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1.
medRxiv ; 2024 May 10.
Article En | MEDLINE | ID: mdl-38765973

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.

2.
Invest Ophthalmol Vis Sci ; 65(3): 19, 2024 Mar 05.
Article En | MEDLINE | ID: mdl-38470326

Purpose: Amblyopic and strabismus subjects experience inter-ocular suppression, impaired stereoacuity, and increased fixation instability. The purpose of the study was to investigate factors affecting suppression and stereoacuity and examine their relationship to fixation eye movement (FEM) abnormalities. Methods: We recruited 14 controls and 46 amblyopic subjects (anisometropic = 18, strabismic = 14, and mixed = 14) and 11 subjects with strabismus without amblyopia. We utilized the dichoptic motion coherence test to quantify suppression, and stereoacuity was assessed using the Titmus Fly test. We recorded FEMs using high-resolution video-oculography and classified subjects that did not have nystagmus (n = 27) versus those with nystagmus (n = 32; fusion maldevelopment nystagmus [FMN], n = 10) and nystagmus that did not meet the criteria of FMN (n = 20). We also recorded FEMs under dichoptic viewing (DcV) at varied fellow eye (FE) contrasts and computed the amplitude and velocity of the fast and slow FEMs and vergence instability. Results: Inter-ocular suppression and stereoacuity deficits were closely correlated with an amblyopic eye (AE), visual acuity, and strabismus angle. Subjects with nystagmus displayed more pronounced stereoacuity deficits than those without nystagmus. Strabismic subjects with and without amblyopia, who demonstrated a fixation switch at 100% FE contrast, had lower inter-ocular suppression than subjects lacking a fixation switch under DcV. Amplitude of fast FEMs and velocity of slow FEMs, and vergence instability were increased as the FE contrast was lowered in both amblyopic and strabismic subjects. Conclusions: The current study highlights the intricate relationships between AE visual acuity, eye deviation, and FEM abnormalities on suppression and stereoacuity deficits and underscores the need to evaluate FEM abnormalities while assessing dichoptic treatment outcomes.


Amblyopia , Strabismus , Humans , Eye Movements , Eye , Visual Acuity
3.
Ophthalmology ; 131(1): 98-106, 2024 Jan.
Article En | MEDLINE | ID: mdl-37696452

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.


Esotropia , Exotropia , Humans , Child , Exotropia/surgery , Follow-Up Studies , Oculomotor Muscles/surgery , Ophthalmologic Surgical Procedures , Visual Acuity , Chronic Disease , Esotropia/surgery , Treatment Outcome , Retrospective Studies , Vision, Binocular/physiology
4.
Front Aging Neurosci ; 15: 1217765, 2023.
Article En | MEDLINE | ID: mdl-38020777

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.

5.
Eye Brain ; 15: 101-112, 2023.
Article En | MEDLINE | ID: mdl-37519412

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.

6.
J Neurol Sci ; 451: 120721, 2023 08 15.
Article En | MEDLINE | ID: mdl-37433244

INTRODUCTION: Visual function deficits are seen in amblyopic subjects during fellow and binocular viewing. The purpose of the study was to examine the relationship between Fixation Eye Movement (FEM) abnormalities and binocular contrast sensitivity and optotype acuity deficits in amblyopia. METHODS: We recruited 10 controls and 25 amblyopic subjects [Anisometropic = 6, Strabismic = 10, Mixed = 9]. We measured binocular contrast sensitivity at spatial frequencies 1,2, 4, 8, 12 and 16 and binocular and monocular optotype acuity using a staircase procedure. We recorded FEMs using high-resolution video-oculography and classified subjects as having no nystagmus(None = 9) or nystagmus without FMN(n = 7) and with Fusion Maldevelopment Nystagmus (FMN)(n = 9). We computed the fixation instability, amplitude and velocity of the fast and slow FEMs. RESULTS: Amblyopic subjects with and without nystagmus had worse binocular contrast sensitivity at spatial frequencies 12 and 16 and binocular optotype acuity than controls. The abnormalities were most pronounced in amblyopic subjects with FMN. Fixation instability of the Fellow Eye and Amblyopic Eye and vergence instability, amplitude of fast FEMs and velocity of slow FEMs were increased with reduced binocular contrast sensitivity and reduced optotype acuity in amblyopic subjects. CONCLUSIONS: Fixation instability of Fellow Eye and Amblyopic Eye, optotype acuity and contrast sensitivity deficits are seen under binocular viewing in amblyopic subjects with and without nystagmus but are most pronounced in those with FMN. FEMs abnormalities correlate with both lower order (contrast sensitivity) and higher order (optotype acuity) visual function impairment in amblyopia.


