The purpose of this pilot study was to investigate the light-induced pupillary and lacrimation responses mediated by intrinsically photosensitive retinal ganglion cells (ipRGCs) in migraine. Ten ...participants with episodic migraine and normal tear production, as well as eleven visually normal controls participated in this study. Following an initial baseline trial (no light flash), participants received seven incremental and alternating red and blue light flashes. Pupillometry recording of the left eye and a 1-min anesthetized Schirmer's test of the right eye (using 0.5% proparacaine) were performed simultaneously. Intrinsic and extrinsic ipRGC photoactivities did not differ between migraine participants and controls across all intensities and wavelengths. Migraine participants, however, had significantly lower lacrimation than controls following the highest blue intensity. A positive correlation was found between melanopsin-driven post-illumination pupillary responses and lacrimation following blue stimulation in both groups. Our results show that participants with self-reported photophobia have normal ipRGC-driven responses, suggesting that photophobia and pupillary function may be mediated by distinct ipRGC circuits. The positive correlation between melanopsin-driven pupillary responses and light-induced lacrimation suggests the afferent arm of the light-induced lacrimation reflex is melanopsin-mediated and functions normally in migraine. Lastly, the reduced melanopsin-mediated lacrimation at the highest stimulus suggests the efferent arm of the lacrimation reflex is attenuated under certain conditions, which may be a harbinger of dry eye in migraine.
New behavioral treatment methods, including dichoptic training, perceptual learning, and video gaming, have been proposed to improve visual function in adult amblyopia. Here, we conducted a ...meta-analysis of these methods to investigate the factors involved in amblyopia recovery and their clinical significance.
Mean and individual participant data meta-analyses were performed on 24 studies using the new behavioral methods in adults. Studies were identified using PubMed, Google Scholar, and published reviews.
The new methods yielded a mean improvement in visual acuity of 0.17 logMAR with 32% participants achieving gains ≥ 0.2 logMAR, and a mean improvement in stereo sensitivity of 0.01 arcsec-1 with 42% of participants improving ≥2 octaves. The most significant predictor of treatment outcome was visual acuity at the onset of treatment. Participants with more severe amblyopia improved more on visual acuity and less on stereo sensitivity than those with milder amblyopia. Better initial stereo sensitivity was a predictor of greater gains in stereo sensitivity following treatment. Treatment type, amblyopia type, age, and training duration did not have any significant influence on visual and stereo acuity outcomes.
Our analyses showed that some participants may benefit from the new treatments; however, clinical trials are required to confirm these findings. Despite the diverse nature of the new behavioral methods, the lack of significant differences in visual and stereo sensitivity outcomes among them suggests that visual attention-a common element among the varied treatment methods-may play an important role in amblyopia recovery.
Amblyopia is a neurodevelopmental visual disorder caused by abnormal visual experience in childhood. In addition to known visual deficits, there is evidence for changes in audiovisual integration in ...amblyopia using explicit tasks. We examined audiovisual integration in amblyopia using an implicit task that is more relevant in a real-world context.
A total of 11 participants with amblyopia and 16 controls were tested binocularly and monocularly on the sound-induced flash illusion, in which flashes and beeps are presented concurrently and the perceived number of flashes is influenced by the number of beeps. The task used 1 to 2 rapid peripheral flashes presented with 0 to 2 beeps, at 5 stimulus onset asynchronies, that is, beep (-200 milliseconds, -100 milliseconds) or flash leading (100 milliseconds, 200 milliseconds) or simultaneous (0 milliseconds). Participants reported the number of perceived flashes. Susceptibility was indicated by a "2 flashes" response to "fission" (1 flash, 2 beeps) or "1 flash" to "fusion" (2 flashes, 1 beep).
For fission with the beep leading during binocular viewing, controls showed an expected decrease in illusion strength as stimulus onset asynchronies increased, whereas the illusion strength remained constant in participants with amblyopia, indicating a wider temporal binding window in amblyopia (P = 0.007). For fusion, participants with amblyopia showed reduced illusion strength during amblyopic eye viewing (P = 0.044) with the flash leading.
Amblyopia is associated with the widening of the temporal binding window, specifically for fission when viewing binocularly with the beep leading. This suggests a developmental adaptation to delayed amblyopic eye visual processing to optimize audiovisual integration.
Single-unit recordings have identified a region in the posterior parietal cortex (PPC) of the monkey that represents and updates visual space in a gaze-centered frame. Here, using event-related ...functional magnetic resonance imaging, we identified an analogous bilateral region in the human PPC that shows contralateral topography for memory-guided eye movements and arm movements. Furthermore, when eye movements reversed the remembered horizontal target location relative to the gaze fixation point, this PPC region exchanged activity across the two cortical lobules. This shows that the human PPC dynamically updates the spatial goals for action in a gaze-centered frame.
