Search

Background Spontaneity is a unique feature of the nervous system. One of the fundamentally critical and recognized forms of spontaneous motor activity is witnessed in the visuomotor system. Microsaccades, the miniature spontaneous eye movements, are critical for the visual perception. We hypothesized that microsaccades follow specific temporal patterns that are modulated by the basal ganglia output. Methods We used high-resolution video-oculography to capture microsaccades in 48 subjects (31 healthy and 17 with Parkinson's disease) when subjects were asked to hold their gaze on a straight-ahead target projected on white background. We analyzed spontaneous discharge patterns of microsaccades. Results The first analysis considering coefficient of variation in intersaccadic interval distribution demonstrated that microsaccades in Parkinson's disease are more dispersed than the control group. The second analysis scrutinized microsaccades' temporal variability and revealed 3 distinct occurrence patterns: regular rhythmic, clustered, and randomly occurring following a Poisson-like process. The regular pattern was relatively more common in Parkinson's disease. Subthalamic DBS modulated this temporal pattern. The amount of change in the temporal variability depended on the DBS-induced volume of tissue activation and its overlap with the subthalamic nucleus. The third analysis determined the autocorrelations of microsaccades within 2-second time windows. We found that Parkinson's disease altered local temporal organization in microsaccade generation, and DBS had a modulatory effect. Conclusion The microsaccades occur in 3 temporal patterns. The basal ganglia are one of the modulators of the microsaccade spontaneity.

We evaluated the effects of strabismus repair on fixational eye movements (FEMs) and stereopsis recovery in patients with fusion maldevelopment nystagmus (FMN) and patients without nystagmus. Twenty-one patients with strabismus, twelve with FMN and nine without nystagmus, were tested before and after strabismus repair. Eye-movements were recorded during a gaze-holding task under monocular viewing conditions. Fast (fixational saccades and quick phases of nystagmus) and slow (inter-saccadic drifts and slow phases of nystagmus) FEMs and bivariate contour ellipse area (BCEA) were analyzed in the viewing and non-viewing eye. Strabismus repair improved the angle of strabismus in subjects with and without FMN, however patients without nystagmus were more likely to have improvement in stereoacuity. The fixational saccade amplitudes and intersaccadic drift velocities in both eyes decreased after strabismus repair in subjects without nystagmus. The slow phase velocities were higher in patients with FMN compared to inter-saccadic drifts in patients without nystagmus. There was no change in the BCEA after surgery in either group. In patients without nystagmus, the improvement of the binocular function (stereopsis), as well as decreased fixational saccade amplitude and intersaccadic drift velocity, could be due, at least partially, to central adaptive mechanisms rendered possible by surgical realignment of the eyes. The absence of improvement in patients with FMN post strabismus repair likely suggests the lack of such adaptive mechanisms in patients with early onset infantile strabismus. Assessment of fixation eye movement characteristics can be a useful tool to predict functional improvement post strabismus repair.

The variability in motor dysfunction is not uncommon in autoimmune disorders. Antibody-mediated system-wide malfunction or effects on the neural network shared by two independent pathophysiological processes can cause such heterogeneity. We tested this prediction for motor dysfunction during gaze holding in 11 patients with increased titers of glutamic acid decarboxylase (anti-GAD) antibody. High-resolution oculography measured horizontal and vertical eye positions. The analysis was performed with customized signal processing algorithms. Downbeat and gaze-evoked nystagmus commonly coexisted; one patient had a combination of upbeat and gaze-evoked nystagmus. The nystagmus was associated with saccadic intrusions in 10 patients; all had squarewaves, but five also had saccadic oscillations. The nystagmus and saccadic intrusions, both in the same axis of eye rotations, were not uncommon. Tandem appearance of the episodes of nystagmus and saccadic intrusions suggested a coupling between the two abnormalities. We speculated a unifying framework where the anti-GAD antibody inhibited (GAD mediated) conversion of glutamate to gamma-aminobutyric acid (GABA). Paucity GABA and excess of glutamate cause nystagmus (less GABA) and high-frequency saccadic oscillations (excessive glutamate).

