Fixational microsaccades: A quantitative and objective measure of disability in multiple sclerosis.

BACKGROUND: Objective tools for prognosis and disease progression monitoring in multiple sclerosis (MS) are lacking. The visuomotor system could be used to track motor dysfunction at the micron scale through the monitoring of fixational microsaccades. AIMS: The aim of this study was to evaluate whether microsaccades are correlated with standard MS disability metrics and to assess whether these methods play a predictive role in MS disability. METHOD: We used a custom-built retinal eye tracker, the tracking scanning laser ophthalmoscope (TSLO), to record fixation in 111 participants with MS and 100 unaffected controls. RESULTS: In MS participants, a greater number of microsaccades showed significant association with higher Expanded Disability Status Scale score (EDSS, p < 0.001), nine-hole peg test (non-dominant: p = 0.006), Symbol Digit Modalities Test (SMDT, p = 0.014), and Functional Systems Scores (FSS) including brainstem (p = 0.005), cerebellar (p = 0.011), and pyramidal (p = 0.009). Both brainstem FSS and patient-reported fatigue showed significant associations with microsaccade number, amplitude, and peak acceleration. Participants with MS showed a statistically different average number (p = 0.020), peak vertical acceleration (p = 0.003), and vertical amplitude (p < 0.001) versus controls. Logistic regression models for MS disability were created using TSLO microsaccade metrics and paraclinical tests with ⩾80% accuracy. CONCLUSION: Microsaccades provide objective measurements of MS disability level and disease worsening.

Impact of simulated micro-scotomas on reading performance in central and peripheral retina.

Observers with central field loss typically fixate within a non-foveal region called the preferred retinal locus, which can include localized sensitivity losses, or micro-scotomas (Krishnan and Bedell, 2018). In this study, we simulated micro-scotomas at the fovea and in the peripheral retina to assess their impact on reading speed. Ten younger (<36 years old) and 8 older (>50 years old) naïve observers with normal vision monocularly read high and/or low contrast sentences, presented at or above the critical print size for young observers at the fovea and at 5 and 10 deg in the inferior visual field. Reading material comprised MNREAD sentences and sentences taken from novels that were presented in rapid serial visual presentation (RSVP) format. Randomly distributed 13 × 13 arc min blocks corresponding to 0-78% of the text area (corresponding to ∼0-17 micro-scotomas/deg2) were set to the background luminance to simulate micro-scotomas. A staircase algorithm estimated maximum reading speed from the threshold exposure duration for each combination of retinal eccentricity, contrast and micro-scotoma density in both age groups. Log10(RSVP reading speed) decreased significantly with simulated micro-scotoma density and eccentricity. Across conditions, reading speed was slower with low-compared to high-contrast text and was faster in younger than older normal observers. For a given eccentricity and contrast, a higher density of random element losses maximally affected older observers with normal vision. These outcomes may explain some of the reading deficits observed in older observers with central field loss.

Blur Detection, Depth of Field, and Accommodation in Emmetropic and Hyperopic Children.

