Herbert C. Goltz

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.

Amblyopia is a neuro-developmental disorder involving a decrease in visual acuity that cannot be explained by ocular abnormalities. It affects 2-3% of the population and is the prevalent cause of monocular blindness. Patching of the amblyopic eye is a powerful treatment in early childhood but its effectiveness decreases with age, which has been attributed to decreased plasticity in the adult brain. In the last few decades new treatment methods including dichoptic training, perceptual learning and video games, were developed that improved visual acuity and/or stereoacuity in adult amblyopia. To understand the factors involved in adult plasticity in amblyopia, its clinical significance and to compare the treatments, we have used mean and individual participant data (IPD) meta-analyses on 19 studies with close to 200 individual scores. Our analysis showed that the average improvement in visual acuity (0.19 logMAR) was above mean test-retest reliability for acuity tests (0.14 logMAR) with 67% of subjects improving by more than this amount. Moreover, half of the subjects improved their stereo acuity by 2 octaves or more. The most important factor was the severity of amblyopia at the onset of treatment. Subjects with more severe amblyopia improved more on visual acuity and less on stereo sensitivity than those with the milder condition. Better binocularity was a predictor of improvements in stereo sensitivity. The different treatments, though employing very diverse strategies, yielded largely similar degrees of improvement on both measures. This suggests that any task involving sufficient engagement of the amblyopic eye could induce plasticity. We interpret this effect as the result of improvement in visual attention to the input from the amblyopic eye. Interocular suppression, which leads to amblyopia, could occur due to signal modulation by visual attention. Forcing visual attention to favor the amblyopic eye’s input might release those suppressive influences, thus improving visual function. Meeting abstract presented at VSS 2015

Introduction: Amblyopia is a developmental visual impairment resulting from abnormal visual experience in childhood. While it used to be thought of as a low-level sensory disorder, recent studies have shown higher-level perceptual deficits. This study will define the temporal and spatial characteristics of audiovisual sensory binding, and will employ the Ventriloquism Effect to determine the relative weighting of audition and vision in spatial localization in amblyopia compared to visually normal controls. Methods: Participants with amblyopia (n=4) and normal controls (n=12) judged simultaneity of acoustic and visual signals at 13 levels of onset asynchrony, and judged co-localization of acoustic and visual signals at 9 levels of horizontal spatial separation. Point of subjective equality and precision for unimodal (auditory or visual) and bimodal (audiovisual) spatial localization was determined using a 2-AFC task. Auditory stimuli were click trains with perceived position controlled by interaural level difference. Visual stimuli were Gaussian blobs flashed on a large LED screen. Spatial reliability of the visual signal was manipulated by changing the Gaussian blob size. All experiments were carried out in a dark acoustic chamber under binocular viewing conditions. Results: Participants with amblyopia perceived audiovisual simultaneity over a significantly broader range of signal onset asynchrony than normal controls, particularly when the visual signal occurred first. Unimodal and bimodal spatial localization precision was lower in participants with amblyopia than in controls at every Gaussian blob size. Both participant groups demonstrated superior spatial localization precision for bimodal stimuli than for either of the component unimodal stimuli. Conclusion: Participants with amblyopia appear to have diminished ability to detect audiovisual asynchrony and reduced precision in visual spatial localization, even when viewing binocularly. Similar to visually normal controls, however, they appear to integrate visual and auditory spatial signals to achieve a ‘bimodal advantage’ to enhance localization precision of bimodal stimuli. Meeting presented at VSS 2015

Amblyopia is a neurodevelopmental disorder defined as a reduction in visual acuity that cannot be corrected by optical means. It has been associated primarily with other low level visual deficits such as reduced contrast sensitivity at high spatial frequencies and increased visual crowding. Research in the last decade demonstrated that amblyopia is also linked to higher-level deficits in global shape and motion perception and in contour integration. Deficits in visual attention have also been shown in counting briefly presented items, tracking objects and identifying items presented in rapid succession. Here, we demonstrated that amblyopia causes more general attentional deficits as manifested in visual search. We compared the performance of subjects with amblyopia (n=9) to those of controls (n=12) on a feature search and a conjunction search with Gabor patches. Eye movements were recorded and controlled by continuous fixation. To account for the low level deficits inherent in amblyopia, we first measured each subjects’ contrast and crowding thresholds and then presented the display elements at suprathreshold levels such that visibility was equalized across the control and the experimental groups. The effectiveness of these precautions at eliminating low-level deficits as a confounding factor was confirmed by the results of the feature search task. Performance on this “pop-out” search, considered to be pre-attentive, was not significantly different between the two groups. In contrast, reaction times on conjunction search, a task requiring the engagement of visual attention, were significantly greater (by as much as 400 msec) in amblyopic eyes than in control or fellow eyes. Taken together, these data suggest that amblyopia is linked to greater and more generalized attentional deficits than previously known. Visual search is a necessary, basic component of everyday functioning and these deficits may result in significant repercussions for people with amblyopia. Meeting presented at VSS 2015