Jordan Murray,1 Kiran Garg,2 Fatema Ghasia3 1Cleveland Clinic Cole Eye Institute, Ophthalmological Research, Cleveland, OH, USA; 2Case Western Reserve University School of Medicine, Cleveland, OH, USA; 3Cleveland Clinic Cole Eye Institute, Department of Ophthalmology, Cleveland, OH, 44195-0001, USACorrespondence: Fatema GhasiaCleveland Clinic Cole Eye Institute, Department of Ophthalmology, 2022, East 105th Street, Cleveland, OH, 44195-0001, USAEmail fatemaghasia@gmail.comPurpose: The aim of the study is to examine the association between amblyopia type and the presence of nystagmus on binocular and monocular functions of the fellow (FE) and amblyopic eye (AE).Methods: We recruited 19 controls and 44 amblyopes (anisometropes=13, strabismic=10, mixed=21). We measured visual, grating, and vernier acuities and high/low spatial frequency (SF) contrast sensitivities in each eye using a staircase method. Stereoacuity was measured with the Titmus fly test. We recorded fixation eye movements (FEM) using high-resolution video-oculography. Subjects were classified as having either no nystagmus (n=18), fusion maldevelopment nystagmus syndrome (FMNS) (n=12), or nystagmus without any structural anomalies that does not meet the criteria for FMNS or infantile nystagmus (n=14).Results: Analysis of visual function by clinical amblyopia type showed that patients with strabismus/mixed amblyopia (F (2,54)=9.5, p< 0.001) were more likely to have poor stereopsis while controlling for AE grating acuity deficit. The FE of patients with anisometropia had greater contrast sensitivity deficits at low (F (2,43)=4.4, p=0.018) and high SF (F (2,42)=10.1, p< 0.001). Analysis of visual function by FEM characteristics (low SF: (F (3,43)=4.3, p=0.010) and high SF: (F (3,42)=7.1, p=0.001) showed that the FE of patients with FMNS had worse low and high SF contrast sensitivities, whereas those without FMNS had greater contrast sensitivity deficits only at high SF compared to controls. Patients with FMNS (F (3,54) = 12.9, p< 0.001) were more likely to have poor stereopsis while controlling for AE grating acuity deficit compared to patients without FMNS. All amblyopic patients had worse high SF contrast sensitivity of the AE irrespective of type or FEM characteristics (Type = F (2,43)=8.8, p=0.001; FEM characteristics= F (3,43)=5.1, p=0.004).Conclusion: The presence of FMNS in patients with strabismic/mixed amblyopia is associated with poor/absent stereopsis. FE deficits vary across amblyopia type. Like FEM abnormalities, visual function deficits are seen in the FE of patients with and without nystagmus.Keywords: amblyopia, fellow eye, contrast sensitivity, fusion maldevelopment nystagmus, stereopsis

The virtual practice has made major advances in the way that we care for patients in the modern era. The culture of virtual practice, consulting, and telemedicine, which had started several years ago, took an accelerated leap as humankind was challenged by the novel coronavirus pandemic (COVID19). The social distancing measures and lockdowns imposed in many countries left medical care providers with limited options in evaluating ambulatory patients, pushing the rapid transition to assessments via virtual platforms. In this novel arena of medical practice, which may form new norms beyond the current pandemic crisis, we found it critical to define guidelines on the recommended practice in neurotology, including remote methods in examining the vestibular and eye movement function. The proposed remote examination methods aim to reliably diagnose acute and subacute diseases of the inner-ear, brainstem, and the cerebellum. A key aim was to triage patients into those requiring urgent emergency room assessment versus non-urgent but expedited outpatient management. Physicians who had expertise in managing patients with vestibular disorders were invited to participate in the taskforce. The focus was on two topics: (1) an adequate eye movement and vestibular examination strategy using virtual platforms and (2) a decision pathway providing guidance about which patient should seek urgent medical care and which patient should have non-urgent but expedited outpatient management. Electronic supplementary material The online version of this article (10.1007/s12311-020-01178-8) contains supplementary material, which is available to authorized users.

Reading is a vision-reliant task, requiring sequential eye movements. Binocularly discordant input results in visual sensory and oculomotor dysfunction in amblyopia, which may contribute to reading difficulties. This study aims to determine the contributions of fixation eye movement (FEM) abnormalities, clinical type and severity of amblyopia to reading performance under binocular and monocular viewing conditions.Twenty-three amblyopic patients and nine healthy controls were recruited. Eye movements elicited during fixation and reading of preselected passages were collected for each subject using infrared video-oculography. Subjects were classified as having no nystagmus (n = 9), fusion maldevelopment nystagmus (FMN, n = 5), or nystagmus without structural anomalies that does not meet criteria for FMN or infantile nystagmus (n = 9). Reading rate (words/min), the number of forward and regressive saccades (per 100 words) and fixation duration (s) were computed.Amblyopic patients with and without nystagmus exhibited greater vergence and fixation instability. In patients without nystagmus, the instability arises from increased amplitude and velocity of fast and slow FEMs respectively. Amblyopic patients with and without nystagmus exhibited lower reading speeds with increased fixation duration, regressive and progressive saccades than controls in all viewing conditions. Mixed etiology, greater amblyopic eye visual acuity and stereopsis deficits were associated with greater reading difficulties under binocular viewing.The presence of oculomotor dysfunction and the extent of visual acuity and stereoacuity deficits contribute to reading difficulties in patients with amblyopia, with and without nystagmus. The understanding of reading difficulties is essential to devise accommodations to limit long-term academic and vocational consequences of amblyopia.

