Amblyopic Deficit Research Articles

Fellow Eye Deficits in Amblyopia

ABSTRACTAmblyopia is a neurodevelopmental disorder of the visual system, as a result of discordant visual experience during infancy or early childhood. Because amblyopia is typically defined as monocularly reduced visual acuity accompanied by one or more known amblyogenic factors, it is often assumed that the fellow eye is normal and sufficient for tasks like reading and eye-hand coordination. Recent scientific evidence of ocular motor, visual, and visuomotor deficits that are present with fellow eye monocular viewing and with binocular viewing calls this assumption into question. This clinical update reviews the research that has revealed fellow ocular motor and visual deficits and the effect that these deficits have on an amblyopic child’s visuomotor and visuocognitive skills. We need to understand how to prevent and rehabilitate the effects of amblyopia not only on the nonpreferred eye but also on the fellow eye.

Binocular treatment of amblyopia: from the laboratory to clinical trials

Over the last 10 years, numerous psychophysical studies have indicated that binocular mechanisms are structurally intact but functionally suppressed in amblyopia (1-8). Many of these studies have used a contrast balancing approach, whereby the contribution of each eye to binocular vision is equated or “balanced” by presenting higher contrast stimulus elements to the amblyopic eye than the fellow eye (6). Using this approach, the strength of suppression can be quantified by measuring the magnitude of interocular contrast difference required for normal binocular combination. When suppression strength has been correlated with other clinical measures, stronger suppression has been associated with worse stereoacuity and worse amblyopic eye visual acuity indicting a link between the monocular and binocular deficits in amblyopia (5,7).

Reduced response cluster size in early visual areas explains the acuity deficit in amblyopia.

Focal visual stimulation typically results in the activation of a large portion of the early visual cortex. This spread of activity is attributed to long-range lateral interactions. Such long-range interactions may serve to stabilize a visual representation or to simply modulate incoming signals, and any associated dysfunction in long-range activation may reduce sensitivity to visual information in conditions such as amblyopia. We sought to measure the dispersion of cortical activity following local visual stimulation in a group of patients with amblyopia and matched normal. Twenty adult anisometropic amblyopes and 10 normal controls participated in this study. Using a multifocal stimulation, we simultaneously measured cluster sizes to multiple stimulation points in the visual field. We found that the functional MRI (fMRI) response cluster size that corresponded to the fellow eye was significantly larger as opposed to that corresponding to the amblyopic eye and that the fMRI response cluster size at the two more central retinotopic locations correlated with amblyopia acuity deficit. Our results suggest that the amblyopic visual cortex has a diminished long-range communication as evidenced by significantly smaller cluster of activity as measured with fMRI. These results have important implications for models of amblyopia and approaches to treatment.

Unilateral Amblyopia Affects Two Eyes: Fellow Eye Deficits in Amblyopia.

Unilateral amblyopia is a visual disorder that arises after selective disruption of visual input to one eye during critical periods of development. In the clinic, amblyopia is understood as poor visual acuity in an eye that was deprived of pattern vision early in life. By its nature, however, amblyopia has an adverse effect on the development of a binocular visual system and the interactions between signals from two eyes. Visual functions aside from visual acuity are impacted, and many studies have indicated compromised sensitivity in the fellow eye even though it demonstrates normal visual acuity. While these fellow eye deficits have been noted, no overarching theory has been proposed to describe why and under what conditions the fellow eye is impacted by amblyopia. Here, we consider four explanations that may account for decreased fellow eye sensitivity: the fellow eye is adversely impacted by treatment for amblyopia; the maturation of the fellow eye is delayed by amblyopia; fellow eye sensitivity is impacted for visual functions that rely on binocular cortex; and fellow eye deficits reflect an adaptive mechanism that works to equalize the sensitivity of the two eyes. To evaluate these ideas, we describe five visual functions that are commonly reported to be deficient in the amblyopic eye (hyperacuity, contrast sensitivity, spatial integration, global motion, and motion-defined form), and unify the current evidence for fellow eye deficits. Further research targeted at exploring fellow eye deficits in amblyopia will provide us with a broader understanding of normal visual development and how amblyopia impacts the developing visual system.

Can perceptual learning alleviate the global motion direction discrimination deficit in amblyopia?

Can perceptual learning alleviate the global motion direction discrimination deficit in amblyopia?

Prehension of a Flanked Target in Individuals With Amblyopia.

