Brendan T. Barrett

Understanding the Neural Basis of Amblyopia

Amblyopia is the condition in which reduced visual function exists despite full optical correction and an absence of observable ocular pathology. Investigation of the underlying neurology of this condition began in earnest around 40 years ago with the pioneering studies conducted by Hubel and Wiesel. Their early work on the impact of monocular deprivation and strabismus initiated what is now a rapidly developing field of cortical plasticity research. Although the monocular deprivation paradigm originated by Hubel and Wiesel remains a key experimental manipulation in studies of cortical plasticity, somewhat ironically, the neurology underlying the human conditions of strabismus and amblyopia that motivated this early work remains elusive. In this review, the authors combine contemporary research on plasticity and development with data from human and animal investigations of amblyopic populations to assess what is known and to reexamine some of the key assumptions about human amblyopia.

Motion-Sensitive Neurones in V5/MT Modulate Perceived Spatial Position

Until recently, it was widely believed that object position and object motion were represented independently in the visual cortex. However, several studies have shown that adaptation to motion produces substantial shifts in the perceived position of subsequently viewed stationary objects. Two stages of motion adaptation have been proposed: an initial stage at the level of V1 and a secondary stage thought to be located in V5/MT. Indeed, selective adaptation can be demonstrated at each of these levels of motion analysis. What remains unknown is which of these cortical sites are involved in modulating the positional representation of subsequently viewed objects. To answer this question directly, we disrupted cortical activity by using transcranial magnetic stimulation (TMS) immediately after motion adaptation. When TMS was delivered to V5/MT after motion adaptation, the perceived offset of the test stimulus was greatly reduced. In marked contrast, TMS of V1 had no effect on the changes that normally occur in perceived position after motion adaptation. This result demonstrates that the anatomical locus at which motion and positional information interact is area V5/MT rather than V1/V2.

A critical evaluation of the evidence supporting the practice of behavioural vision therapy

In 2000, the UK’s College of Optometrists commissioned a report to critically evaluate the theory and practice of behavioural optometry. The report which followed Jennings (2000 ; Behavioural optometry – a critical review. Optom. Pract. 1: 67) concluded that there was a lack of controlled clinical trials to support behavioural management strategies. The purpose of this report was to evaluate the evidence in support of behavioural approaches as it stands in 2008. The available evidence was reviewed under 10 headings, selected because they represent patient groups/conditions that behavioural optometrists are treating, or because they represent approaches to treatment that have been advocated in the behavioural literature. The headings selected were: (1) vision therapy for accommodation/vergence disorders; (2) the underachieving child; (3) prisms for near binocular disorders and for producing postural change; (4) near point stress and low‐plus prescriptions; (5) use of low‐plus lenses at near to slow the progression of myopia; (6) therapy to reduce myopia; (7) behavioural approaches to the treatment of strabismus and amblyopia; (8) training central and peripheral awareness and syntonics; (9) sports vision therapy; (10) neurological disorders and neuro‐rehabilitation after trauma/stroke. There is a continued paucity of controlled trials in the literature to support behavioural optometry approaches. Although there are areas where the available evidence is consistent with claims made by behavioural optometrists (most notably in relation to the treatment of convergence insufficiency, the use of yoked prisms in neurological patients, and in vision rehabilitation after brain disease/injury), a large majority of behavioural management approaches are not evidence‐based, and thus cannot be advocated.

