol. 2004;122(2):202-209
PubMed   |  Link to Article
Hoffmann KP. Neural basis for optokinetic defects in animals with strabismus. In: Kaufmann H, ed. Transactions of the European Strabismological Association: 16th Meeting. 1987;35-46
Dürsteler MR, Wurtz RH. Pursuit and optokinetic deficits following chemical lesions of cortical areas MT and MST.  J Neurophysiol. 1988;60(3):940-965
PubMed
Hoffmann KP, Ilg U. Role of the pretectum and accessory optic system in pursuit eye movements of the monkey. In: Berthoz A, ed. Multisensory Control of Movement. Oxford, England: Oxford University Press; 1993:93-111
Movshon JA, Lisberger SG, Kiorpes L,  et al.  Effects of artificial strabismus on pursuit eye movements and MT neurons in macaque monkeys.  Perception. 1995;24:6-7
PubMed
Distler C, Hoffmann KP. Cortical input to the nucleus of the optic tract and dorsal terminal nucleus (NOT-DTN) in macaques: a retrograde tracing study.  Cereb Cortex. 2001;11(6):572-580
PubMed   |  Link to Article
Distler C, Mustari MJ, Hoffmann KP. Cortical projections to the nucleus of the optic tract and dorsal terminal nucleus and to the dorsolateral pontine nucleus in macaques: a dual retrograde tracing study.  J Comp Neurol. 2002;444(2):144-158
PubMed   |  Link to Article
Hoffmann KP, Bremmer F, Thiele A, Distler C. Directional asymmetry of neurons in cortical areas MT and MST projecting to the NOT-DTN in macaques.  J Neurophysiol. 2002;87(4):2113-2123
PubMed
Distler C, Hoffmann KP. Visual pathway for the optokinetic reflex in infant macaque monkeys.  J Neurosci. 2011;31(48):17659-17668
PubMed   |  Link to Article
Braddick O. Where is the naso-temporal asymmetry? motion processing.  Curr Biol. 1996;6(3):250-253
PubMed   |  Link to Article
Braddick O, Atkinson J, Wattam-Bell J. Normal and anomalous development of visual motion processing: motion coherence and “dorsal-stream vulnerability.”  Neuropsychologia. 2003;41(13):1769-1784
PubMed   |  Link to Article
Braddick O, Atkinson J. Development of human visual function.  Vision Res. 2011;51(13):1588-1609
PubMed   |  Link to Article
Tychsen L. Causing and curing infantile esotropia in primates: the role of decorrelated binocular input (an American Ophthalmological Society thesis).  Trans Am Ophthalmol Soc. 2007;105:564-593
PubMed
Tychsen L, Richards M, Wong A, Foeller P, Bradley D, Burkhalter A. The neural mechanism for latent (fusion maldevelopment) nystagmus.  J Neuroophthalmol. 2010;30(3):276-283
PubMed   |  Link to Article
Tychsen L, Hurtig RR, Scott WE. Pursuit is impaired but the vestibulo-ocular reflex is normal in infantile strabismus.  Arch Ophthalmol. 1985;103(4):536-539
PubMed   |  Link to Article
Kommerell G. The relationship between infantile strabismus and latent nystagmus.  Eye (Lond). 1996;10(pt 2):274-281
PubMed   |  Link to Article
Winterson BJ, Steinman RM. The effect of luminance on human smooth pursuit of perifoveal and foveal targets.  Vision Res. 1978;18(9):1165-1172
PubMed   |  Link to Article
Dell’Osso LF, Schmidt D, Daroff RB. Latent, manifest latent, and congenital nystagmus.  Arch Ophthalmol. 1979;97(10):1877-1885
PubMed   |  Link to Article
Ter Braak JWG. Untersuchen uber optokinetischen nystagmus.  Arch Neerlandaises Physiol. 1936;21:309-376
Yee RD, Baloh RW, Honrubia V. Study of congenital nystagmus: optokinetic nystagmus.  Br J Ophthalmol. 1980;64(12):926-932
PubMed   |  Link to Article
Ter Braak JWG, Van Vliet AGM. Subcortical optokinetic nystagmus in the monkey.  Psychiatr Neurol Neurochir (Amst). 1963;66:277-283
Collewijn H, Noorduin H. Conjugate and disjunctive optokinetic eye movements in the rabbit, evoked by rotatory and translatory motion.  Pflugers Arch. 1972;335(3):173-185
PubMed   |  Link to Article
Simpson JI, Soodak RE, Hess R. The accessory optic system and its relation to the vestibulocerebellum. In: Granit R, Pampeiano O, eds. Reflex Control of Posture and Movement. Amsterdam, the Netherlands: Elsevier; 1979:715-724
Langer T, Fuchs AF, Chubb MC,  et al.  Floccular efferents in the rhesus macaque as revealed by autoradiography and horseradish peroxidase.  J Comp Neurol. 1985;235(1):26-37
Link to Article