Amblyopia is a developmental visual impairment that is increasingly recognized to affect higher-level perceptual and multisensory processes. To further investigate the audiovisual (AV) perceptual ...impairments associated with this condition, we characterized the temporal interval in which asynchronous auditory and visual stimuli are perceived as simultaneous 50% of the time (i.e., the AV simultaneity window). Adults with unilateral amblyopia (n = 17) and visually normal controls (n = 17) judged the simultaneity of a flash and a click presented with both eyes viewing. The signal onset asynchrony (SOA) varied from 0 ms to 450 ms for auditory-lead and visual-lead conditions. A subset of participants with amblyopia (n = 6) was tested monocularly. Compared to the control group, the auditory-lead side of the AV simultaneity window was widened by 48 ms (36%; p = 0.002), whereas that of the visual-lead side was widened by 86 ms (37%; p = 0.02). The overall mean window width was 500 ms, compared to 366 ms among controls (37% wider; p = 0.002). Among participants with amblyopia, the simultaneity window parameters were unchanged by viewing condition, but subgroup analysis revealed differential effects on the parameters by amblyopia severity, etiology, and foveal suppression status. Possible mechanisms to explain these findings include visual temporal uncertainty, interocular perceptual latency asymmetry, and disruption of normal developmental tuning of sensitivity to audiovisual asynchrony.
The postillumination pupil response (PIPR) is produced by intrinsically photosensitive retinal ganglion cells (ipRGCs). We aimed to refine the testing conditions for PIPR by investigating whether a ...greater PIPR can be induced using full-field light stimuli of shorter duration and lower intensity than that produced by existing protocols that use central-field stimuli.
Pupil response was recorded with an eye tracker in 10 visually-normal subjects. Red and blue light stimuli were presented using a Ganzfeld system. In Experiment 1 (intensity trials), PIPR was induced using 1-second full-field stimuli of increasing intensities from 0.1 to 400 cd/m(2) (11 steps). For comparison, PIPR also was induced using a 60° × 90° central-field blue stimulus of 400 cd/m(2). In Experiment 2 (duration trials), PIPR was induced using 100 and 400 cd/m(2) full-field stimulus of increasing duration from 4 to 1000 ms (10 steps).
Results indicated that PIPR increased monotonically with increasing stimulus intensity. Full-field stimulation using blue light at 400 cd/m(2) intensity induced significantly more sustained PIPR than central-field stimulation (P = 0.001). In addition, PIPR increased as the stimulus duration increased from 4 to 200 ms; however, no further increase in PIPR was observed when the duration increased from 400 to 1000 ms.
Compared to existing central-field protocols, larger PIPR can be induced with a full-field stimulus with lower intensity and shorter duration, indicating that PIPR is a function of stimulus intensity, stimulus duration, and retinal area stimulated. The testing protocol can be refined with this new knowledge to target particular clinical populations.
It has previously been shown that anisometropic amblyopia affects the programming and execution of saccades. The aim of the current study was to investigate the impact of strabismic amblyopia on ...saccade performance.
Fourteen adults with strabismic amblyopia, 13 adults with strabismus without amblyopia, and 14 visually normal adults performed saccades and reach-to-touch movements to targets presented at ± 5° and ± 10° eccentricity during binocular and monocular viewing. Latency, amplitude, and peak velocity of primary and secondary saccades were measured.
In contrast to visually normal participants who had shorter primary saccade latency during binocular viewing, no binocular advantage was found in patients with strabismus with or without amblyopia. Patients with amblyopia had longer saccade latency during amblyopic eye viewing (P < 0.0001); however, there were no significant differences in saccade amplitude precision among the three groups across viewing conditions. Further analysis showed that only patients with severe amblyopia and no stereopsis (n = 4) exhibited longer latency (which was more pronounced for more central targets; P < 0.0001), and they also had reduced amplitude precision during amblyopic eye viewing. In contrast, patients with mild amblyopia (n = 5) and no stereopsis had normal latency and reduced precision during amblyopic eye viewing (P < 0.001), whereas those with gross stereopsis (n = 5) had normal latency and precision. There were no differences in peak velocity among the groups.
Distinct patterns of saccade performance according to different levels of visual acuity and stereoscopic losses in strabismic amblyopia were found. These findings were in contrast to those in anisometropic amblyopia in which the altered saccade performance was independent of the extent of visual acuity or stereoscopic deficits. These results were most likely due to different long-term sensory suppression mechanisms in strabismic versus anisometropic amblyopia.
To examine the effects of impaired spatiotemporal vision on reaching movements in participants with strabismic amblyopia and to compare their performance to those with strabismus only without ...amblyopia and to visually normal participants.