Diplopia is a common non-motor symptom in patients with Parkinson’s disease (PD) affecting 1/3rd of patients. We used high-resolution video-oculography to demonstrate that diplopia in PD arises from disruption of binocular co-ordination of eye movements. Using video-oculography we measured fixation eye movements, the angle and control of eye alignment and its correlation to convergence insufficiency in 13 PD patients and 6 healthy controls. We found that all PD patients had larger amplitude of fixational saccades with increased inter-saccadic drifts particularly of the non-fixing or non-viewing eye. Eye movement recordings suggest that the extent of eye alignment varies across PD subjects, 38% had good eye alignment and control under monocular and binocular viewing similar to controls (Group1). 62% of PD patients had increase in eye position difference, which was outside the threshold window of good alignment under monocular and binocular viewing (Group2 PD). PD subjects with good eye alignment were less likely to exhibit saccadic responses to disparity-driven vergence whereas those with poor control and worse eye alignment were more likely to exhibit saccadic responses with staircase saccades. A cohort of PD patients (Group2) exhibited pure vergence or combined vergence/saccade responses; they had deficits of both fusion initiating (prolonged latencies, reduced gain and peak vergence velocities) and fusion sustaining components (increased eye position variance). The results demonstrate that the vergence abnormalities in PD subjects systematically correlate with both the angle and control of eye alignment. Further, our data suggests an interaction between the vergence and saccade subsystems in PD patients. Abnormalities of vergence in PD may be the result of direct effects of the disease on vergence motor control, coupled with disturbances in the saccadic pathway indirectly leading to effects on vergence.

The variability in motor dysfunction is not uncommon in autoimmune disorders. Antibody-mediated system-wide malfunction or effects on the neural network shared by two independent pathophysiological processes can cause such heterogeneity. We tested this prediction for motor dysfunction during gaze holding in 11 patients with increased titers of glutamic acid decarboxylase (anti-GAD) antibody. High-resolution oculography measured horizontal and vertical eye positions. The analysis was performed with customized signal processing algorithms. Downbeat and gaze-evoked nystagmus commonly coexisted; one patient had a combination of upbeat and gaze-evoked nystagmus. The nystagmus was associated with saccadic intrusions in 10 patients; all had squarewaves, but five also had saccadic oscillations. The nystagmus and saccadic intrusions, both in the same axis of eye rotations, were not uncommon. Tandem appearance of the episodes of nystagmus and saccadic intrusions suggested a coupling between the two abnormalities. We speculated a unifying framework where the anti-GAD antibody inhibited (GAD mediated) conversion of glutamate to gamma-aminobutyric acid (GABA). Paucity GABA and excess of glutamate cause nystagmus (less GABA) and high-frequency saccadic oscillations (excessive glutamate).

Visual spatial dysfunction is not uncommon in Parkinson's disease. We hypothesized that visual search behavior is impaired in Parkinson's disease and the deficits correlate with changes in the amplitudes and frequency of fixational and non-fixational rapid eye movements. We measured eye movements, the horizontal and vertical angular position vectors of the right and left eye using high-resolution video oculography, in the Parkinsonian cohort who viewed a blank scene and pictures with real-life scene. Latter was associated with a task of searching an object hidden in a clutter, either at an expected or an unexpected location. Parkinsonian cohort took longer initial time to reach the region of interest. The ultimate response time was comparable in both Parkinson's disease and their healthy peers. The fixation duration was comparable in two cohorts but there was a trend wise decline for the ones located at unexpected locations. Parkinson's disease participants made more fixational saccades with significantly larger amplitude and less non-fixational saccades with significantly smaller amplitude during blank scene viewing. However, overall scanned area of the blank scene was not affected in Parkinson's disease. The Parkinson's disease participants made less non-fixational saccades with amplitudes comparable to healthy control during the visual search of a target object. Fixational saccades during visual search were larger in Parkinson's disease particularly when target was placed at an unexpected location, but the frequency was unchanged.

The syndrome of oculopalatal tremor (OPT) featuring the olivo-cerebellar hypersychrony leads to disabling pendular nystagmus and palatal myoclonus. This rare disorder provides valuable information about the motor physiology and offers insights into the mechanistic underpinning of common movement disorders. This focused review summarizes the last decade of OPT research from our laboratory and addresses three critical questions: 1) How the disease of inferior olive affects the physiology of motor learning? We discovered that our brain's ability to compensate for the impaired motor command and implement errors to correct future movements could be affected if the cerebellum is occupied in receiving and transmitting the meaningless signal. A complete failure of OPT patients to adapt to change in rapid eye movements (saccades) provided proof of this principle. 2) Whether maladaptive olivo-cerebellar circuit offers insight into the mechanistic underpinning of the common movement disorder, dystonia, characterized by abnormal twisting and turning of the body part. We discovered that the subgroup of patients who had OPT also had dystonia affecting the neck, trunk, limbs, and face. We also found that the subjects who had tremor predominant neck dystonia (without OPT) also had impaired motor learning on a long and short timescale, just like those with OPT. Altogether, our studies focused on dystonia suggested the evidence for the maladaptive olive-cerebellar system. 3) We discovered that the OPT subjects had difficulty in perceiving the direction of their linear forward motion, i.e., heading, suggesting that olivo-cerebellar hypersynchrony also affects perception.