Buttner U, Boyle R, Markert G,  et al.  Cerebellar control of eye movements. In: Freund HJ, Buttner U, Cohen B, Noth J, eds. Progress in Brain Research. Amsterdam, the Netherlands: Elsevier; 1986:225-233
Behrens F, Grusser OJ, Roggenkämper P. Open-loop and closed-loop optokinetic nystagmus in squirrel monkeys (Saimiri sciureus) and in man. In: Allum JHJ, Hulliger M, eds. Progress in Brain Research. Amsterdam, the Netherlands: Elsevier; 1989:183-196
Hoffmann KP. Cortical versus subcortical contribution to the optokinetic reflex in the cat. In: Lennerstrand G, Zee DS, Keller ELeds Basis of Ocular Motility: Proceedings of a Wenner-Gren Center and Smith-Kettlewell Eye Research Foundation I International Symposium. New York, NY: Pergamon Press; 1982:303-311
Lui F, Gregory KM, Blanks RHI, Giolli RA. Projections from visual areas of the cerebral cortex to pretectal nuclear complex, terminal accessory optic nuclei, and superior colliculus in macaque monkey.  J Comp Neurol. 1995;363(3):439-460
PubMed   |  Link to Article
Fetsch CR, Rajguru SM, Karunaratne A, Gu Y, Angelaki DE, Deangelis GC. Spatiotemporal properties of vestibular responses in area MSTd.  J Neurophysiol. 2010;104(3):1506-1522
PubMed   |  Link to Article
Chen A, DeAngelis GC, Angelaki DE. Convergence of vestibular and visual self-motion signals in an area of the posterior sylvian fissure.  J Neurosci. 2011;31(32):11617-11627
PubMed   |  Link to Article
Mehdorn E. Nasal-temporal OKN-asymmetries after bilateral occipital infarction in man. In: Lennerstrand G, Zee DS, Keller EL, eds. Functional Basis of Ocular Motility Disorders. Oxford, England: Pergamon Press; 1982:321-324
Zee DS, Tusa RJ, Herdman SJ, Butler PH, Gücer G. Effects of occipital lobectomy upon eye movements in primate.  J Neurophysiol. 1987;58(4):883-907
PubMed
Ter Braak JWG, Schenk VWD. Visual reactions in a case of long-standing cortical blindness.  J Neurol Neurosurg Psychiatry. 1971;34:140-147
Link to Article
Jung R, Kornhuber HH. Results of electronystagmography in man: the value of optokinetic, vestibular, and spontaneous nystagmus for neurologic diagnosis and research. In: Bender MB, ed. The Ocular Motor System. New York, NY: Harper & Row; 1964:428-488
Tychsen L. Absence of subcortical pathway optokinetic eye movements in an infant with cortical blindness.  Strabismus. 1996;4(1):11-14
PubMed   |  Link to Article
Brodsky MC. The accessory optic system: the fugitive visual control system in infantile strabismus.  Arch Ophthalmol. 2012;130(8):1055-1058
PubMed   |  Link to Article
Kommerell G, Zee DS. Latent nystagmus: release and suppression at will.  Invest Ophthalmol Vis Sci. 1993;34(5):1785-1792
PubMed
Norcia AM, Garcia H, Humphry R, Holmes A, Hamer RD, Orel-Bixler D. Anomalous motion VEPs in infants and in infantile esotropia.  Invest Ophthalmol Vis Sci. 1991;32(2):436-439
PubMed
Tychsen L, Lisberger SG. Maldevelopment of visual motion processing in humans who had strabismus with onset in infancy.  J Neurosci. 1986;6(9):2495-2508
PubMed
Shallo-Hoffmann J, Faldon M, Hague S, Riordan-Eva P, Fells P, Gresty M. Motion detection deficits in infantile esotropia without nystagmus.  Invest Ophthalmol Vis Sci. 1997;38(1):219-226
PubMed
Tian J, Zee DS, Walker MF. Rotational and translational optokinetic nystagmus have different kinematics.  Vision Res. 2007;47(7):1003-1010
PubMed   |  Link to Article
Garbutt S, Harwood MR, Harris CM. Anticompensatory eye position (“contraversion”) in optokinetic nystagmus.  Ann N Y Acad Sci. 2002;956:445-448
PubMed   |  Link to Article

Correspondence

CME


You need to register in order to view this quiz.

Multimedia

Some tools below are only available to our subscribers or users with an online account.

2,516 Views
2 Citations
×

Related Content

Customize your page view by dragging & repositioning the boxes below.

Related Multimedia
Articles Related By Topic
Related Collections
PubMed Articles
Jobs
JAMAevidence.com

Users' Guides to the Medical Literature: A Manual for Evidence-Based Clinical Practice, 3rd ed
An Illustration of Bias and Random Error

Users' Guides to the Medical Literature: A Manual for Evidence-Based Clinical Practice, 3rd ed
An Illustration of Bias and Random Error