Sixteen adults with strabismic amblyopia, 14 adults with strabismus only, and 16 visually normal adults were recruited. Participants executed reach-to-touch movements toward targets presented randomly 5° or 10° to the left or right of central fixation in three viewing conditions: both eyes, monocular amblyopic eye (nondominant eye for participants without amblyopia), and monocular fellow eye (dominant eye for participants without amblyopia). Visual feedback of the target was removed on 50% of the trials at the initiation of reaching.
Both groups with abnormal binocular vision (strabismic amblyopia and strabismus only) had reach latency, accuracy, and precision comparable to visually normal participants when viewing with both eyes and fellow (dominant) eye. Latencies were significantly delayed by more than 30 ms in all participants with reduced binocularity during amblyopic eye or nondominant eye viewing compared with controls (P < 0.0001). Participants with strabismic amblyopia and negative stereopsis also had reduced reach precision (i.e., increased variability) during amblyopic eye viewing. In contrast, participants with strabismus only and negative stereopsis had comparable precision across all viewing conditions. Participants with strabismus only and those with strabismic amblyopia used a similar motor strategy; regardless of viewing condition, reach peak acceleration was significantly reduced (P < 0.05) and the duration of acceleration phase was extended in comparison with visually normal participants. There were no significant differences for the deceleration phase.
Participants with strabismic amblyopia and those with strabismus only attain relatively normal reach accuracy and precision. However, they use a different reach strategy that involves changing the motor plan. A similar compensatory strategy was reported previously in participants with anisometropic amblyopia. Our results provide further support that normal binocular vision during development provides important input for the development of visually guided reaching movements.
To investigate the chromatic characteristics and intensity-response function of light-induced reflex lacrimation and its correlation with the melanopsin-driven postillumination pupil response (PIPR).
...Eleven visually normal participants completed the experiment. Lacrimation was measured in one eye by placing a calibrated filter paper strip in the conjunctival sac over a 1 minute-interval (Schirmer's test) during which participants received either no light stimulation (baseline trial) or one flash of blue or red light stimuli presented binocularly with a Ganzfeld stimulator, while the pupil response was recorded simultaneously from the fellow eye by using an eye tracker. Light stimulation trials were presented in alternating fashion at seven incremental intensity steps (0.1, 1, 3.16, 10, 31.6, 100, and 400 cd/m2). Postillumination pupil response was defined as the mean pupil constriction from 10 to 30 seconds post illumination.
The amount of lacrimation in response to 10 to 400 cd/m2 blue light was significantly greater than baseline and increased monotonically with increasing light intensity. Red light did not induce significant reflex lacrimation until the brightest stimulation at 400 cd/m2. There was a positive linear correlation between PIPR and lacrimation in response to blue light (r = 0.74, P < 0.001) but not to red light (r = 0.13, P = 0.25).
The chromatic characteristics and intensity-response of light-induced lacrimation are highly consistent with the features of melanopsin phototransduction. This finding is the first in vivo evidence in humans, supporting the hypothesis that light-induced reflex lacrimation is mediated primarily by melanopsin photoactivity, and provides new insight into the putative mechanisms of photophobia.
Several behavioral studies have shown that the reaction times of visually guided movements are slower in people with amblyopia, particularly during amblyopic eye viewing. Here, we tested the ...hypothesis that the initiation of smooth pursuit eye movements, which are responsible for accurately keeping moving objects on the fovea, is delayed in people with anisometropic amblyopia.
Eleven participants with anisometropic amblyopia and 14 visually normal observers were asked to track a step-ramp target moving at ±15°/s horizontally as quickly and as accurately as possible. The experiment was conducted under three viewing conditions: amblyopic/nondominant eye, binocular, and fellow/dominant eye viewing. Outcome measures were smooth pursuit latency, open-loop gain, steady state gain, and catch-up saccade frequency.
Participants with anisometropic amblyopia initiated smooth pursuit significantly slower during amblyopic eye viewing (206 ± 20 ms) than visually normal observers viewing with their nondominant eye (183 ± 17 ms, P = 0.002). However, mean pursuit latency in the anisometropic amblyopia group during binocular and monocular fellow eye viewing was comparable to the visually normal group. Mean open-loop gain, steady state gain, and catch-up saccade frequency were similar between the two groups, but participants with anisometropic amblyopia exhibited more variable steady state gain (P = 0.045).
This study provides evidence of temporally delayed smooth pursuit initiation in anisometropic amblyopia. After initiation, the smooth pursuit velocity profile in anisometropic amblyopia participants is similar to visually normal controls. This finding differs from what has been observed previously in participants with strabismic amblyopia who exhibit reduced smooth pursuit velocity gains with more catch-up saccades.
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