Review Article

Myasthenia gravis

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Abstract: Myasthenia gravis (MG) is an autoimmune antibody-mediated disorder which causes fluctuating weakness in ocular, bulbar and limb skeletal muscles. There are two major clinical types of MG. Ocular MG (OMG) affects extra ocular muscles associated with eye movement and eyelid function and generalized MG results in muscle weakness throughout the body. Patients with OMG have painless fluctuating extra ocular muscles weakness, diplopia and ptosis accompanied by normal visual acuity and pupillary function. Frequently, patients with OMG develop generalized MG over 24 months. Pure OMG is more often earlier in onset (<45 years) than generalized MG. It can also occur as part of an immune-genetic disorder or paraneoplastic syndrome related to thymus tumors. Diagnosis is based on clinical manifestations, laboratory findings, electrophysiological evaluation and pharmacologic tests. Therapeutic strategies for MG consist of symptom relieving medications (e.g., acetylcholine esterase inhibitors), immunosuppressive agents, and surgical intervention (e.g., thymectomy).

Review Article
Original Article

Objective electrophysiological contrast sensitivity with monofocal and multifocal intraocular lenses: a prospective clinical study

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Background: To compare objective electrophysiological contrast sensitivity function (CSF) in patients implanted with either multifocal intraocular lenses (MIOLs) or monofocal intraocular lenses (IOLs) by pattern reversal visual evoked potentials (prVEP) measurements.

Methods: Fourty-five cataract patients were randomly allocated to receive bilaterally: apodized diffractive-refractive Alcon Acrysof MIOL (A), full diffractive AMO Tecnis MIOL (B) or monofocal Alcon Acrysof IOL (C). Primary outcomes: 1-year differences in objective binocular CSF measured by prVEP with sinusoid grating stimuli of 6 decreasing contrast levels at 6 spatial frequencies. Secondary outcomes: psychophysical CSF measured with VCTS-6500, photopic uncorrected distance (UDVA), and mesopic and photopic uncorrected near and intermediate visual acuities (UNVA and UIVA respectively).

Results: Electrophysiological CSF curve had an inverted U-shaped morphology in all groups, with a biphasic pattern in Group B. Group A showed a lower CSF than group B at 4 and 8 cpd, and a lower value than group C at 8 cpd. Psychophysical CSF in group A exhibited a lower value at 12 cpd than group B. Mean photopic and mesopic UNVA and UIVA were worse in monofocal group compared to the multifocal groups. Mesopic UNVA and UIVA were better in group B.

Conclusions: Electrophysiological CSF behaves differently depending on the types of multifocal or monofocal IOLs. This may be related to the visual acuity under certain conditions or to IOL characteristics. This objective method might be a potential new tool to investigate on MIOL differences and on subjective device-related quality of vision.

Visual Impairment and Rehabilitation

AB102. Image blur perception in amblyopia: beyond edges

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Background: Understanding the neurophysiological mechanisms of Amblyopia, a neurodevelopmental disorder of the visual cortex, will bring us closer to full recovery. Past findings have been contradictory. Results have shown that despite having severe acuity impairment, amblyopes can nonetheless perceive sharp edges. In this study, we explore the representation of blur through a series of image blur-discrimination and matching tasks, to understand more about the amblyopes’ visual system.

Methods: Monocular image blur-discrimination thresholds were measured in a spatial two-alternative forced-choice procedure whereby subjects had to decide which image was the blurriest. Subjects also had to interocularly match pictures that were identical to those used for the image blur discrimination task. Ten amblyopes, as well as a group of ten controls were under study.

Results: Data on amblyopes and controls will be presented for both experiments. According to previous research that was done on blur-edge discrimination and matching, we predict that subjects’ performance will follow a dipper function, that is, all observers will be better at discriminating between both images when a small amount of blur is applied rather than when the image is either sharp or very blurry. We also predict that amblyopes’ blur discrimination will be noisier, but that they will paradoxically be able to match the sharpness of the images presented in the matching task.

Conclusions: This would confirm our hypothesis about amblyopes’ visual system, that they can represent blur levels defined by spatial frequencies that are beyond their resolution limit, and would also raise interesting questions about the visual system in general regarding the different perceptions driven by images versus edges.