SIGNIFICANCE: Our results demonstrate that blur detection thresholds are elevated in young children compared with adults, and poorer blur detection thresholds are significantly correlated with the magnitude of accommodative microfluctuations. Given that accommodative microfluctuations are greater with greater accommodative responses, these findings may have implications for young uncorrected hyperopes. PURPOSE: This study investigated the association between subjective blur detection thresholds and accommodative microfluctuations in children 3 years to younger than 10 years old and adults. METHODS: Blur detection thresholds were determined in 49 children with habitually uncorrected refractive error (+0.06 to +4.91 diopters [D] spherical equivalent) and 10 habitually uncorrected adults (+0.08 to +1.51 D spherical equivalent) using a custom blur chart with 1° sized optotypes at 33 cm. Letters were blurred by convolution using a Gaussian kernel (SDs of 0.71 to 11.31 arc minutes in √2 steps). Subjective depth of field was determined in subjects 6 years or older and adults. Accommodative microfluctuations, pupils, and lag were measured using infrared photorefraction (25 Hz). RESULTS: Children had greater blur detection thresholds (P < .001), accommodative microfluctuations (P = .001), and depth of field (P < .001) than adults. In children, increased blur detection thresholds were associated with increased accommodative microfluctuations (P < .001), increased uncorrected hyperopia (P = .01), decreased age (P < .001), and decreased pupil size (P = .01). In a multiple linear regression analysis, blur detection thresholds were associated with accommodative microfluctuations (P < .001) and age (P < .001). Increased accommodative microfluctuations were associated with increased uncorrected hyperopia (P = .004) and decreased pupil size (P = .003) and independently associated with uncorrected hyperopia (P = .001) and pupil size (P = .003) when controlling for age and lag. CONCLUSIONS: Children did not have adult-like blur detection thresholds or depth of field. Increased accommodative microfluctuations and decreased age were independently associated with greater blur detection thresholds in children 3 years to younger than 10 years. Larger amounts of uncorrected hyperopia in children appear to increase blur detection thresholds because the greater accommodative demand and resulting response increase accommodative microfluctuations.

Scotoma Visibility and Reading Rate with Bilateral Central Scotomas.

PURPOSE: In this experiment, we tested whether perceptually delineating the scotoma location and border with a gaze contingent polygon overlay improves reading speed and reading eye movements in patients with bilateral central scotomas. METHODS: Eight patients with age-related macular degeneration and bilateral central scotomas read aloud MNRead style sentences with their preferred eye. Eye movement signals from an EyeLink II eyetracker were used to create a gaze contingent display in which a polygon overlay delineating the area of the patient's scotoma was superimposed on the text during 18 of the 42 trials. Blocks of six trials with the superimposed polygon were alternated with blocks of six trials without the polygon. Reading speed and reading eye movements were assessed before and after the subjects practiced reading with the polygon overlay. RESULTS: All of the subjects but one showed an increase in reading speed. A paired-samples t-test for the group as a whole revealed a statistically significant increase in reading speed of 0.075 ± 0.060 (SD) log wpm after reading with the superimposed polygon. Individual subjects demonstrated significant changes in reading eye movements, with the greatest number of subjects demonstrating a shift in the average vertical fixation locus. Across subjects, there was no significant difference between the initial and final reading eye movements in terms of saccades per second, average fixation duration, average amplitude of saccades, or proportion of non-horizontal saccades. CONCLUSIONS: The improvement in reading speed (0.075 log wpm or 19%) over the short experimental session for the majority of subjects indicates that making the scotoma location more visible is potentially beneficial for improving reading speed in patients with bilateral central scotomas. Additional research to examine the efficacy of more extended training with this paradigm is warranted.

Progress on Developing Adaptive Optics-Optical Coherence Tomography for In Vivo Retinal Imaging: Monitoring and Correction of Eye Motion Artifacts.

Recent progress in retinal image acquisition techniques, including optical coherence tomography (OCT) and scanning laser ophthalmoscopy (SLO), combined with improved performance of adaptive optics (AO) instrumentation, has resulted in improvement in the quality of in vivo images of cellular structures in the human retina. Here, we present a short review of progress on developing AO-OCT instruments. Despite significant progress in imaging speed and resolution, eye movements present during acquisition of a retinal image with OCT introduce motion artifacts into the image, complicating analysis and registration. This effect is especially pronounced in high-resolution datasets acquired with AO-OCT instruments. Several retinal tracking systems have been introduced to correct retinal motion during data acquisition. We present a method for correcting motion artifacts in AO-OCT volume data after acquisition using simultaneously captured adaptive optics-scanning laser ophthalmoscope (AO-SLO) images. We extract transverse eye motion data from the AO-SLO images, assign a motion adjustment vector to each AO-OCT A-scan, and re-sample from the scattered data back onto a regular grid. The corrected volume data improve the accuracy of quantitative analyses of microscopic structures.