Patients with amblyopia are known to have fixation instability, which arises from alteration of physiologic fixation eye movements (FEMs) and nystagmus. We assessed the effects of monocular, binocular, and dichoptic viewing on FEMs and eye alignment in patients with and without fusion maldevelopment nystagmus (FMN).Thirty-four patients with amblyopia and seven healthy controls were recruited for this study. Eye movements were recorded using infrared video-oculography during (1) fellow eye viewing (FEV), (2) amblyopic eye viewing (AEV), (3) both eye viewing (BEV), and (4) dichoptic viewing (DcV) at varying fellow eye (FE) contrasts. The patients were classified per the clinical type of amblyopia and FEM waveforms into those without nystagmus, those with nystagmus with and without FMN. Fixational saccades and intersaccadic drifts, quick and slow phases of nystagmus, and bivariate contour ellipse area were analyzed in the FE and amblyopic eye (AE).We found that FEMs are differentially affected with increased amplitude of quick phases of FMN observed during AEV than BEV and during DcV at lower FE contrasts. Increased fixation instability was seen in anisometropic patients at lower FE contrasts. Incomitance of eye misalignment was seen with the greatest increase during FEV. Strabismic/mixed amblyopia patients without FMN were more likely to demonstrate a fixation switch where the AE attends to the target during DcV than patients with FMN.Our findings suggest that FEM abnormalities modulate with different viewing conditions as used in various amblyopia therapies. Increased FEM abnormalities could affect the visual function deficits and may have treatment implications.

Video stream: https://vimeo.com/365522806 The human ability for visualization extends far beyond the physical items that surround us. We are able to dismiss the constant influx of photons hitting our retinas, and instead picture the layout of our kindergarten classroom, envision the gently swaying palm trees of our dream vacation, or foresee the face of a yet-to-be-born child. As we inspect imaginary objects and people with our mind’s eye, our corporeal eyeballs latch onto the fantasy. Research has found that our eyes can move as if seeing, even when there is nothing to look at. Thus, gaze explorations in the absence of actual vision have been reported in many contexts, including in visualization and memory tasks, and perhaps even during REM sleep. This symposium will present the manifold aspects of gaze dynamics in conditions when the visual input is impoverished or altogether absent. Presentations will address the characteristics of large and small eye movements during imagined and remembered scenes, the impact of visual field deficits on oculomotor control, and the role of eye movements in the future development of neural prosthetics for the blind.

Visuomotor impairments, such as hypometria of visually guided saccades, are common in Parkinson's disease (PD). Explaining the mechanistic underpinning of such abnormal voluntary (eye) movements can provide insights into the pathophysiology of limb movement disorders in PD. We measured visually guided saccades in 20 PD patients using quantitative high-resolution oculography. The experiments source to determine whether common motor deficits in PD, such as those affecting visually-guided saccades reflect excessive inhibition of the superior colliculus or rather involvement of brainstem saccade generators. We found slowing, interruptions, and curvatures in the saccade trajectory. The curvature not only reflected the mismatch in the velocity of relatively slower vertical (compared to horizontal) saccades, but could be due to aberrant activation of the superior colliculus. The irregularities in the saccade trajectory and slowing were prominent in the vertical direction. We suggest that abnormal saccades in PD not only reflect abnormal tectal function, but also suggest abnormal oscillatory behavior in the reciprocally innervating circuit of excitatory and inhibitory burst neurons. Impaired function of excitatory and inhibitory burst neurons causing maladaptive feedback and premature activation of the superior colliculus can cause irregularity in saccade trajectory.

Fixational eye movements comprise of fast microsaccades alternating with slow inter-saccadic drifts. These physiologic eye movements play an important role in visual perception. Amblyopic patients are known to have fixation instability, particularly of the amblyopic eye. We examined eye movement abnormalities that contribute to this instability. We found that fixation stability is affected by the presence of fusion maldevelopment nystagmus (FMN). However, some amblyopes can have nystagmus without nasally directed slow phases and reversal in direction of the quick phase on ocular occlusion, features seen in FMN. In patients without nystagmus, we found increased amplitude of fixational saccades and inter-saccadic drifts. We categorized amblyopia patients by type (anisometropic, strabismic, or mixed) and eye movement waveform (no nystagmus, nystagmus without FMN, and FMN). We found specific fast and slow eye movement abnormalities of the fellow and amblyopic eye during fellow, amblyopic and both eyes viewing conditions across eye movement waveforms and types of amblyopia. These eye movement abnormalities can serve as biomarkers that can predict the impact of amblyopia as measured by visual acuity and stereopsis. Evaluation of fixational eye movements in amblyopia could be important to diagnose these common eye diseases and predict treatment effectiveness.