Amblyopia , Ocular Motility Disorders , Humans , Contrast Sensitivity , Eye Movements , Visual Acuity , Ocular Motility Disorders/etiology
7.
J Neurol Sci ; 442: 120438, 2022 11 15.
Article En | MEDLINE | ID: mdl-36242809

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.


Amblyopia , Dyslexia , Nystagmus, Pathologic , Ocular Motility Disorders , Humans , Amblyopia/complications , Dyslexia/complications , Eye Movements , Saccades
8.
J Neurol Sci ; 441: 120373, 2022 10 15.
Article En | MEDLINE | ID: mdl-36007287

Amblyopia is a neurodevelopmental disorder caused by abnormal visual experience in early life that affects 3-5% of the population. Amblyopia results in a host of monocular and binocular visual afferent function deficits including reduced visual acuity, contrast sensitivity, depth perception, interocular suppression, and efferent function abnormalities such as unstable and inaccurate fixation. Conventional treatments such as patching therapy and newer dichoptic treatments are not always successful as 30-40% of patients experience recurrence/regression of amblyopia. There are numerous review articles focused on visual afferent function deficits and treatment modalities and outcomes in amblyopia. Recently, the advent of high spatial and temporal resolution eye trackers has spurred studies on fixation eye movements (FEMs) in healthy controls and neurologic and ophthalmic disorders. In this focused review, we will summarize studies evaluating FEM abnormalities in amblyopia. We will first describe the common devices and techniques used to quantify fixation abnormalities, and then highlight the importance of systematically evaluating the eye movements under different viewing conditions and describe the parameters crucial in assessing FEM abnormalities in amblyopia. We will summarize the evidence suggesting that FEM abnormalities are not limited to the amblyopic eye only but also affects the fellow eye and that FEM abnormalities can serve as biomarkers to predict the impact of amblyopia on visual functions. Beyond diagnosis, we will discuss the treatment and prognostic implications of the evaluation of FEM abnormalities in clinical practice.


Amblyopia , Amblyopia/diagnosis , Amblyopia/therapy , Biomarkers , Eye Movements , Humans , Vision, Binocular , Visual Acuity
9.
J Neurol Sci ; 440: 120299, 2022 09 15.
Article En | MEDLINE | ID: mdl-35810513

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.


Eye Movements , Parkinson Disease , Eye , Fixation, Ocular , Humans , Saccades
10.
Am J Ophthalmol ; 240: 342-351, 2022 08.
Article En | MEDLINE | ID: mdl-35381203

PURPOSE: To determine whether rates of strabismus and associated visuomotor deficits differed among children with different severities of periventricular leukomalacia (PVL). DESIGN: Retrospective, case-control study. METHODS: Brain magnetic resonance images (MRI) obtained from 98 children aged ≥2 years were analyzed using a standardized scoring system: 67 of 98 had PVL (mean GA 31 weeks) and 31 of 98 did not have PVL (mean GA 29 weeks). Severity of PVL was scored as degree of damage to the posterior optic radiations and the splenium of the corpus callosum on MRI. Ophthalmologic examination data were collated to assess the prevalence of visuomotor deficits and the relationship to PVL severity (grades 1-3, mild to severe). RESULTS: Infantile strabismus was documented in 61% of children with mild, 74% with moderate, and 88% with severe PVL (esotropia: exotropia ratio 3.5:1). Associated ocular motor deficits also increased systematically with PVL severity: latent ("fusion maldevelopment") nystagmus (20%, 47%, and 40%, respectively), dissociated vertical deviation (13%, 28%, and 30%), and nasotemporal pursuit/optokinetic nystagmus asymmetry (23%, 38%, and 54%). Additionally, the prevalence of retrograde optic neuropathy increased with PVL severity (5%, 26%, and 38%). The prevalence of each of these signs was substantially lower in children who had no PVL. CONCLUSIONS: Children who suffer PVL are likely to develop the deficits of the infantile strabismus complex. The deficits tend to increase systematically as a function of PVL severity. These findings provide evidence that infantile strabismus is linked to perinatal damage to cerebral vergence and gaze pathways.