Visual Impairment and Rehabilitation

AB096. Neurophysiological measures of stigma stereotypes

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Background: The perceptions surrounding assistive technology have been shown to be increasingly stigmatizing in older adult populations. This stigmatization can lead individuals to the abandonment of the assistive device. Until now, the methods of identifying or predicting the stigma surrounding assistive technology has mostly been qualitative in nature. Here we present a novel quantitate and qualitative research study that uses neuro-cognitive (psychophysics and EEG) and eye tracking technology, in addition to a new questionnaire to investigate the stigma associated with assistive devices. Therefore, this approach plays a major role in understanding and predicting the neural and physiological correlates associated to stigma.

Methods: Thirty-four older adults (>50 years) took part in the study. To determine the psychophysiological predictors of stigma surrounding assistive technologies, we monitored brain activity using EEG, heart rate and eye movements using an eye-tracker while participants viewed a series of images containing either an older or younger individual in different social scenarios (e.g., talking to doctor, at coffee shop). In each scenario, the individual uses either no assistive device, a low stigmatizing device (e.g., iPad), or a high stigmatizing device (e.g., electronic magnifier).

Results: Here we present preliminary analysis of the eye movement data. Analysis shows that in comparison to images that contained a low stigmatizing device, in images that contain high stigmatizing devices, the latency to fixate the device is shorter, first fixation duration is longer, and the total number of fixations on the device are higher. The environment that the devices is used in has no effect on eye movement metrics.

Conclusions: Although the sample size is small, and based on a healthy older-adult population, these initial observations would indicate that latency to fixate and first fixation duration are predictors of stigma associated with assistive devices. Future research should expand this prediction to those actively using assistive devices, and how the measures predict abandonment over time.

Cornea and Anterior segment

AB083. Intraocular lens biocompatibility: a novel, objective approach

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Background: Understanding factors that contribute to posterior capsular opacification (PCO) development is a significant public concern as treatment can lead to complications. In order to prevent PCO, a better understanding of intraocular lens (IOL) characteristics, including design and material, and patient interaction is required. Herein, we performed a retrospective multivariable analysis to determine which factors (IOL and patient based) were least likely to result in PCO.

Methods: One hundred eighty post-mortem eyes with implanted IOLs were collected from the Minnesota Eye Bank, along with clinical history, including date of cataract surgery and IOL model number. The capsular bag (CB) with the IOL implant was removed from all eyes to obtain digital images. PCO outcome was quantified on CB images using an objective, automated custom image analyzer (Medical Parachute Automated Detector Opacification Software). The software measured intensity and area of the opacification within the IOL optic edge, intra-optic edge (IOE = intensity/area), and in Soemmering’s ring (SR = intensity/area). Epidemiologic analysis assessed which IOL characteristics and patient-related factors correlated with PCO. IOL factors included material, edge design, lens filter, company, IOL model, decentration and time from cataract surgery to death. Patient factors included sex, age and diabetes, among others.

Results: Multivariate analyses showed non-diabetic patients had less PCO (P=0.05). Individuals 50–80 years old compared to 80+ had lower SR PCO (P=0.04). Non-blue light filter IOLs had lower SR and IOE PCO compared to filter IOLs (P=0.03, 0.001). Square and frosted optic edge design had lower SR and IOE PCO rates compared to OptiEdge and round optic edge design (P=0.002, 0.02). The IOL model that had the least PCO was the ZA9003 model, but this was only significant for SR and not IOE PCO (P=0.04). Adjusting for patient-factors, IOL lens model was no longer a confounding factor for PCO. Patients with an IOL implanted for <7 years had lower SR PCO, whereas lower IOE PCO was only seen in implants <4 years old (P=0.0001, 0.04).

Conclusions: In order to generate a lens that does not develop PCO, it is critical to understand the IOL- and patient-related factors that lead to PCO development. Based on our data, the most susceptible patients are elderly and diabetic, and it may be preferable to implant a square and frosted edge lens without blue-light filtering in this cohort.

Brain and Perception

AB073. Correlations between control of saccadic eye movements and performance in other cognitive tasks in younger adults, older adults and patients with Parkinson’s disease

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Background: Cognitive control is defined as the ability to act flexibly in the environment by either behaving automatically or inhibiting said automatic behaviour and it can be measured using an interleaved pro/anti-saccade task. Decline in cognitive control has been attributed to normal aging and neurological illnesses such as Parkinson’s disease (PD) as well as decline in other cognitive abilities. This parallel might highlight the role played by cognitive control in information processing and working memory. However, little is known about the relationship between cognitive control and other cognitive processes such as visual memory, decision making, and visual search. We thus propose to correlate the incidence of impaired cognitive control with deficits in visual memory, decision making and visual search in three groups: younger adults, older adults and patients with idiopathic PD.