Objective: Parkinson's disease (PD) frequently affects vergence eye movements interfering with the perception of depth and dimensionality critical for mitigating falls. We examined neural strategies that compensate for abnormal vergence and their mechanistic underpinning in PD.Approach:Thea priorihypothesis was that impaired vergence is compensated by incorporating rapid eye movements (saccades) to accomplish gaze shifts at different depths. Our experiments examined the hypothesis by simulating biologically plausible computational models of saccade-vergence interactions in PD and validating predictions in the actual patient data.Main results:We found four strategies to accomplish 3D gaze shift; pure vergence eye movements, pure saccadic eye movements, combinations of vergence followed by a saccade, and combination of saccade followed by vergence. The gaze shifting strategy of the two eyes was incongruent in PD. The latency of vergence was prolonged, and it was more so when the saccades preceded the vergence or when the saccades only made 3D gaze shift. Computational models predicted at least two possible mechanisms triggering saccades along with vergence. One is based on the lack of foveal accuracy when the vergence gain is suboptimal. The second mechanism reflects the noise in the gating mechanism, the omnipause neurons, for vergence and saccades. None of the two model predictions alone were completely supported by the patient data. However, a combined model incorporating both abnormal vergence velocity gain and impaired gating accurately simulated the results from PD patients.Significance:The combined strategy is biologically plausible for two reasons: (a) The basal ganglia that is prominently affected in PD projects to the vergence velocity neurons in the midbrain via the cerebellum. The projection directly affects the vergence velocity gain. (b) The basal ganglia, via superior colliculus, influences the pattern of omnipause neuronal activity. Abnormal basal ganglia activity may introduce noise in the omnipause neurons.

Purpose We investigated how the abnormalities of fixation eye movements (FEMs) of the amblyopic eye were linked with treatment outcomes following part-time patching therapy in children with amblyopia. Methods We recruited 53 patients, with at least 12 months of patching, and measured FEMs at the end of treatment. Subjects were classified based on FEM waveforms (those without nystagmus = 21, those with nystagmus without fusion maldevelopment nystagmus (FMN) = 21, and those with FMN = 11) and based on clinical type of amblyopia (anisometropic = 18, strabismic = 6, and mixed = 29). The treatment outcomes such as duration of treatment of receiving part-time patching therapy, visual acuity and stereo-acuity deficits at the end of treatment were determined. Bivariate contour ellipse area (BCEA), fast (fixational saccade/quick phases), and slow (inter-saccadic drifts/slow phases) FEMs of the fellow and amblyopic eye were analyzed. Results Anisometropic group had less residual amblyopia (0.23±0.19logMAR acuity) compared to strabismic/mixed (0.36±0.26) groups (p = 0.007). Treatment duration in patients without nystagmus was lower (12.6±9.5months) compared to nystagmus without FMN (25.6±23.2) and FMN (29.5±20.4) groups (p = 0.006). Patients without nystagmus had better stereopsis at the end of treatment (2.3±0.84logarcsecs) compared to nystagmus without FMN (2.6±0.84) group (p = 0.003). The majority of patients with FMN (8/11) had absent stereopsis. BCEA of the amblyopic eye was higher in patients with greater residual visual acuity deficits in patients without nystagmus. No such association was seen in Nystagmus no FMN and FMN groups. Increased amplitude of fast FEMs, increased eye position variance and eye velocity of slow FEMs were seen in patients who had received longer duration of part time patching therapy and in those with greater residual amblyopia, and poor stereopsis at the end of treatment. Conclusions Assessment of FEM waveforms and fast and slow FEM characteristics are important measures while describing fixation instability in amblyopia. Several FEM abnormalities were associated with stereo-acuity and visual acuity deficits and treatment duration in patients with amblyopia treated with part time patching therapy.

Pattern strabismus is a vertically incomitant horizontal strabismus comprising 50% of its infantile forms. High-resolution orbit imaging and contemporary physiology literature suggested the role of oblique muscle dysfunction as its pathophysiology. The role of the central nervous system was also outlined. Here, we will discuss contemporary theories with specific focus on pathophysiological concepts including oblique muscle dysfunction, loss of fusion with altered recti muscle pull, displacements and instability in connective tissue pulleys of the recti muscles, vestibular hypofunction, and abnormal neural connections.

