Eight-Year Outcomes of Bilateral Lateral Rectus Recessions versus Unilateral Recession-Resection in Childhood Basic-Type Intermittent Exotropia.

PURPOSE: To report 8-year outcomes from a randomized controlled trial (RCT) comparing bilateral lateral rectus muscle recession (BLRc) with unilateral recession-resection (R&R) for childhood intermittent exotropia (IXT). DESIGN: Eight-year follow-up of RCT cohort. PARTICIPANTS: Of 197 randomized participants, 123 agreed to continue follow-up after the 3-year outcome visit (baseline age, 3-< 11 years; basic-type IXT, 15-40 prism diopters [Δ] by prism and alternate cover test [PACT]; baseline stereoacuity, ≤ 400 arcsec; no prior surgery). METHODS: After the RCT primary outcome at 3 years, annual follow-up from 4 through 8 years with treatment at investigator discretion. MAIN OUTCOME MEASURES: Suboptimal surgical outcome by 8 years after randomization, defined as any of the following at any visit: exotropia of 10 Δ or more by simultaneous prism cover test (SPCT) at distance or near, constant esotropia (ET) of 6 Δ or more by SPCT at distance or near, loss of near stereoacuity by 0.6 log arcsec or more from baseline, or reoperation. Secondary outcomes included (1) reoperation by 8 years and (2) complete or near-complete resolution at 8 years, defined as exodeviation of less than 10 Δ by SPCT and PACT at distance and near and 10 Δ or more reduction from baseline by PACT at distance and near, ET of less than 6 Δ at distance and near, no decrease in stereoacuity by 0.6 log arcsec or more from baseline, and no reoperation or nonsurgical treatment for IXT. RESULTS: The Kaplan-Meier cumulative probability of suboptimal surgical outcome through 8 years was 68% (55 events among 101 at risk) for BLRc and 53% (42 events among 96 at risk) for R&R (difference, 15%; 95% confidence interval [CI], -2% to 32%; P = 0.08). Complete or near-complete resolution at 8 years occurred in 15% (7/46) for BLRc and 37% (16/43) for R&R (difference, -22%; 95% CI, -44% to -0.1%; P = 0.049). The cumulative probability of reoperation was 30% for BLRc and 11% for R&R (difference, 19%; 95% CI, 2%-36%; P = 0.049). CONCLUSIONS: Despite no significant difference for the primary outcome, the 95% CI did not exclude a moderate benefit of R&R, which together with secondary outcomes suggests that unilateral R&R followed by usual care may yield better long-term outcomes than BLRc followed by usual care for basic-type childhood IXT using these surgical doses. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Navigating Visual Challenges: How Parkinson's Disease Alters Cognitive Priorities in Visual Search.

OBJECTIVE: Parkinson's disease (PD) hampers visual search tasks such as reading, driving, and navigation. We examined expectations from past experiences, guiding cognition and contextual priors, on visual search in PD. METHODS: We compared eye movements as PD and healthy participants searched for a hidden object (target) in cluttered real-world scenes. RESULTS: PD participants prolonged fixation on high-probability (high-prior) locations for the target, consistent across expected and unexpected scenario. Such emphasis on contextual visual priors, evidenced by high fixation duration on high-probability areas, was beneficial when the target was at the expected location but presented challenges when the target was situated in an unlikely place. CONCLUSION: This study contributes to understanding how PD impacts visual search behavior and cognitive processing. The findings indicate that PD alters attention allocation and visual processing by affecting the utilization of contextual visual priors. It provides insights for potential interventions targeting visuo-cognitive deficits in PD patients. Published 2024. This article is a U.S. Government work and is in the public domain in the USA.

Gaze-holding and anti-GAD antibody: prototypic heterogeneous motor dysfunction in immune disease.

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).

Temporal Patterns of Spontaneous Fixational Eye Movements: The Influence of Basal Ganglia.

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.

Lessons learned from the syndrome of oculopalatal tremor.

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.

Effects of subthalamic deep brain stimulation on fixational eye movements in Parkinson's disease.

Miniature yoked eye movements, fixational saccades, are critical to counteract visual fading. Fixational saccades are followed by a return saccades forming squarewaves. Present in healthy states, squarewaves, if too many or too big, affect visual stability. Parkinson's disease (PD), where visual deficits are not uncommon, is associated with the squarewaves that are excessive in number or size. Our working hypothesis is that the basal ganglia are at the epicenter of the abnormal fixational saccades and squarewaves in PD; the effects are manifested through their connections to the superior colliculus (affecting saccade frequency and amplitude) and the cerebellum (affecting velocity and amplitude). We predict that the subthalamic deep brain stimulation (DBS) variably affects the amplitude, frequency, and velocity of fixational saccade and that the effect depends on the electrode's proximity or the volume of activated tissue in the subthalamic nucleus' connections with the superior colliculus or the cerebellum. We found that DBS modulated saccade amplitude, frequency, and velocity in 11 PD patients. Although all three parameters were affected, the extent of the effects varied amongst subjects. The modulation was dependent upon the location and size of the electrically activated volume of the subthalamic region.