Methods: Seventy-one participants, namely 34 adults (M =22.75, SD =3.8), 22 older adults (M =67.4, SD =8.3), and 20 PD patients (M =65.59, SD =8.2) performed four tasks: interleaved pro/anti-saccade, visual memory, decision making, and serial and pop-out visual search.

Results: Results show that within each group, anti-saccade error rate (ER) were significantly and negatively correlated with visual memory ER (ryounger =?0.378, P=0.036; rolder =?0.440, Polder =0.046; rPD =?0.609, P=0.016). On the other hand, correct decision-making reaction times (RT) were significantly correlated with anti-saccade ER, and RTs only in older adults (rER =0.529, P=0.014; rRT =0.512, P=0.018) and PD patients (rER =0.727, P=0.012; rRT =0.769, P=0.001). For visual search, PD patients showed a significant relationship between RTs for correct pro-saccades and pop-out (r=0.665, P=0.007), and serial (r=0.641, P=0.010) search RTs. Furthermore, there was a significant correlation between MoCA scores and anti-saccade RTs (r=?0.559, P=0.030) and ER (r=?0.562, P=0.029) in PD patients. Taken together, these results support the hypothesis of PD patients’ reliance on bottom-up processes as top-down processes decline. For younger adults, there was a significant correlation between serial search performance and both anti-saccade ER (r=0.488, P=0.005), and correct pro-saccade ER (r=0.413, P=0.021). In older adults, this relationship was absent, but anti-saccade ER significantly correlated with pop-out search times (r=0.473, P=0.030).

Conclusions: We found significant relationships between cognitive tasks and cognitive control as measured through the interleaved pro/anti-saccade task across and within participant groups, providing evidence of the appropriateness of the use of the interleaved pro/anti-saccade task as a measure of overall cognitive control.

Brain and Perception

AB063. Contrasting effects of exogenous attention on saccades and reaches

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Background: The goal of the present study was to determine whether exogenous attentional mechanisms involved in motor planning for saccades and reaches are the same for both effectors or are independent for each effector. We compared how eye and arm movement parameters, notably reaction time and amplitude, are affected by modulating exogenous attentional visual cues at different locations relative to a target.

Methods: Thirteen participants (M =22.8, SD =1.5) were asked to perform a task involving exogenous attentional allocation and movement planning. The participants were asked to fixate and maintain their hand at an initial position on a screen in front of them (left or right of screen centre) and then, at the disappearance of the fixation cross, perform an eye or arm movement, or both, to a target square (mirror location of fixation cross). A distractor appeared momentarily just before the appearance of the target at one of seven equidistant locations on the horizontal meridian. Saccade reaction times (SRTs), reach reaction times (RRTs) and amplitudes were calculated.

Results: Compared to the neutral condition (where no distractor was presented), distractors overall did not result in a facilitation of SRTs at any location (shorter SRTs), rather only a strong inhibition (longer SRTs) as a function of distractor target distance. In contrast, RRTs showed strong facilitation at the target location and less inhibition at further distances. However, both SRTs and RRTs followed a similar pattern in that RTs were shortest closer to the target position and were increasingly longer as a function of distractor target distance. In terms of amplitude, there was no effect of the distractor on reach endpoints, whereas, for saccades, there was an averaging effect of distractor position on saccade endpoints, but only for saccades with short SRTs. These effects were similar when either effector movement was performed alone or together.

Conclusions: These findings suggest that attentional selection mechanisms have both similar and differential effects on motor planning depending on the effectors used, providing evidence for both effector independent and effector dependent attentional selection mechanisms. This study furthers understanding of the operating mechanisms of exogenous attention on eye and arm movements and the interaction between sensory and motor systems.

Brain and Perception

AB062. Cortical state contribution to neuronal response variability

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Background: Visual cortex neurons often respond to stimuli very differently on repeated trials. This trial-by-trial variability is known to be correlated among nearby neurons. Our long-term goal is to quantitatively estimate neuronal response variability, using multi-channel local field potential (LFP) data from single trials.