Amblyopic patients are known to have fixation instability, particularly of the amblyopic eye. The stability of the fixation is affected by the presence of nystagmus, the frequency and amplitude of fixational saccades and inter-saccadic drifts. Amblyopic patients without nystagmus have increased amplitude of the fixational saccades with reduced frequency of the physiologic microsaccades and have increased inter-saccadic drifts. Amblyopia patients who have experienced a disruption in binocularity in early infancy develop fusion maldevelopment nystagmus (FMN) previously called latent nystagmus as it is more evident during monocular viewing conditions. We have found that some amblyopic patients can have nystagmus with slow phases that are not directed nasally and without the reversal in direction on ocular occlusion, features seen in patients with FMN. The current mainstay of amblyopia treatment comprises of part-time occlusion therapy of the non- amblyopic eye. The amount of patching treatment is in the range of 2-6 hours/day as determined by the severity of amblyopia. Despite treatment, up to 40% of patients have residual amblyopia. We analyzed the effectiveness of part-time occlusion therapy in amblyopic patients as a function of fixation instability. We categorized amblyopic patients based on their eye movement waveforms obtained during a visual fixation task into those lacking nystagmus, those with FMN and those with nystagmus but no FMN. We did a retrospective chart review to gather information about their clinical characteristics and treatment response. We found that patients with FMN require a more prolonged duration of treatment and have a poorer recovery of stereopsis compared to patients with nystagmus but no FMN and patients lacking nystagmus. This study suggests that eye movement assessment provides valuable information in the management of amblyopia.

Visuomotor impairments, such as hypometria of visually guided saccades, are common in Parkinson's disease (PD). Explaining the mechanistic underpinning of such abnormal voluntary (eye) movements can provide insights into the pathophysiology of limb movement disorders in PD. We measured visually guided saccades in 20 PD patients using quantitative high-resolution oculography. The experiments source to determine whether common motor deficits in PD, such as those affecting visually-guided saccades reflect excessive inhibition of the superior colliculus or rather involvement of brainstem saccade generators. We found slowing, interruptions, and curvatures in the saccade trajectory. The curvature not only reflected the mismatch in the velocity of relatively slower vertical (compared to horizontal) saccades, but could be due to aberrant activation of the superior colliculus. The irregularities in the saccade trajectory and slowing were prominent in the vertical direction. We suggest that abnormal saccades in PD not only reflect abnormal tectal function, but also suggest abnormal oscillatory behavior in the reciprocally innervating circuit of excitatory and inhibitory burst neurons. Impaired function of excitatory and inhibitory burst neurons causing maladaptive feedback and premature activation of the superior colliculus can cause irregularity in saccade trajectory.

Purpose Microsaccades shift the image on the fovea and counteract visual fading. They are also thought to serve as an optimal sampling strategy while viewing complex visual scenes. The goal of our study was to assess visual search in amblyopic children. Methods Twenty-one amblyopic children with varying severity of amblyopia and 10 healthy controls were recruited. Eye movements were recorded using infrared video-oculography during amblyopic and fellow eye viewing while the subjects performed (1) visual fixation, (2) exploration of a blank scene, and (3) visual search task (spot the difference between two images). The number of correctly identified picture differences and reaction time were recorded. Microsaccade, saccades, and intersaccadic drifts were analyzed in patients without latent nystagmus (LN). Slow phase velocities were computed for patients with LN. Results Both patients with and without LN were able to spot the same number of differences but took longer during fellow eye viewing compared to controls. The ability to identify differences was diminished during amblyopic eye viewing particularly those with LN and severe amblyopia. We found reduced frequencies of microsaccades and saccades in both amblyopic and fellow eyes during fixation and visual search but not during exploration of blank scene. Across all tasks, amblyopes with LN had increased intersaccadic drifts. Conclusions Our findings suggest that deficient microsaccade and saccadic activity contributes to poorer sampling strategy in amblyopia, which is seen in both amblyopic and fellow eye. These deficits are more notable among subjects who experienced binocular decorrelation earlier in life, with subsequent development of LN.

We describe novel deficits of gaze holding and ocular alignment in patients with spinocerebellar ataxia type 3, also known as Machado-Joseph disease (MJD). Twelve MJD patients were studied. Clinical assessments and quantitative ocular alignment measures were performed. Eye movements were quantitatively assessed with corneal curvature tracker and video-oculography. Strabismus was seen in ten MJD patients. Four patients had mild to moderate intermittent exotropia, three had esotropia, one had skew deviation, one had hypotropia, and one patient had moderate exophoria. Three strabismic patients had V-pattern. Near point of convergence was normal in two out of three patients with exotropia. Gaze holding deficits were also common. Eight patients had gaze-evoked nystagmus, and five had micro-opsoclonus. Other ocular motor deficits included saccadic dysmetria in eight patients, whereas all had saccadic interruption of smooth pursuit. Strabismus and micro-opsoclonus are common in MJD. Coexisting ophthalmoplegia or vergence abnormalities in our patients with exotropia that comprised 50 % of the cohort could not explain the type of strabismus in our patients. Therefore, it is possible that involvement of the brainstem, the deep cerebellar nuclei, and the superior cerebellar peduncle are the physiological basis for exotropia in these patients. Micro-opsoclonus was also common in MJD. Brainstem and deep cerebellar nuclei lesion also explains micro-opsoclonus, whereas brainstem deficits can describe slow saccades seen in our patients with MJD.

