Binocular summation of contrast remains intact in strabismic amblyopia

PURPOSE. Strabismic amblyopia is typically associated with several visual deficits, including loss of contrast sensitivity in the amblyopic eye and abnormal binocular vision. Binocular summation ratios (BSRs) are usually assessed by comparing contrast sensitivity for binocular stimuli (sens BIN) with that measured in the good eye alone (sensGOOD), giving BSR = sensBIN/sensGOOD. This calculation provides an operational index of clinical binocular function, but does not assess whether neuronal mechanisms for binocular summation of contrast remain intact. This study was conducted to investigate this question. METHODS. Horizontal sine-wave gratings were used as stimuli (3 or 9 cyc/deg; 200 ms), and the conventional method of assessment (above) was compared with one in which the contrast in the amblyopic eye was adjusted (normalized) to equate monocular sensitivities. RESULTS. In nine strabismic amblyopes (mean age, 32 years), the results confirmed that the BSR was close to unity when the conventional method was used (little or no binocular advantage), but increased to approximately √2 or higher when the normalization method was used. The results were similar to those for normal control subjects (n = 3; mean age, 38 years) and were consistent with the physiological summation of contrast between the eyes. When the normal observers performed the experiments with a neutral-density (ND) filter in front of one eye, their performance was similar to that of the amblyopes in both methods of assessment. CONCLUSIONS. The results indicate that strabismic amblyopes have mechanisms for binocular summation of contrast and that the amblyopic deficits of binocularity can be simulated with an ND filter. The implications of these results for best clinical practice are discussed. Copyright © Association for Research in Vision and Ophthalmology.

Contrast masking in strabismic amblyopia: attenuation, noise, interocular suppression and binocular summation

To investigate amblyopic contrast vision at threshold and above we performed pedestal-masking (contrastdiscrimination) experiments with a group of eight strabismic amblyopes using horizontal sinusoidal gratings (mainly 3 c/deg) in monocular, binocular and dichoptic configurations balanced across eye (i.e. five conditions). With some exceptions in some observers, the four main results were as follows. (1) For the monocular and dichoptic conditions, sensitivity was less in the amblyopic eye than in the good eye at all mask contrasts. (2) Binocular and monocular dipper functions superimposed in the good eye. (3) Monocular masking functions had a normal dipper shape in the good eye, but facilitation was diminished in the amblyopic eye. (4) A less consistent result was normal facilitation in dichoptic masking when testing the good eye, but a loss of this when testing the amblyopic eye. This pattern of amblyopic results was replicated in a normal observer by placing a neutral density filter in front of one eye. The two-stage model of binocular contrast gain control [Meese, T.S., Georgeson, M.A. & Baker, D.H. (2006). Binocular contrast vision at and above threshold. Journal of Vision 6, 1224--1243.] was `lesioned' in several ways to assess the form of the amblyopic deficit. The most successful model involves attenuation of signal and an increase in noise in the amblyopic eye, and intact stages of interocular suppression and binocular summation. This implies a behavioural influence from monocular noise in the amblyopic visual system as well as in normal observers with an ND filter over one eye.

Neuroimaging in human amblyopia

Functional magnetic resonance imaging (fMRI), positron emission tomography (PET) and magnetoencephalography (MEG) have been the principal neuroimaging tools used to assess the site and nature of cortical deficits in human amblyopia. A review of this growing body of work is presented here with particular reference to various controversial issues, including whether or not the primary visual cortex is dysfunctional, the involvement of higher-order visual areas, neural differences between strabismic and anisometropic amblyopes, and the effects of modern-day drug treatments. We also present our own recent MEG work in which we used the analysis technique of synthetic aperture magnetometry (SAM) to examine the effects of strabismic amblyopia on cortical function. Our results provide evidence that the neuronal assembly associated with form perception in the extrastriate cortex may be dysfunctional in amblyopia, and that the nature of this dysfunction may relate to a change in the normal temporal pattern of neuronal discharges. Based on these results and existing literature, we conclude that a number of cortical areas show reduced levels of activation in amblyopia, including primary and secondary visual areas and regions within the parieto-occipital cortex and ventral temporal cortex. Copyright © 2006 Taylor & Francis Group, LLC.

Higher-order aberrations in amblyopia:an analysis of pre- and post-wavefront-guided laser refractive correction

For more than a century it has been known that the eye is not a perfect optical system, but rather a system that suffers from aberrations beyond conventional prescriptive descriptions of defocus and astigmatism. Whereas traditional refraction attempts to describe the error of the eye with only two parameters, namely sphere and cylinder, measurements of wavefront aberrations depict the optical error with many more parameters. What remains questionable is the impact these additional parameters have on visual function. Some authors have argued that higher-order aberrations have a considerable effect on visual function and in certain cases this effect is significant enough to induce amblyopia. This has been referred to as ‘higher-order aberration-associated amblyopia’. In such cases, correction of higher-order aberrations would not restore visual function. Others have reported that patients with binocular asymmetric aberrations display an associated unilateral decrease in visual acuity and, if the decline in acuity results from the aberrations alone, such subjects may have been erroneously diagnosed as amblyopes. In these cases, correction of higher-order aberrations would restore visual function. This refractive entity has been termed ‘aberropia’. In order to investigate these hypotheses, the distribution of higher-order aberrations in strabismic, anisometropic and idiopathic amblyopes, and in a group of visual normals, was analysed both before and after wavefront-guided laser refractive correction. The results show: (i) there is no significant asymmetry in higher-order aberrations between amblyopic and fixing eyes prior to laser refractive treatment; (ii) the mean magnitude of higher-order aberrations is similar within the amblyopic and visually normal populations; (iii) a significant improvement in visual acuity can be realised for adult amblyopic patients utilising wavefront-guided laser refractive surgery and a modest increase in contrast sensitivity was observed for the amblyopic eye of anisometropes following treatment (iv) an overall trend towards increased higher-order aberrations following wavefront-guided laser refractive treatment was observed for both visually normal and amblyopic eyes. In conclusion, while the data do not provide any direct evidence for the concepts of either ‘aberropia’ or ‘higher-order aberration-associated amblyopia’, it is clear that gains in visual acuity and contrast sensitivity may be realised following laser refractive treatment of the amblyopic adult eye. Possible mechanisms by which these gains are realised are discussed.