Methods: Acute experiments were performed with anesthetized (Remifentanil, Propofol, nitrous oxide) and paralyzed (Gallamine Triethiodide) cats. Computer-controlled visual stimuli were displayed on a gamma-corrected CRT monitor. For the principal experiment, two kinds of visual stimuli were used: drifting sine-wave gratings, and a uniform mean-luminance gray screen. These two stimuli were each delivered monocularly for 100 sec in a random order, for 10 trials. Multi-unit activity (MUA) and LFP signals were extracted from broadband raw data acquired from Area 17 and 18 using A1X32 linear arrays (NeuroNexus) and the OpenEphys recording system. LFP signal processing was performed using Chronux, an open-source MATLAB toolbox. Current source density (CSD) analysis was performed on responses to briefly flashed full-field stimuli using the MATLAB toolbox, CSDplotter. The common response variability (global noise) of MUA was estimated using the model proposed by Scholvinck et al. [2015].

Results: On different trials, a given neuron responded with different firing to the same visual stimuli. Within one trial, a neuron’s firing rate also fluctuated across successive cycles of a drifting grating. When the animal was given extra anesthesia, neurons fired in a desynchronized pattern; with lighter levels of anesthesia, neuronal firing because more synchronized. By examining the cross-correlations of LFP signals recorded from different cortical layers, we found LFP signals could be divided to two groups: those recorded in layer IV and above, and those from layers V and VI. Within each group, LFP signals recorded by different channels are highly correlated. These two groups were observed in lighter and deeper anesthetized animals, also in sine-wave and uniform gray stimulus conditions. We also investigated correlations between LFP signals and global noise. Power in the LFP beta band was highly correlated with global noise, when animals were in deeper anesthesia.

Conclusions: Brain states contribute to variations in neuronal responses. Raw LFP correlation results suggest that we should analyze LFP data according to their laminar organization. Correlation of low-frequency LFP under deeper anesthesia with global noise gives us some insight to predict noise from single-trial data, and we hope to extend this analysis to lighter anesthesia in the future.

Brain and Perception

AB053. Oscillatory activity specific to peripheral emotional treatment induced by a visual steady state

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Background: Research suggests that the analysis of facial expressions by a healthy brain would take place approximately 170 ms after the presentation of a facial expression in the superior temporal sulcus and the fusiform gyrus, mostly in the right hemisphere. Some researchers argue that a fast pathway through the amygdala would allow automatic and early emotional treatment around 90 ms after stimulation. This treatment would be done subconsciously, even before this stimulus is perceived and could be approximated by presenting the stimuli quickly on the periphery of the fovea. The present study aimed to identify the neural correlates of a peripheral and simultaneous presentation of emotional expressions through a frequency tagging paradigm.

Methods: The presentation of emotional facial expressions at a specific frequency induces in the visual cortex a stable and precise response to the presentation frequency [i.e., a steady-state visual evoked potential (ssVEP)] that can be used as a frequency tag (i.e., a frequency-tag to follow the cortical treatment of this stimulus. Here, the use of different specific stimulation frequencies allowed us to label the different facial expressions presented simultaneously and to obtain a reliable cortical response being associated with (I) each of the emotions and (II) the different times of presentations repeated (1/0.170 ms =~5.8 Hz, 1/0.090 ms =~10.8 Hz). To identify the regions involved in emotional discrimination, we subtracted the brain activity induced by the rapid presentation of six emotional expressions of the activity induced by the presentation of the same emotion (reduced by neural adaptation). The results were compared to the hemisphere in which attention was sought, emotion and frequency of stimulation.

Results: The signal-to-noise ratio of the cerebral oscillations referring to the treatment of the expression of fear was stronger in the regions specific to the emotional treatment when they were presented in the subjects peripheral vision, unbeknownst to them. In addition, the peripheral emotional treatment of fear at 10.8 Hz was associated with greater activation within the Gamma 1 and 2 frequency bands in the expected regions (frontotemporal and T6), as well as desynchronization in the Alpha frequency bands for the temporal regions. This modulation of the spectral power is independent of the attentional request.

Conclusions: These results suggest that the emotional stimulation of fear presented in the peripheral vision and outside the attentional framework elicit an increase in brain activity, especially in the temporal lobe. The localization of this activity as well as the optimal stimulation frequency found for this facial expression suggests that it is treated by the fast pathway of the magnocellular layers.

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