How the unstable eye sees a stable and moving world.

Eye motion, even during fixation, results in constant motion of the image of the world on our retinas. Vision scientists have long sought to understand the process by which we perceive the stable parts of the world as unmoving despite this instability and perceive the moving parts with realistic motion. We used an instrument capable of delivering visual stimuli with controlled motion relative to the retina at cone-level precision while capturing the subjects' percepts of stimulus motion with a matching task. We found that the percept of stimulus motion is more complex than conventionally thought. Retinal stimuli that move in a direction that is consistent with eye motion (i.e., opposite eye motion) appear stable even if the magnitude of that motion is amplified. The apparent stabilization diminishes for stimulus motions increasingly inconsistent with eye motion direction. Remarkably, we found that this perceived direction-contingent stabilization occurs separately for each separately moving pattern on the retina rather than for the image as a whole. One consequence is that multiple patterns that move at different rates relative to each other in the visual input are perceived as immobile with respect to each other, thereby disrupting our hyperacute sensitivity to target motion against a frame of reference. This illusion of relative stability has profound implications regarding the underlying visual mechanisms. Functionally, the system compensates retinal slip induced by eye motion without requiring an extremely precise optomotor signal and, at the same time, retains an exquisite sensitivity to an object's true motion in the world.

Spatial-temporal contrast sensitivity of the eye alignment reflex.

The binocular alignment of the eyes involves both voluntary and reflexive mechanisms, but little is known about the visual input and neurological pathway of the reflex component. Our studies examined the role of spatiotemporal frequency and contrast in the control of reflex eye alignment, and compared the contrast sensitivity of the alignment reflex with psychophysical contrast sensitivity. We measured the contrast sensitivity of vertical disparity-driven vergence eye movements in response to bandwidth filtered static or 6 Hz counterphase flickering noise and measured psychophysical detection sensitivity for the same stimuli. Contrast thresholds for producing a detectable vertical alignment change (measured with nonius lines) were determined using a staircase method for 7 spatial frequencies [0.25-16 cycles per degree] and 3 vertical disparities [5, 10, and 30 arcmin] in 7 adults with normal or corrected to normal vision. The main findings of this study are, (1) the vertical alignment reflex had overall relatively high contrast sensitivity, comparable to but somewhat less than visual detection thresholds, (2) the most effective stimulus spatial frequency scaled in inverse proportion to the disparity being stimulated, and (3) unlike psychophysical contrast sensitivity, the eye alignment reflex contrast sensitivity was not improved by flickering low spatial frequencies.

Unreferenced spatial localization under monocular and dichoptic viewing conditions.

Knowledge of eye position in the brain is critical for localization of objects in space. To investigate the accuracy and precision of eye position feedback in an unreferenced environment, subjects with normal ocular alignment attempted to localize briefly presented targets during monocular and dichoptic viewing. In the task, subjects' used a computer mouse to position a response disk at the remembered location of the target. Under dichoptic viewing (with red (right eye)-green (left eye) glasses), target and response disks were presented to the same or alternate eyes, leading to four conditions [green target-green response cue (LL), green-red (LR), red-green (RL), and red-red (RR)]. Time interval between target and response disks was varied and localization errors were the difference between the estimated and real positions of the target disk. Overall, the precision of spatial localization (variance across trials) became progressively worse with time. Under dichoptic viewing, localization errors were significantly greater for alternate-eye trials as compared to same-eye trials and were correlated to the average phoria of each subject. Our data suggests that during binocular dissociation, spatial localization may be achieved by combining a reliable versional efference copy signal with a proprioceptive signal that is unreliable perhaps because it is from the wrong eye or is too noisy.

Stimulus dependence of interocular suppression.