Induced Deficits in Speed Perception by Transcranial Magnetic Stimulation of Human Cortical Areas V5/MT+ and V3A

In this report, we evaluate the role of visual areas responsive to motion in the human brain in the perception of stimulus speed. We first identified and localized V1, V3A, and V5/MT+ in individual participants on the basis of blood oxygenation level-dependent responses obtained in retinotopic mapping experiments and responses to moving gratings. Repetitive transcranial magnetic stimulation (rTMS) was then used to disrupt the normal functioning of the previously localized visual areas in each participant. During the rTMS application, participants were required to perform delayed discrimination of the speed of drifting or spatial frequency of static gratings. The application of rTMS to areas V5/MT and V3A induced a subjective slowing of visual stimuli and (often) caused increases in speed discrimination thresholds. Deficits in spatial frequency discrimination were not observed for applications of rTMS to V3A or V5/MT+. The induced deficits in speed perception were also specific to the cortical site of TMS delivery. The application of TMS to regions of the cortex adjacent to V5/MT and V3A, as well as to area V1, produced no deficits in speed perception. These results suggest that, in addition to area V5/MT+, V3A plays an important role in a cortical network that underpins the perception of stimulus speed in the human brain.

Centroid Analysis Predicts Visual Localization of First- and Second-order Stimuli

Perceived alignment of asymmetric Gaussian-windowed stimuli was measured in an attempt to differentiate between stimulus characteristics which might underlie visual localization. These asymmetric stimuli have the advantage of being continuous in the spatial domain and of possessing well-defined spatial characteristics in which centroid, points of inflexion and peak can be separated from each other. Results for both luminance- and contrast-defined stimuli are reasonably well described on the basis that the centroid of the stimulus envelope represents the primitive which determines perceived visual location. Centroid location is inherent in the output of filters which are large enough to cover the object of interest.

Severe loss of positional information when detecting deviations in multiple trajectories

Human observers can simultaneously track up to five targets in motion (Z. W. Pylyshyn & R. W. Storm, 1988). We examined the precision for detecting deviations in linear trajectories by measuring deviation thresholds as a function of the number of trajectories (T ). When all trajectories in the stimulus undergo the same deviation, thresholds are uninfluenced by T for T <or= 10. When only one of the trajectories undergoes a deviation, thresholds rise steeply as T is increased [e.g., 3.3 degrees (T = 1), 12.3 degrees (T = 2), 32.9 degrees (T = 4) for one observer]; observers are unable to simultaneously process more than one trajectory in our threshold-measuring paradigm. When the deviating trajectory is cued (e.g., using a different color), varying T has little influence on deviation threshold. The use of a different color for each trajectory does not facilitate deviation detection. Our current data suggest that for deviations that have low discriminability (i.e., close to threshold) the number of trajectories that can be monitored effectively is close to one. In contrast, when the stimuli containing highly discriminable (i.e., substantially suprathreshold) deviations are used, as many as three or four trajectories can be simultaneously monitored (S. P. Tripathy, 2003). Our results highlight a severe loss of positional information when attempting to track multiple objects, particularly in a threshold paradigm.

Changes to Control of Adaptive Gait in Individuals with Long-standing Reduced Stereoacuity

PURPOSE Gait during obstacle negotiation is adapted in visually normal subjects whose vision is temporarily and unilaterally blurred or occluded. This study was conducted to examine whether gait parameters in individuals with long-standing deficient stereopsis are similarly adapted. METHODS Twelve visually normal subjects and 16 individuals with deficient stereopsis due to amblyopia and/or its associated conditions negotiated floor-based obstacles of different heights (7-22 cm). Trials were conducted during binocular viewing and monocular occlusion. Analyses focused on foot placement before the obstacle and toe clearance over it. RESULTS Across all viewing conditions, there were significant group-by-obstacle height interactions for toe clearance (P < 0.001), walking velocity (P = 0.003), and penultimate step length (P = 0.022). Toe clearance decreased (approximately 0.7 cm) with increasing obstacle height in visually normal subjects, but it increased (approximately 1.5 cm) with increasing obstacle height in the stereo-deficient group. Walking velocity and penultimate step length decreased with increasing obstacle height in both groups, but the reduction was more pronounced in stereo-deficient individuals. Post hoc analyses indicated group differences in toe clearance and penultimate step length when negotiating the highest obstacle (P < 0.05). CONCLUSIONS Occlusion of either eye caused significant and similar gait changes in both groups, suggesting that in stereo-deficient individuals, as in visually normal subjects, both eyes contribute usefully to the execution of adaptive gait. Under monocular and binocular viewing, obstacle-crossing performance in stereo-deficient individuals was more cautious when compared with that of visually normal subjects, but this difference became evident only when the subjects were negotiating higher obstacles; suggesting that such individuals may be at greater risk of tripping or falling during everyday locomotion.