Reduced binocularity is a prominent feature of amblyopia and binocular cues are thought to be important for prehension. We examine prehension in individuals with amblyopia when the target-object was flanked, thus mimicking everyday prehension. Amblyopes (n = 20, 36.4 ± 11.7 years; 6 anisometropic, 3 strabismic, 11 mixed) and visually-healthy controls (n = 20, 27.5 ± 6.3 years) reached forward, grasped, and lifted a cylindrical target-object that was flanked with objects either (lateral) side of the target, or in front and behind it in depth. Only six amblyopes (30%) had measurable stereoacuity. Trials were completed in binocular and monocular viewing, using the better eye in amblyopic participants. Compared with visual normals, amblyopes displayed a longer overall movement time (P = 0.031), lower average reach velocity (P = 0.021), smaller maximum aperture (P = 0.007), and a longer duration between object contact and lift (P = 0.003). Differences between groups were more apparent when the flankers were in front and behind, compared with either side, as evidenced by significant group-by-flanker configuration interactions for reach duration (P < 0.001), size and timing of maximum aperture (P ≤ 0.009), end-of-reach to object-contact (P < 0.001), and object-contact to lift (P = 0.044), suggesting that amblyopic deficits are greatest when binocular cues are richest. Both groups demonstrated a significant binocular advantage, in that in both groups performance was worse for monocular compared with binocular viewing, but interestingly, amblyopic deficits in binocular viewing largely persisted during monocular viewing with the better eye. These results suggest that amblyopes either display considerable residual binocularity or that they have adapted to make good use of their abnormal binocularity.

Is the Cortical Deficit in Amblyopia Due to Reduced Cortical Magnification, Loss of Neural Resolution, or Neural Disorganization?

The neural basis of amblyopia, a visual deficit affecting 3% of the human population, remains a matter of debate. We undertook the first population receptive field functional magnetic resonance imaging analysis in participants with amblyopia and compared the projections from the amblyopic and fellow normal eye in the visual cortex. The projection from the amblyopic eye was found to have a normal cortical magnification factor, enlarged population receptive field sizes, and topographic disorganization in all early visual areas. This is consistent with an explanation of amblyopia as an immature system with a normal complement of cells whose spatial resolution is reduced and whose topographical map is disordered. This bears upon a number of competing theories for the psychophysical defect and affects future treatment therapies.

The effect of occlusion therapy on motion perception deficits in amblyopia

There is growing evidence for deficits in motion perception in amblyopia, but these are rarely assessed clinically. In this prospective study we examined the effect of occlusion therapy on motion-defined form perception and multiple-object tracking. Participants included children (3–10years old) with unilateral anisometropic and/or strabismic amblyopia who were currently undergoing occlusion therapy and age-matched control children with normal vision. At the start of the study, deficits in motion-defined form perception were present in at least one eye in 69% of the children with amblyopia. These deficits were still present at the end of the study in 55% of the amblyopia group. For multiple-object tracking, deficits were present initially in 64% and finally in 55% of the children with amblyopia, even after completion of occlusion therapy. Many of these deficits persisted in spite of an improvement in amblyopic eye visual acuity in response to occlusion therapy. The prevalence of motion perception deficits in amblyopia as well as their resistance to occlusion therapy, support the need for new approaches to amblyopia treatment.

Steady-state contrast response functions provide a sensitive and objective index of amblyopic deficits.

Visual deficits in amblyopia are neural in origin, yet are difficult to characterize with functional magnetic resonance imagery (fMRI). Our aim was to develop an objective electroencephalography (EEG) paradigm that can be used to provide a clinically useful index of amblyopic deficits. We used steady-state visual evoked potentials (SSVEPs) to measure full contrast response functions in both amblyopic (n = 10, strabismic or mixed amblyopia, mean age: 44 years) and control (n = 5, mean age: 31 years) observers, both with and without a dichoptic mask. At the highest target contrast, the ratio of amplitudes across the weaker and stronger eyes was highly correlated (r = 0.76) with the acuity ratio between the eyes. We also found that the contrast response function in the amblyopic eye had both a greatly reduced amplitude and a shallower slope, but that surprisingly dichoptic masking was weaker than in controls. The results were compared with the predictions of a computational model of amblyopia and suggest a modification to the model whereby excitatory (but not suppressive) signals are attenuated in the amblyopic eye. We suggest that SSVEPs offer a sensitive and objective measure of the ocular imbalance in amblyopia and could be used to assess the efficacy of amblyopia therapies currently under development.