Consensus on Virtual Management of Vestibular Disorders: Urgent Versus Expedited Care.

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.

Effects of Parkinson Disease on Blur-Driven and Disparity-Driven Vergence Eye Movements.

ABSTRACT: Synchronous movements of the 2 eyes in the opposite direction, disconjugate movements such as vergence, facilitate depth perception. The vergence eye movements are affected in Parkinson disease (PD). Visual blur (accommodation) and fusion (retinal disparity) are important triggers for the vergence. The neural circuit responsible for blur-driven and disparity-driven vergence is tightly coupled. We investigated the effect of PD on these 2 vergence paradigms. In the experiment involving 14 patients with PD and 6 healthy controls, substantial differences between blur-driven and disparity-driven vergence were found. The gain (ratio of actual vs desired eye movements) was reduced in patients with PD in case of disparity-driven vergence but not in blur-driven vergence. The latency of disparity-driven vergence onset was significantly longer for patients with PD compared with healthy controls. Four strategies were used to drive disparity-driven vergence: a) pure disconjugate vergence, b) conjugate saccadic movements, c) disconjugate vergence followed by saccadic movements, and d) conjugate saccades followed by disconjugate vergence movements. Blur-driven vergence had only 2 strategies: a) conjugate saccades followed by disconjugate vergence and b) conjugate saccadic movements only. The results are consistent with the prediction that PD primarily affects disparity-driven vergence, but there are some effects on the strategies to execute blur-driven vergence. We speculate that the deep cerebellar nuclei and the supraoculomotor area of the midbrain that carry the disparity-driven and blur-driven vergence are affected in PD. It is possible to modulate their function through projections to the subthalamic nuclei.

Strabismus and Micro-Opsoclonus in Machado-Joseph Disease.

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.

Experimental tests of hypotheses for microsaccade generation.

Fixational eye movements such as microsaccades are important to prevent fading. These miniature eye movements are also necessary to redirect gaze to the target after a drift. Generation of saccades and microsaccades utilizes common neural substrates. We, therefore, hypothesized that physiological modulators of saccades should also affect microsaccades. Test of this hypothesis will also provide support for the models of a microsaccade generation. We performed two experiments. In the first experiment, complete darkness led to a decrease in the frequency and velocity, but increased the amplitude of microsaccades. In the second experiment, active eyelid closure further reduced the velocity and frequency of microsaccades, but increased their amplitude. Darkness reduces the superior colliculus activity leading to a reduction in the velocity and frequency of microsaccades. Eye closure might cause sustained inhibition of the omnipause neurons. Subsequent disinhibition of the burst neurons might cause a reduction in the post-inhibitory rebound firing resulting in a decreased velocity of microsaccades. Sustained inhibition of the omnipause neurons could also reduce the inhibitory drive that would otherwise abort microsaccades. Hence, by inhibiting the activity of omnipause neurons, the eye closure could increase the amplitude of microsaccades.

Source of high-frequency oscillations in oblique saccade trajectory.

Most common eye movements, oblique saccades, feature rapid velocity, precise amplitude, but curved trajectory that is variable from trial-to-trial. In addition to curvature and inter-trial variability, the oblique saccade trajectory also features high-frequency oscillations. A number of studies proposed the physiological basis of the curvature and inter-trial variability of the oblique saccade trajectory, but kinematic characteristics of high-frequency oscillations are yet to be examined. We measured such oscillations and compared their properties with orthogonal pure horizontal and pure vertical oscillations generated during pure vertical and pure horizontal saccades, respectively. We found that the frequency of oscillations during oblique saccades ranged between 15 and 40 Hz, consistent with the frequency of orthogonal saccadic oscillations during pure horizontal or pure vertical saccades. We also found that the amplitude of oblique saccade oscillations was larger than pure horizontal and pure vertical saccadic oscillations. These results suggest that the superimposed high-frequency sinusoidal oscillations upon the oblique saccade trajectory represent reverberations of disinhibited circuit of reciprocally innervated horizontal and vertical burst generators.

Gaze holding after anterior-inferior temporal lobectomy.

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.

A 360° View for Large Language Models: Early Detection of Amblyopia in Children using Multi-View Eye Movement Recordings.