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

Purpose.: Using visual feedback to modify sensorimotor output in response to changes in the external environment is essential for daily function. Prism adaptation is a well-established experimental paradigm to quantify sensorimotor adaptation; that is, how the sensorimotor system adapts to an optically-altered visuospatial environment. Amblyopia is a neurodevelopmental disorder characterized by spatiotemporal deficits in vision that impacts manual and oculomotor function. This study explored the effects of anisometropic amblyopia on prism adaptation. Methods.: Eight participants with anisometropic amblyopia and 11 visually-normal adults, all right-handed, were tested. Participants pointed to visual targets and were presented with feedback of hand position near the terminus of limb movement in three blocks: baseline, adaptation, and deadaptation. Adaptation was induced by viewing with binocular 11.4° (20 prism diopter [PD]) left-shifting prisms. All tasks were performed during binocular viewing. Results.: Participants with anisometropic amblyopia required significantly more trials (i.e., increased time constant) to adapt to prismatic optical displacement than visually-normal controls. During the rapid error correction phase of adaptation, people with anisometropic amblyopia also exhibited greater variance in motor output than visually-normal controls. Conclusions.: Amblyopia impacts on the ability to adapt the sensorimotor system to an optically-displaced visual environment. The increased time constant and greater variance in motor output during the rapid error correction phase of adaptation may indicate deficits in processing of visual information as a result of degraded spatiotemporal vision in amblyopia.

Purpose: The McGurk effect is an audiovisual illusion that involves the concurrent presentation of a phoneme (auditory syllable) and an incongruent viseme (visual syllable). Adults with amblyopia show less susceptibility to this illusion than visually normal controls, even when viewing binocularly. The present study investigated the developmental trajectory of McGurk effect susceptibility in adults, older children (10-17 years), and younger children (4-9 years) with amblyopia. Methods: Sixty-two participants with amblyopia (22 adults, 12 older children, 28 younger children) and 66 visually normal controls (25 adults, 17 older children, 24 younger children) viewed videos that combined phonemes and visemes, and were asked to report what they heard. Videos with both congruent (auditory and visual matching) and incongruent (auditory and visual not matching) stimuli were presented. Incorrect responses on incongruent trials correspond to high McGurk effect susceptibility, indicating that the viseme influenced the phoneme. Results: Participants with amblyopia (28.0% ± 3.3%) demonstrated a less consistent McGurk effect than visually normal controls (15.2% ± 2.3%) across all age groups (p=0.0024). Effect susceptibility increased with age (p=0.0003) for both amblyopic participants and controls. Both groups showed a similar response pattern to different speakers and syllables, but amblyopic participants invariably demonstrated a less consistent effect. Conclusions: Amblyopia is associated with reduced McGurk effect susceptibility in both children and adults. Our findings indicate that the differences do not simply indicate delayed development in children with amblyopia; rather they represent permanent alterations that persist into adulthood.

Purpose. To evaluate the test-retest reliability of current methods of inducing the melanopsin-driven post-illumination pupil response (PIPR) under hemifield, central-field and full-field stimulation conditions. Methods. Pupil response was recorded with an eye tracker in 10 visually normal participants. Light stimuli were presented using a Ganzfeld screen with a custom-built device that allows specific regions of the retina to be stimulated. Blue light stimulation at 400 cd/m2 intensity was presented for 400 ms to the lower and upper halves of the central 30° fields (hemifields), central 30° field (central-field) and full-field to induce PIPR. Red light full-field stimulation was also presented with the same intensity and duration as a control condition. Test-retest reliability of the PIPR measures were assessed by calculating the intra-class correlation coefficient (ICC) of 6 repetitions for lower and upper hemifield stimulation, and 3 repetitions for central-field and full-field stimulation. Results. Hemifield, central-field, and full-field blue light stimulation induced increasingly greater PIPR in ascending order, while full-field red light stimulation induced no PIPR. Mean lower and upper hemifield PIPR were highly symmetric. Mean ICC of blue light PIPR was 0.87 for lower hemifield, 0.88 for upper hemifield, 0.95 for central-field, and 0.94 for full-field stimulation. Conclusions. We validated a new and repeatable method to measure PIPR induced by hemifield, central-field and full-field light stimulation. Good PIPR measurement reliability was obtained under all conditions. This practical and reliable protocol will facilitate the clinical application of PIPR testing in different disease populations.

Purpose. Saccadic adaptation is affected by the spatial variability of the adapting error signal. Recently, we have shown that saccadic adaptation is reduced in anisometropic amblyopia, possibly impacted by spatially imprecise saccades. Here, we tested this idea by quantifying the saccadic endpoint variability difference between people with anisometropic amblyopia and visually normal individuals. We then applied this difference to the second target step distribution during saccadic adaptation in visually normal people to test whether their performance diminished to a similar extent as participants with amblyopia. Methods. Ten visually normal adults performed a double-step adaptation task (±19°, followed by 4° back-steps) with the nondominant eye under two conditions: “consistent error,” using a constant back-step; and “variable error,” using a variable (σ_diff) back-step determined by subtracting the saccadic endpoint variability in controls from that in anisometropic amblyopia during amblyopic/nondominant eye viewing. Percentage change in saccadic gains, percentage retention, and adaptation time constants were analyzed. Results. Percentage change in saccadic gains decreased significantly during the variable error condition (50% ± 10%) compared to the consistent error condition (69% ± 9%; P = 0.0008). Percentage retention and time constants did not differ between conditions. The adaptation magnitude during the variable error condition was comparable to the previous percentage adaptation in people with anisometropic amblyopia during the consistent error condition with amblyopic eye viewing. Conclusions. Our findings indicate that adding exogenous spatial noise to the adapting step consistent with the saccadic endpoint variability difference between amblyopic and visually normal groups is sufficient to reduce saccadic adaptation in healthy individuals.