Reach-to-precision grasp deficits in amblyopia: Effects of object contrast and low visibility

Adults with a history of unilateral amblyopia and abnormal binocularity have a range of visual deficits, with some of the ‘higher’ levels ones generalizing to their dominant (non-amblyopic) eye and linked to widespread binocular cortical network dysfunctions. Our interests are in how these problems also impact on their hand action control in real-world situations. We investigated whether eye-hand coordination deficits, known to exist in amblyopia when goal objects are presented under full-lighting and at high contrast, are exacerbated under low object-background contrast or in dim lighting/low visibility conditions. Hand movement parameters were recorded and quantified in 13 amblyopia and 13 control subjects while they reached-to-precision grasp objects using both eyes together or just their dominant or amblyopic/non-dominant eye alone under these 3 task conditions. Compared to controls, the amblyopia subjects spent significantly longer in preparing their movements, in the initial (planned) periods of their reach and grasp and in applying their grip, while making more reach and grasp errors under all 3 views and tasks. Deficits in planning and controlling the grasp were also selectively accentuated in the low contrast condition, but with no evidence of relatively worse performance under low environmental illumination. We suggest that the dysfunctions in amblyopia are associated with generalized difficulties in obtaining reliable visual evidence about the target’s 3D properties during movement planning and in selecting and guiding the proper course of action, especially when segregating the object from background is more challenging.

The amblyopic deficit for 2nd order processing: Generality and laterality

A number of previous reports have suggested that the processing of second-order stimuli by the amblyopic eye (AE) is defective and that the fellow non-amblyopic eye (NAE) also exhibits an anomaly. Second-order stimuli involve extra-striate as well as striate processing and provide a means of exploring the extent of the cortical anomaly in amblyopia using psychophysics. We use a range of different second-order stimuli to investigate how general the deficit is for detecting second-order stimuli in adult amblyopes. We compare these results to our previously published adult normative database using the same stimuli and approach to determine the extent to which the detection of these stimuli is defective for both amblyopic and non-amblyopic eye stimulation. The results suggest that the second-order deficit affects a wide range of second-order stimuli, and by implication a large area of extra-striate cortex, both dorsally and ventrally. The NAE is affected only in motion-defined form judgments, suggesting a difference in the degree to which ocular dominance is disrupted in dorsal and ventral extra-striate regions.

P.5.b.004 Association of ankle brachial index among the elderly with normal cognition, amnestic mild cognitive impairment and Alzheimer's disease

Texture segmentation of ‘target’ Gabors from an array of ‘background’ Gabors was measured in terms of the difference in orientation between the two regions, as well as the difference in orientation within each region. Segmentation was shown to occur on the basis of local orientation differences at the boundary between the target and background regions (Nothdurft, H.C. (1992). Feature analysis and the role of similarity in preattentive vision. Perception and Psychophysics, 52, 355–375.). We obtained similar results for both the amblyopic and non-amblyopic eye of three strabismic amblyopes, and showed also that the effects of texture undersampling and positional jitter were similar for the two eyes. This pattern of results is consistent with intact mechanisms of texture perception in amblyopic cortex, and suggests also that any amblyopic deficits in first-order cortical units (undersampling and/or positional uncertainty) do not limit higher-order texture segmentation processes. Therefore, first- and second-order processes involved in perceptual grouping of oriented elements (that appear to be abnormal in amblyopic cortex; Kovács, I., Polat, U., Norcia, A.M. (1996). Breakdown of binding mechanisms in amblyopia. Association for Research in Vision and Ophthalmology Abstracts; Mussap, A.J., Levi, D.M. (1995). Amblyopic deficits in perception of second-order orientation. Investigative Ophthalmology and Visual Science (Supplement), 36, S634; Mussap, A.J., Levi, D.M. (1998). Amblyopic deficits in perceptual grouping. Vision Research, submitted) do not contribute to texture perception based on orientation contrast.

Global processing in amblyopia: a review.

Amblyopia is a neurodevelopmental disorder of the visual system that is associated with disrupted binocular vision during early childhood. There is evidence that the effects of amblyopia extend beyond the primary visual cortex to regions of the dorsal and ventral extra-striate visual cortex involved in visual integration. Here, we review the current literature on global processing deficits in observers with either strabismic, anisometropic, or deprivation amblyopia. A range of global processing tasks have been used to investigate the extent of the cortical deficit in amblyopia including: global motion perception, global form perception, face perception, and biological motion. These tasks appear to be differentially affected by amblyopia. In general, observers with unilateral amblyopia appear to show deficits for local spatial processing and global tasks that require the segregation of signal from noise. In bilateral cases, the global processing deficits are exaggerated, and appear to extend to specialized perceptual systems such as those involved in face processing.