Chiari malformation is a congenital deformity leading to herniation of cerebellar tonsils. Headache is a typical symptom of this condition, but patients with Chiari malformation often present with double vision and vertigo. Examination of eye movements in such patients often reveals nystagmus and strabismus. Eye movement deficits in the context of typical symptomatic presentation are critical clinical markers for the diagnosis of Chiari malformation. We will review eye movement deficits that seen in patients with type 1 Chiari malformation. We will then discuss the underlying pathophysiology and therapeutic options for such deficits.

To determine the reproducibility of spectral-domain optical coherence tomography (OCT) measurements of peripapillary retinal nerve fiber layer (RNFL) and macular retinal thickness of the central 20-degree area of the posterior pole in adult and pediatric glaucoma and normal subjects.Prospective.Normal, glaucoma suspect and glaucoma eyes of adult and pediatric subjects were recruited. Spectralis OCT scans were obtained 3 times on the same day (intravisit) and 4 weeks later (intervisit). Six individual sectors, average RNFL, and macular retinal thickness using an 8×8 mm grid centered on the foveal pit were measured for all the eyes. The central 16 square areas centered on the foveal pit were called the central macular area and the surrounding 48 square areas were called the perimacular area. Intraclass correlation coefficient, coefficient of variation (COV), and test-retest variability were calculated.Included were 51 adult eyes and 25 pediatric eyes. The intravisit and intervisit intraclass correlation coefficient for the central macular, perimacula, and average RNFL was very good (0.8) for all adult and pediatric normal and glaucomatous eyes. The mean COVs of normal and glaucomatous eyes were higher for average RNFL (1.5 ± 1.5% adults, 1.0 ± 0.9% pediatric) compared to the central macula (0.56 ± 0.54% adults, 0.68 ± 0.64% pediatric) and perimacular thickness (0.64 ± 0.51% adults, 0.57 ± 0.42% pediatric) (1-way analysis of variance, P0.05). No difference was noted in the intravisit and intervisit COVs between the adult and pediatric eyes of central macula, perimacula, and average RNFL thickness (unpaired t test, P0.05). No intervisit reproducibility analysis was available for pediatric glaucoma eyes.The reproducibility of Spectralis spectral-domain-OCT were very good for both RNFL and macular thickness measurements in glaucoma/glaucoma suspect eyes of adult and pediatric subjects.

Discovery of inter-latching circuits in the basal ganglia and invention of deep brain stimulation (DBS) for their modulation is a breakthrough in basic and clinical neuroscience. The DBS not only changes the quality of life of hundreds of thousands of people with intractable movement disorders, but it also offers a unique opportunity to understand how the basal ganglia interacts with other neural structures. An attractive yet less explored area is the study of DBS on eye movements and vestibular function. From the clinical perspective such studies provide valuable guidance in efficient programming of stimulation profile leading to optimal motor outcome. From the scientific standpoint such studies offer the ability to assess the outcomes of basal ganglia stimulation on eye movement behavior in cognitive as well as in motor domains. Understanding the influence of DBS on ocular motor function also leads to analogies to interpret its effects on complex appendicular and axial motor function. This review focuses on the influence of globus pallidus, subthalamic nucleus, and thalamus DBS on ocular motor and vestibular functions. The anatomy and physiology of basal ganglia, pertinent to the principles of DBS and ocular motility, is discussed. Interpretation of the effects of electrical stimulation of the basal ganglia in Parkinson's disease requires understanding of baseline ocular motor function in the diseased brain. Therefore we have also discussed the baseline ocular motor deficits in these patients and how the DBS changes such functions.

Eye position-sensitive neurons are found in parietooccipital and anterior-inferior temporal cortex. Putative role of these neurons is to facilitate transformation of reference frame from the retina-fixed to world-fixed coordinates and assure precise action. We assessed the nature of ocular motor disorder in a subject who had selective resection of the right anterior-inferior temporal cortex for the treatment of intractable epilepsy from cortical dysplasia. The gaze was stable when the subject was viewing straight-ahead, but centrally directed drifts in the eye position were seen during eccentric horizontal gaze holding. Eye-in-orbit position determined drift velocity and its direction. Conjugate and sinusoidal vertical oscillations were also present. Horizontal drifts and vertical oscillations became prominent and disconjugate in the absence of visual cue. The gaze-holding deficit was consistent with impairment in neural integration, but in the absence of cerebellar and visual deficits. We speculate that brainstem neural integrator might receive cortical feedback regarding world-fixed coordinates. Visual system might calibrate this process. Hence the lesion of the anterior-inferior temporal lobe leads to impairment in the function of neural integrator. Vision might be used to calibrate such feedback, hence the lack of visual cue further impairs the function of the neural integrator leading to worsening of gaze-holding deficits.