Amblyopia is a neurodevelopmental visual disorder that affects approximately 3-5% of children globally and it can lead to vision loss if it is not diagnosed and treated early. Traditional diagnostic methods, which rely on subjective assessments and expert interpretation of eye movement recordings presents challenges in resource-limited eye care centers. This study introduces a new approach that integrates the Gemini large language model (LLM) with eye-tracking data to develop a classification tool for diagnosis of patients with amblyopia. The study demonstrates: (1) LLMs can be successfully applied to the analysis of fixation eye movement data to diagnose patients with amblyopia; and (2) Input of medical subject matter expertise, introduced in this study in the form of medical expert augmented generation (MEAG), is an effective adaption of the generic retrieval augmented generation (RAG) approach for medical applications using LLMs. This study introduces a new multi-view prompting framework for ophthalmology applications that incorporates fine granularity feedback from pediatric ophthalmologist together with in-context learning to report an accuracy of 80% in diagnosing patients with amblyopia. In addition to the binary classification task, the classification tool is generalizable to specific subpopulations of amblyopic patients based on severity of amblyopia, type of amblyopia, and with or without nystagmus. The model reports an accuracy of: (1) 83% in classifying patients with moderate or severe amblyopia, (2) 81% in classifying patients with mild or treated amblyopia; and (3) 85% accuracy in classifying patients with nystagmus. To the best of our knowledge, this is the first study that defines a multi-view prompting framework with MEAG to analyze eye tracking data for the diagnosis of amblyopic patients.

Monitoring Eye Movement in Patients with Parkinson's Disease: What Can It Tell Us?

Parkinson's disease (PD) affects approximately 10 million individuals worldwide. Visual impairments are a common feature of PD. Patients report difficulties with visual scanning, impaired depth perception and spatial navigation, and blurry and double vision. Examination of PD patients reveals abnormal fixational saccades, strabismus, impaired convergence, and abnormal visually-guided saccades. This review aims to describe objective features of abnormal eye movements in PD and to discuss the structures and pathways through which these abnormalities may manifest.

Objective assessment of eye alignment and disparity-driven vergence in Parkinson's disease.

Background: Self-reported diplopia is described in up to one-third of Parkinson's disease (PD) patients. Objective: The purpose of our study was to expand our understanding of the mechanistic underpinnings of diplopia in PD. We hypothesize that the time-based control of eye alignment and increased eye deviation under binocular viewing will be related to the fusion-initiating and fusion-maintaining component deficits of disparity-driven vergence in PD. Methods: We used high-resolution video-oculography to measure eye alignment under binocular and monocular viewing and disparity-driven vergence in 33 PD and 10 age-matched healthy participants. We computed eye deviation and time-based control of eye alignment, occurrence of conjugate saccadic eye movements, latency and gain of vergence (fusion initiation), and variance of eye position at the end of dynamic vergence (fusion maintenance). Results: We categorized PD subjects into three groups, considering their time-based control of eye alignment as compared to healthy controls in binocular viewing. Group 1 = 45% had good control and spent >80% of the time when the eyes were well-aligned, Group 2 = 26% had intermediate control and spent <80% but greater >5% of the time when the eyes were well-aligned, and Group 3 = 29% had very poor control with increased eye deviation majority of the times (<5% of the time when the eyes were well-aligned). All three groups exhibited greater eye deviation under monocular viewing than controls. PD subjects exhibited fusion-initiating and fusion-maintaining vergence deficits (prolonged latencies, reduced vergence gain, increased variance of fusion-maintaining component) with a greater probability of saccadic movements than controls. Group 2 and Group 3 subjects were more likely to exhibit failure to initiate vergence (>20%) than Group 1 (13%) and controls (0%) trials. No significant difference was found in the Unified Parkinson's Disease Rating Scale (UPDRS-a tool to measure the severity of PD) values between the three PD groups (Group 1 = 33.69 ± 14.22, Group 2 = 38.43 ± 22.61, and Group 3 = 23.44 ± 1, p > 0.05). Conclusion: The majority of PD subjects within our cohort had binocular dysfunction with increased eye deviation under monocular viewing and disparity-driven vergence deficits. PD subjects with intermediate or poor control of eye deviation under binocular viewing had greater fusion-initiating and fusion-maintaining vergence deficits. The study highlights the importance of assessing binocular dysfunction in PD subjects independent of the severity of motor symptoms.

Eye movements in Parkinson's disease during visual search.

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.

Effect of Viewing Conditions on Fixation Eye Movements and Eye Alignment in Amblyopia.

Purpose: 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). Methods: 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). Results: 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. Conclusions: 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.

Reading difficulties in amblyopia: Consequence of visual sensory and oculomotor dysfunction.

INTRODUCTION: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Computational models to delineate 3D gaze-shift strategies in Parkinson's disease.

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.