Amblyopic Deficit Beyond the Fovea: Delayed and Variable Single-Trial ERP Response Latencies, but Unaltered Amplitudes

Amblyopia was first described as a deficit of central vision. However, it has long been debated whether this dysfunction is limited to the fovea or whether extrafoveal vision is also affected, as studies concerning the latter are equivocal. The purpose of the study was to resolve this issue. We investigated the amblyopic effect on event-related potentials (ERPs) with foveal and perifoveal stimuli, either matched in size based on cortical magnification or presented as large annular stimuli. In two separate experiments we measured ERPs on amblyopic patients and control subjects using face images. Latency and amplitude of averaged ERPs and their single-trial distributions were analyzed. When the fovea was stimulated, latency and amplitude of the early averaged ERP components increased and were reduced, respectively, in the amblyopic compared with the fellow eye. Importantly, perifoveal stimulation also elicited similar amblyopic deficits, which were clearly significant in the case of using cortical magnification scaled stimuli. However, single-trial peak analysis revealed that foveal and perifoveal effects differed in nature: Peak amplitudes were reduced only in foveal stimulation, while latencies were delayed and jittered at both the fovea and perifovea. Event-related potentials obtained from fellow eyes were not significantly different from those of normal observers. Our findings revealed the existence of amblyopic deficits at the perifovea when the stimulated cortical area was matched in size to that of foveal stimulation. These deficits manifested themselves only in the temporal structure of the responses, unlike foveal deficits, which affected both component amplitude and latency.

The Effects of Blur and Eccentric Viewing on Adult Acuity for Pediatric Tests: Implications for Amblyopia Detection

The detection of amblyopia in children relies on an accurate assessment of visual acuity. Visual deficits in anisometropic and strabismic amblyopia are different, but the influence of chart design, in particular position, and type of crowding features on visual acuity in the two types of amblyopia, is not clear. Certain aspects of amblyopic spatial vision are mimicked in healthy individuals by imposing increasing levels of blur and retinal eccentricity. We measured the effects of these conditions on visual acuity in healthy adults, with crowded and uncrowded vision tests. Visual acuity was measured under conditions of blur (0-4 D) and eccentric viewing (0-5 degrees) using high-contrast optotypes derived from common children's acuity charts. Optotypes were presented in isolation, in commercially available crowded configurations, and in configurations with closer target-flanker separations than those currently available. Dioptric blur had similar degradative effects on crowded and isolated visual acuity (P > 0.05), whereas eccentric viewing resulted in a larger deterioration of visual acuity for crowded tests (E2 of 0.86-1.06) than for isolated optotypes (E2 of 1.57-1.72) (P < 0.05). Maximum crowding effects occurred for closer target-flanker separations than those currently used commercially. In so far as blur and eccentric viewing mimic spatial acuity deficits in amblyopia, the results suggest that crowded tests might be of limited value in the detection of anisometropic amblyopia, but should be valuable in the detection of strabismic amblyopia. Crowding effects would be greater if flanking features were placed closer to the target than they currently are in commercially available charts.

How the Visual Cortex Handles Stimulus Noise: Insights from Amblyopia

Adding noise to a visual image makes object recognition more effortful and has a widespread effect on human electrophysiological responses. However, visual cortical processes directly involved in handling the stimulus noise have yet to be identified and dissociated from the modulation of the neural responses due to the deteriorated structural information and increased stimulus uncertainty in the case of noisy images. Here we show that the impairment of face gender categorization performance in the case of noisy images in amblyopic patients correlates with amblyopic deficits measured in the noise-induced modulation of the P1/P2 components of single-trial event-related potentials (ERP). On the other hand, the N170 ERP component is similarly affected by the presence of noise in the two eyes and its modulation does not predict the behavioral deficit. These results have revealed that the efficient processing of noisy images depends on the engagement of additional processing resources both at the early, feature-specific as well as later, object-level stages of visual cortical processing reflected in the P1 and P2 ERP components, respectively. Our findings also suggest that noise-induced modulation of the N170 component might reflect diminished face-selective neuronal responses to face images with deteriorated structural information.

The effects of spatial offset, temporal offset and image speed on sensitivity to global motion in human amblyopia

The presence of a general global motion processing deficit in amblyopia is now well established, although its severity may depend on image speed and amblyopia type, but its underlying cause(s) is still largely indeterminate. To address this issue and to characterize further the nature of the global motion perception deficit in human amblyopia, the effects of varying spatial offset (jump size-Δs) and temporal offset (delay between positional updates-Δt) in discriminating global motion for a range of speeds (1.5, 3 and 9°/s) in both amblyopic and normal vision were evaluated. For normal adult observers (NE) and the non-amblyopic eye (FE) motion coherence thresholds measured when Δt was varied were significantly higher than those when Δs was varied. Furthermore when Δt was varied, thresholds rose significantly as the speed of image motion decreased for both NEs and FEs. AE thresholds were higher overall than the other eyes and appeared independent of both the method used to create movement and speed. These results suggest that the spatial and temporal limits underlying the perception of global motion are different. In addition degrading the smoothness of motion has comparatively little effect on the motion mechanisms driven by the AE, suggesting that the internal noise associated with encoding motion direction is relatively high.