Spectral-domain (SD)- Optical Coherence Tomography (OCT) can track eye movements, has faster acquisition time and higher resolution than time-domain(TD)-OCT. The aim of the study was to assess the utility of SD-OCT in paediatric glaucoma and determine its agreement with TD-OCT.Children who had SD-OCT(Spectralis, Heidelberg-Engineering,Germany) were retrospectively and prospectively identified from Duke paediatric glaucoma clinic. The peripapillary retinal nerve fibre layer (RNFL) and macular thickness and volume (MV) were compared amongst four groups: normal eyes, eyes with physiologic cupping (C:D0.5 and0.8, IOP21), mild glaucomatous eyes (C:D0.5, intra-ocular pressure (IOP)21) and severe glaucoma (C:D0.5, IOP21). SD-OCT values were compared to TD-OCT(OCT-3, Carl-Zeiss-Meditec, Dublin, CA) values in a subset of subjects who had same day scans using both instruments. Children with neurologic disorders, refractive error±5D, pseudophakia and prematurity were excluded.Included were 83 eyes of 83 children, mean age 11.9 ± 4.2 years. SD-OCT measurements of average RNFL thickness and MV differed among normals(n=24), physiologically cupped (n=31), mild (n=15) versus severe glaucoma (n=13): (RNFL:104 ± 9, 99 ± 6, 98 ± 9 vs 62 ± 18 µm, respectively, p0.05; MV: 8.7 ± 0.3, 8.6 ± 0.3, 8.8 ± 0.4 vs 8.0 ± 0.6 mm³;, respectively, p0.05). Same-day SD-OCT and TD-OCT measures in 53 eyes correlated linearly (RNFL r(2)=0.88; MVr(2)=0.58). SD-OCT measured lower RNFL and higher macular thickness than TD-OCT. Among eyes with severe glaucoma, 4 of 13 (30%) had unreliable TD-OCT but reliable SD-OCT.SD-OCT was easier to obtain than TD-OCT in children. SD-OCT and TD-OCT measurements correlated, but values were not interchangeable.

IntroductionFixational saccades are miniature eye movements that constantly change the gaze during attempted visual fixation. Visually guided saccades and fixational saccades represent an oculomotor continuum and are produced by common neural machinery. Patients with strabismus have disconjugate binocular horizontal saccades. We examined the stability and variability of eye position during fixation in patients with strabismus and correlated the severity of fixational instability with strabismus angle and binocular vision.MethodsEye movements were measured in 13 patients with strabismus and 16 controls during fixation and visually guided saccades under monocular viewing conditions. Fixational saccades and intersaccadic drifts were analysed in the viewing and non-viewing eye of patients with strabismus and controls.ResultsWe found an increase in fixational instability in patients with strabismus compared with controls. We also found an increase in the disconjugacy of fixational saccades and intrasaccadic ocular drift in patients with strabismus compared with controls. The disconjugacy was worse in patients with large-angle strabismus and absent stereopsis. There was an increase in eye position variance during drifts in patients with strabismus. Our findings suggest that both fixational saccades and intersaccadic drifts are abnormal and likely contribute to the fixational instability in patients with strabismus.DiscussionFixational instability could be a useful tool for mass screenings of children to diagnose strabismus in the absence of amblyopia and latent nystagmus. The increased disconjugacy of fixational eye movements and visually guided saccades in patients with strabismus reflects the disruption of the fine-tuning of the motor and visual systems responsible for achieving binocular fusion in these patients.

Purpose Fixational eye movements are of particular interest for three reasons. They are critical for preventing visual fading and enhancing visual perception; their disconjugacy allows scanning in three dimensions, and their neural correlates span through the cortico-striatal, striato-collicular and brainstem networks. Fixational eye movements are altered in various pediatric ophthalmologic and neurologic disorders. The goal of this study was to compare the dynamics of fixational eye movements in normal children and adults. Methods We measured the fixational saccades and inter-saccadic drifts in eye positions using infrared video-oculography in children and adults. We assessed the frequency, amplitude, main-sequence, and disconjugacy of fixational saccades as well as the intra-saccadic drift velocity and variance between these two groups. Results We found a similar frequency but an increase in the amplitude of fixational saccades in children compared to adults. We also found that the fixational saccades were more conjugate in children than in adults. The inter-saccadic drifts were comparable between the two groups. Discussion This study provides normative values of dynamics of fixational eye movement in children and adults. The greater disconjugacy of fixational saccades in adults suggests the existence of neural mechanisms that can independently regulate the movements of two eyes. The differences between adult and pediatric populations could be due to completion of the development of binocularly independent regulation of fixational saccades nearing adulthood. The alternate possibility is that the increased disconjugacy between the two eyes may represent a deficiency in the eye movement performance as a function of increasing age.