Interocular suppression is the phenomenon in which the signal from one eye inhibits the other eye in the presence of dissimilar images. Various clinical and laboratory-based tests have been used to assess suppression, which vary in color, contrast, and stimulus size. These stimulus variations may yield different spatial extents of suppression, which makes it difficult to compare the outcomes. To evaluate the role of stimulus characteristics, we measured the suppression zone using a binocular rivalry paradigm in normally-sighted observers by systematically varying the stimulus parameters. The stimuli consist of a constantly visible horizontal reference seen by one eye while two vertical suppressors were presented to the other eye. With a keypress, the suppressors appeared for 1 s, to induce a transient suppression zone in the middle part of the reference. Subjects adjusted the width between the suppressors to determine the zone. The zone decreased significantly with increasing spatial frequency and lower contrast. The width was 1.4 times larger than the height. The zone was smaller with negative compared to positive contrast polarity but independent of eye dominance, luminance, and colored filters. A departure from scale invariance was captured with a model suggesting a stimulus-dependent and a small fixed non-stimulus-dependent portion.

Saccadic lens instability increases with accommodative stimulus in presbyopes.

An SRI dual Purkinje image (dPi) eye tracker was used to measure lens wobble following saccades with increasing accommodative effort as an indirect measure of ciliary muscle function in presbyopes. Ten presbyopic subjects executed 32 four-degree saccades at 1-s intervals between targets arranged in a cross on illuminated cards at each of 9 viewing distances ranging from 0.5- to 8-D accommodative demands. Post-saccadic lens wobble artifacts were extracted by subtraction of P1 (H(1)/V(1)) position signals from P4 signals (Theta(H)/Theta(V)), both of which were sampled by the eye tracker at 100 Hz. A ray tracing eye model was also employed to model the fourth Purkinje image shifts for a range of lens translations and tilts. Combining all saccades from all subjects showed a significant positive relationship between lens wobble artifact amplitude and accommodative demand. Eye model simulations indicated that artifacts of the amplitude measured could arise from either lens tilts (in the range of 2-4 degrees) or lens translations (in the range of 0.1 to 0.2 mm). Saccadic lens wobble artifacts increase with accommodative effort in presbyopes, indicating preserved ciliary muscle function and greater relaxation of zonular tension with accommodative effort. Variation across subjects may reflect differences in accommodative effort, ciliary muscle function for a given effort, and/or in intraocular anatomy.

Signals of eye-muscle proprioception modulate perceived motion smear.

Achieving clear perception during eye movements is one of the major challenges that the human visual system has to face every day. Like most light sensitive mechanisms, the human visual system has a finite integration time that may cause moving images to appear smeared. By comparing the perceived motion smear during ongoing eye movements and fixation, previous studies indicated that smear is reduced by a neural compensation mechanism that uses "extra-retinal information" about eye movements. However, it is not clear whether eye-muscle proprioception (afferent input), internal copies of efferent oculomotor commands (efference copy), or both contribute to the smear reduction. The present study found that similar reductions of perceived motion smear occur during passive eye movement (which is signaled only by eye-muscle proprioception) and during active pursuit tracking (for which efference copy signals exist as well). These results reveal a novel neural contribution for maintaining visual clarity and stand in contrast to previous reports that eye-muscle proprioception makes only a minor contribution to visual perception.

Psychophysical measurements of referenced and unreferenced motion processing using high-resolution retinal imaging.