Global processing of orientation in amblyopia

We set out to determine whether extra-striate ventral stream function was compromised in amblyopia and to compare any observed deficit with previous data on comparable dorsal stream function. We devised a multi-element orientation task where orientation coherence sensitivity could be measured in a comparable way to motion coherence. The use of spatial frequency narrowband elements allowed for accurate correction of any upstream contrast sensitivity influence and ensured that the orientation bandwidth of our elements did not covary with the measured coherence. Using a standard equivalent noise analysis, we varied both the local orientation bandwidth of individual elements as well as the global orientation bandwidth of the element array to obtain estimates of both local and global internal noise and efficiency. The results show that for this ventral stream task there is only a subtle amblyopic deficit in processing global orientation relative to control observers. This deficit is present for both amblyopic and fixing eyes, and appears to reflect poorer efficiency in processing local orientation, suggesting a subtle deficit at the input stage to extra-striate cortex where orientation coherence is processed.

Assessment of neuroretinal function in a group of functional amblyopes with documented LGN deficits

In this study we examine neuroretinal function in five amblyopes, who had been shown in previous functional MRI (fMRI) studies to have compromised function of the lateral geniculate nucleus (LGN), to determine if the fMRI deficit in amblyopia may have its origin at the retinal level. We used slow flash multifocal ERG (mfERG) and compared averaged five ring responses of the amblyopic and fellow eyes across a 35 deg field. Central responses were also assessed over a field which was about 6.3 deg in diameter. We measured central retinal thickness using optical coherence tomography. Central fields were measured using the MP1-Microperimeter which also assesses ocular fixation during perimetry. MfERG data were compared with fMRI results from a previous study. Amblyopic eyes had reduced response density amplitudes (first major negative to first positive (N1-P1) responses) for the central and paracentral retina (up to 18 deg diameter) but not for the mid-periphery (from 18 to 35 deg). Retinal thickness was within normal limits for all eyes, and not different between amblyopic and fellow eyes. Fixation was maintained within the central 4° more than 80% of the time by four of the five participants; fixation assessed using bivariate contour ellipse areas (BCEA) gave rankings similar to those of the MP-1 system. There was no significant relationship between BCEA and mfERG response for either amblyopic or fellow eye. There was no significant relationship between the central mfERG eye response difference and the selective blood oxygen level dependent (BOLD) LGN eye response difference previously seen in these participants. Retinal responses in amblyopes can be reduced within the central field without an obvious anatomical basis. Additionally, this retinal deficit may not be the reason why the LGN BOLD (blood oxygen level dependent) responses are reduced for amblyopic eye stimulation.

Abnormal Radial Deformation Hyperacuity in Children with Strabismic Amblyopia

In infants and toddlers, letter acuity is not a useful option, and grating acuity may underestimate the depth of strabismic amblyopia. Here, as a first step to establish the effectiveness of the paradigm as a clinical test, we assessed if radial deformation hyperacuity, known to be severely disrupted in adults with strabismic amblyopia, could be a potential test to detect and monitor strabismic amblyopia in young children. Fifty-one strabismic children and 130 normal controls ages 3 to 17 years participated. Radial deformation hyperacuity with three different radial frequency (RF) patterns (1° radius 8 RF, 0.5° radius 8 RF, and 1° radius 16 RF), optotype acuity, and grating acuity were measured. For strabismic children, hyperacuity and grating acuity were identified as normal/amblyopic based on age-matched norms. The normal/abnormal classification was compared with amblyopia diagnosis by gold standard early treatment diabetic retinopathy study (ETDRS) optotype visual acuity. The 0.5° radius 8 RF pattern had 83% sensitivity and 71% positive predictive value (PPV) for strabismic amblyopia. In comparison, the 1° radius 8 RF and 1° radius 16 RF patterns had poorer sensitivity (27%-12%) and PPV (57%-50%) for amblyopia, similar to grating acuity (sensitivity = 38%, PPV = 31%). Amblyopic deficits using the 0.5° radius 8 RF pattern were directly proportional to optotype visual acuity deficits. The demonstrated feasibility of radial deformation stimuli for forced-choice preferential looking testing and the sensitivity and specificity of the small radius radial deformation hyperacuity stimulus for amblyopia support the potential to utilize this test to detect and monitor amblyopia in infants and preschool children.