Leukomalacia, Periventricular , Nystagmus, Pathologic , Strabismus , Case-Control Studies , Child , Humans , Infant, Newborn , Leukomalacia, Periventricular/complications , Leukomalacia, Periventricular/diagnosis , Leukomalacia, Periventricular/epidemiology , Magnetic Resonance Imaging , Prevalence , Retrospective Studies , Strabismus/diagnosis , Strabismus/epidemiology
11.
Invest Ophthalmol Vis Sci ; 63(2): 33, 2022 02 01.
Article En | MEDLINE | ID: mdl-35212720

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.


Amblyopia/physiopathology , Eye Movements/physiology , Fixation, Ocular/physiology , Nystagmus, Pathologic/physiopathology , Vision, Binocular/physiology , Adolescent , Adult , Child , Child, Preschool , Female , Humans , Male , Middle Aged , Video Recording , Visual Acuity
12.
Cerebellum ; 21(1): 55-63, 2022 Feb.
Article En | MEDLINE | ID: mdl-33977497

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).


Immune System Diseases , Nystagmus, Pathologic , Ocular Motility Disorders , Glutamate Decarboxylase , Humans , Immune System Diseases/complications , Saccades
14.
J Neuroophthalmol ; 42(1): 45-55, 2022 03 01.
Article En | MEDLINE | ID: mdl-34812763

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.


Parkinson Disease , Saccades , Basal Ganglia , Eye Movements , Fixation, Ocular , Humans , Visual Perception/physiology
15.
J Neuroophthalmol ; 41(4): 442-451, 2021 12 01.
Article En | MEDLINE | ID: mdl-34788236

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.


Eye Movements , Parkinson Disease , Humans , Saccades
16.
J Neural Eng ; 18(4)2021 07 19.
Article En | MEDLINE | ID: mdl-34233315

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.


Parkinson Disease , Computer Simulation , Eye Movements , Humans , Neurons , Parkinson Disease/diagnosis , Saccades
17.
Sci Rep ; 11(1): 14417, 2021 07 13.
Article En | MEDLINE | ID: mdl-34257361

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.


Eye Movements , Saccades , Strabismus
18.
Eye Brain ; 13: 99-109, 2021.
Article En | MEDLINE | ID: mdl-33953627

PURPOSE: 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.

19.
J Comput Neurosci ; 49(3): 345-356, 2021 08.
Article En | MEDLINE | ID: mdl-33464428

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.


Deep Brain Stimulation , Parkinson Disease , Subthalamic Nucleus , Eye Movements , Humans , Models, Neurological , Parkinson Disease/therapy , Saccades
20.
Sci Rep ; 11(1): 1217, 2021 01 13.
Article En | MEDLINE | ID: mdl-33441575

Residual amblyopia is seen in 40% of amblyopic patients treated with part-time patching. Amblyopic patients with infantile onset strabismus or anisometropia can develop fusion maldevelopment nystagmus syndrome (FMNS). The purpose of this study was to understand the effects of presence of FMNS and clinical subtype of amblyopia on visual acuity and stereo-acuity improvement in children treated with part-time patching. Forty amblyopic children who had fixation eye movement recordings and at least 12 months of follow-up after initiating part-time patching were included. We classified amblyopic subjects per the fixational eye movements characteristics into those without any nystagmus, those with FMNS and patients with nystagmus without any structural anomalies that do not meet the criteria of FMNS or idiopathic infantile nystagmus. We also classified the patients per the clinical type of amblyopia. Patching was continued until amblyopia was resolved or no visual acuity improvement was noted at two consecutive visits. Children with anisometropic amblyopia and without FMNS have a faster improvement and plateaued sooner. Regression was only seen in patients with strabismic/mixed amblyopia particularly those with FMNS. Patients with FMNS had improvement in visual acuity but poor stereopsis with part-time patching and required longer duration of treatment.


Depth Perception/physiology , Eye Movements/physiology , Ocular Motility Disorders/therapy , Visual Acuity/physiology , Amblyopia/therapy , Anisometropia/therapy , Child , Child, Preschool , Female , Humans , Male , Nystagmus, Pathologic/therapy , Strabismus/therapy , Time Factors , Treatment Outcome
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