BACKGROUND: Motion detection thresholds with a stationary frame of reference are significantly lower than unreferenced motion thresholds. To account for this, previous studies have postulated the existence of compensatory mechanisms, driven by the presence of a surround, that cancel the effects of eye movements. In the present study we used an adaptive optics scanning laser ophthalmoscope (AOSLO) to investigate the effects of retinal jitter due to fixation eye movements on referenced and unreferenced motion thresholds. METHODS: The stimuli were produced by modulation of the AOSLO imaging beam, so that the absolute retinal position of targets was recorded. In Experiment 1 subjects made up/down motion judgments of a dark horizontal bar presented against a stationary 1-degree bright background. In Experiment 2 unreferenced motion thresholds were measured with isolated bright horizontal bars in otherwise complete darkness. In both experiments, AOSLO images for each trial were analyzed offline to extract retinal jitter and the retinal position of targets. RESULTS: For referenced motion, the results were consistent with complete compensation for eye movements by the visual system. In the unreferenced motion case eye movements adversely affected motion judgments, although there was evidence of partial compensation for such eye movements. CONCLUSIONS: Compensatory processes completely cancel the effect of fixation jitter for referenced motion but such compensation is partial for unreferenced motion.

The influence of endogenous attention on contrast perception, contrast discrimination, and saccadic reaction time.

Visual spatial attention has been shown to influence both contrast detection and suprathreshold contrast perception, as well as manual and saccadic reaction times (SRTs). Because SRTs are influenced also by stimulus contrast, we investigated if the enhancement of perceived contrast that accompanies attention could account for the shorter SRTs observed for attended targets locations. We conducted two dual-task experiments to assess psychophysical and oculomotor responses to non-foveal targets of various contrast for different spatial-attention-cueing conditions. Cues were either: valid, an arrow at fixation pointing in the direction of the upcoming target; invalid, an arrow pointing in a different direction from the target; or neutral, a small circle instead of an arrow. In both experiments, subjects were instructed to make a saccade to the location of a subsequent, briefly flashed target. In the first experiment, the psychophysical judgment was a two-alternative-forced-choice (2AFC) contrast-detection task, in which subjects reported whether the flashed target was at a near (3°) or far (6°) eccentricity. In the second experiment, the judgment was a contrast matching task, in which subjects reported whether the target's contrast was higher or lower than a remembered standard contrast. The results exhibit a robust, ∼40-50 ms reduction of SRTs with a valid compared to an invalid cue. Cueing effects on contrast detection and matching were small and inconsistent across subjects. Hence, the observed decrease in SRTs could not be accounted for fully by an enhancement in the target's effective contrast due to attention, as attended and unattended targets that were equally detectable or were perceived to have the same suprathreshold contrast showed substantial differences in SRT.

Stereoscopic depth perception from oblique phase disparities.

In order to understand the role of oblique retinal image disparities in the perception of stereoscopic depth, we measured the depth perceived from random dot stereograms in which phase disparities were introduced in a selected band of stimulus orientations. A band of orientation was defined by a center orientation that ranged from 7.5 (near vertical) to 82.5 o[rientation]deg and by a bandwidth that was defined as the difference between the highest and the lowest orientation in the band. The bandwidths tested were 15, 30 and 45 odeg. A constant phase disparity of 90 p[hase]deg was introduced in all of the oriented spatial frequency components within the orientation band and the perceived depth of each stimulus was matched using a small square binocular probe. For each bandwidth, perceived depth increased with an increase in the center orientation up to approximately 60 odeg. This suggests that the human stereovision system derives a large proportion of information about perceived stereoscopic depth from oblique phase disparities. Simulations using an energy model of stereoscopic depth perception indicate that oblique phase disparities are unlikely to be processed by neural mechanisms tuned to near-vertical orientations within the stimulus. Our results therefore suggest that oblique retinal disparities are initially detected as oblique phase disparities by binocular mechanisms tuned to oblique orientations. Because the perceived depth from oblique phase disparities is consistent with the trigonometrically determined equivalent horizontal disparities, we presume that the information from oblique phase disparities is included in the visual system's computation of the horizontal retinal disparity.

Eye movement testing in clinical examination.