Anterior chamber depth measurement in clinical practice.

This study compares the validity of anterior chamber depth estimates provided by a slit-lamp technique with those obtained from pachometry and ultrasonography. The technique provides depth estimates which are valid to within ±0.33 mm relative to standard pachometry, and to within ±0.42 mm relative to ultrasonography. The technique is simple to perform, requires no extra slit-lamp attachments, and may be carried out on any slit-lamp which has a calibrated variable length of slit.

Isolation of stimulus characteristics contributing to Weber's law for position

To examine the independent contribution of various stimulus characteristics to positional judgements, we measured vernier alignment performance for three types of Gabor stimuli. In one, only the contrast envelope of the upper and lower stimulus elements was offset, with the luminance-modulated carrier grating remaining in alignment. In the second, only the carrier grating was offset. In the third, both carrier and envelope were offset together. Performance was examined over a range of element separations. When both cues are available, thresholds for small separations are dominated by carrier offset information and are inversely proportional to carrier frequency. At large separations, thresholds are governed by the spatial scale characteristics of the envelope. For broad-band stimuli such as lines, bars or dots typically used for vernier acuity, their higher frequency content can be used when separations are small, but as separation increases a smooth transition between the scales that determine threshold results in the continuum known as Webers law for position. That is, with increasing separation, larger scales must be used, and thresholds increase in direct proportion to 1/frequency.

Bilateral Changes in Foveal Structure in Individuals with Amblyopia

PURPOSE To examine foveal structure in amblyopia using spectral-domain optical coherence tomography (SD-OCT). DESIGN Prospective, cross-sectional study. PARTICIPANTS AND CONTROLS Two subject groups were recruited to the study: 85 amblyopes (34 adults, 51 children) and 110 visually normal controls (44 adults, 66 children). METHODS A detailed eye examination, including an SD-OCT scan, was performed in all participants. A total of 390 eyes of 195 subjects were imaged using a 3-dimensional (3D) macula scan covering a nominal 6 × 6-mm area with a resolution of 256 × 256 (65,536 axial scans). Data from the B-scans bisecting the fovea both horizontally and vertically were fitted with a mathematical model of the fovea to determine a range of foveal parameters. MAIN OUTCOME MEASURES Foveal thickness, foveal pit depth, and foveal pit slope. RESULTS Bilateral differences between the eyes of amblyopes compared with visually normal controls were found. The difference between foveal structure in amblyopic participants relative to structure in subjects with normal vision persisted even when variables such as age, ethnicity, axial length, and sex were taken into account. Amblyopes showed increased foveal thickness (+8.31 μm; P = 0.006) and a reduction in pit depth in the horizontal meridian (-10.06 μm; P = 0.005) but not in the vertical meridian (P = 0.082) when compared with subjects with normal vision. Foveal pit slopes were found to be approximately 1 degree flatter in the nasal (P = 0.033) and temporal (P = 0.014) meridians in amblyopes, but differences between amblyopes and controls in the superior (P = 0.061) and inferior (P = 0.087) meridians did not reach statistical significance. No statistically significant interocular differences were found in the foveal structure between amblyopic and fellow eyes. CONCLUSIONS Differences were found in the foveal structure in both eyes of amblyopes compared with subjects with normal vision. These differences consisted of increased foveal thickness, reduced pit depth when measured along the horizontal meridian, and flattening of the nasal and temporal sides of the foveal pit.