The clinical vision examination routinely includes an evaluation of ocular motor function. In a number of diverse situations, thorough objective recording of eye movements is warranted, using any of a variety of eye-tracking technologies that are available currently to clinicians. Here we review the clinical uses of eye tracking, with both an historical and contemporary view. We also consider several new imaging technologies that are becoming available in clinics and include inbuilt eye-tracking capability. These highly sensitive eye trackers should be useful for evaluating a variety of subtle, but important, oculomotor signs and disorders.

D(max) for stereoscopic depth perception with simulated monovision correction.

PURPOSE: Persons who wear monovision correction typically receive a clear image in one eye and a blurred image in the other eye. Although monovision is known to elevate the minimum stereoscopic threshold (Dmin), it is uncertain how it influences the largest binocular disparity for which the direction of depth can reliably be perceived (Dmax). In this study, we compared Dmax for stereo when one eye's image is blurred to Dmax when both eyes' images are either clear or blurred. METHODS: The stimulus was a pair of vertically oriented, random-line patterns. To simulate monovision correction with +1.5 or +2.5 D defocus, the images of the line patterns presented to one eye were spatially low-pass filtered while the patterns presented to the other eye remained unfiltered. RESULTS: Compared to binocular viewing without blur, Dmin is elevated substantially more in the presence of monocular than binocular simulated blur. Dmax is reduced in the presence of simulated monocular blur by between 13 and 44%, compared to when the images in both eyes are clear. In contrast, when the targets presented to both eyes are blurred equally, Dmax either is unchanged or increases slightly, compared to the values measured with no blur. CONCLUSION: In conjunction with the elevation of Dmin, the reduction of Dmax with monocular blur indicates that the range of useful stereoscopic depth perception is likely to be compressed in patients who wear monovision corrections.

The influence of unilateral uncorrected astigmatism on binocular vision and fixation disparity.

PURPOSE: It is accepted practice to use a spherical equivalent power as an alternative contact lens correction for those patients with lower amounts of astigmatism, allowing for an easier fit, but the blur caused by one diopter of uncorrected astigmatism can reduce acuity of 6/6 to that of about 6/8. This is usually deemed acceptable monocularly, often retaining a good binocular acuity. The purpose of this study is to explore how monocular astigmatic blur may also affect the patient's binocular vision function. METHODS: A trial frame was outfitted with full correction for 20 healthy subjects (mean age 25.5 years, range 19-36 years) and a baseline horizontal fixation disparity was measured at a distance of 1 m. Thereafter, fixation disparity was measured with induced monocular astigmatic blur in the right eye, creating an astigmatic error in the amounts of -0.75 and -1.25 in axis 90 and axis 45. RESULTS: It was determined that the differences among full correction and the 4 different types of astigmatic blur were not significant when analyzed as one group (P = 0.5445), nor when separated into groups according to whether the subject had naturally occurring astigmatism or not, (astigmatic group, P = 0.3801; non-astigmatic group, P = 0.5899). CONCLUSIONS: Monocular astigmatic blur in the amounts of -0.75 and -1.25 did not have a significant effect on tested subjects with regard to the amount of blur or axis orientation. This low amount of blur is likely within the range of compensation for the subjects, proving that spherical equivalent contact lenses are a viable option for low amounts of astigmatic error.

Horizontal gaze nystagmus: a review of vision science and application issues.

The Horizontal Gaze Nystagmus (HGN) test is one component of the Standardized Field Sobriety Test battery. This article reviews the literature on smooth pursuit eye movement and gaze nystagmus with a focus on normative responses, the influence of alcohol on these behaviors, and stimulus conditions similar to those used in the HGN sobriety test. Factors such as age, stimulus and background conditions, medical conditions, prescription medications, and psychiatric disorder were found to affect the smooth pursuit phase of HGN. Much less literature is available for gaze nystagmus, but onset of nystagmus may occur in some sober subjects at 45 degrees or less. We conclude that HGN is limited by large variability in the underlying normative behavior, from methods and testing environments that are often poorly controlled, and from a lack of rigorous validation in laboratory settings.