The relationship between fusion, suppression, and diplopia in amblyopia

Purpose: Traditionally, it has been thought that no binocular combination occurs in amblyopia. However, there is a growing body of evidence that there are intact binocular mechanisms in amblyopia rendered inactive under normal viewing conditions due to imbalanced monocular inputs. Georgeson and Wallis (2014) recently introduced a novel method to investigate fusion, suppression and diplopia in normal population. We have modified this method to assess binocular interactions in amblyopia. Methods: Ten amblyopic and ten control subjects viewed briefly-presented (200 ms) pairs of dichoptically separated horizontal Gaussian blurred edges. Subjects reported one central edge, one offset edge, or a double edge as the vertical disparity was manipulated. The experiment was conducted at a range of spatial scales (blur widths of 4, 8, 16, and 32 arc min) and contrasts. Our model, based Georgeson and Wallis (2014), converted subjects’ responses into probabilities of fusion, suppression, and diplopia. Results: When the normal participants were presented equal contrast to each eye the probability of fusion gradually decreased with increasing disparity, as the probability of diplopia gradually increased. In only a small proportion of the trials, normal participants experienced suppression. The pattern was consistent across all edge blurs. Interestingly, the majority of amblyopes had a comparable pattern of fusion, i.e. decreasing probability with increasing disparity. However, with increasing disparity the amblyopes tended to suppress the amblyopic eye, experiencing diplopia only in a small proportion of trials particularly at large blurs. Increasing the interocular contrast offset favouring the amblyopic eye normalized the pattern of data in a way similar to normal participants. There were some interesting exceptions: strong suppressors for which our contrast range was inadequate and one case in which diplopia dominated. Conclusions: This task is suitable for assessing binocular interactions in amblyopic participants and providing a way to quantify the relationship between fusion, suppression and diplopia. In agreement with previous studies, our data indicate the presence of binocular mechanisms in amblyopia. A contrast offset favouring the amblyopic eye normalizes the measured binocular interactions in the amblyopic visual system.

Interocular suppression and contrast gain control in human vision

The human visual system combines contrast information from the two eyes to produce a single cyclopean representation of the external world. This task requires both summation of congruent images and inhibition of incongruent images across the eyes. These processes were explored psychophysically using narrowband sinusoidal grating stimuli. Initial experiments focussed on binocular interactions within a single detecting mechanism, using contrast discrimination and contrast matching tasks. Consistent with previous findings, dichoptic presentation produced greater masking than monocular or binocular presentation. Four computational models were compared, two of which performed well on all data sets. Suppression between mechanisms was then investigated, using orthogonal and oblique stimuli. Two distinct suppressive pathways were identified, corresponding to monocular and dichoptic presentation. Both pathways impact prior to binocular summation of signals, and differ in their strengths, tuning, and response to adaptation, consistent with recent single-cell findings in cat. Strikingly, the magnitude of dichoptic masking was found to be spatiotemporally scale invariant, whereas monocular masking was dependent on stimulus speed. Interocular suppression was further explored using a novel manipulation, whereby stimuli were presented in dichoptic antiphase. Consistent with the predictions of a computational model, this produced weaker masking than in-phase presentation. This allowed the bandwidths of suppression to be measured without the complicating factor of additive combination of mask and test. Finally, contrast vision in strabismic amblyopia was investigated. Although amblyopes are generally believed to have impaired binocular vision, binocular summation was shown to be intact when stimuli were normalized for interocular sensitivity differences. An alternative account of amblyopia was developed, in which signals in the affected eye are subject to attenuation and additive noise prior to binocular combination.

School vision screening, ages 5-16 years:The evidence-base for content, provision and efficacy

The optometric profession in the UK has a major role in the detection, assessment and management of ocular anomalies in children between 5 and 16 years of age. The role complements a variety of associated screening services provided across several health care sectors. The review examines the evidence-base for the content, provision and efficacy of these screening services in terms of the prevalence of anomalies such as refractive error, amblyopia, binocular vision and colour vision and considers the consequences of their curtailment. Vision screening must focus on pre-school children if the aim of the screening is to detect and treat conditions that may lead to amblyopia, whereas if the aim is to detect and correct significant refractive errors (not likely to lead to amblyopia) then it would be expedient for the optometric profession to act as the major provider of refractive (and colour vision) screening at 5-6 years of age. Myopia is the refractive error most likely to develop during primary school presenting typically between 8 and 12 years of age, thus screening at entry to secondary school is warranted. Given the inevitable restriction on resources for health care, establishing screening at 5 and 11 years of age, with exclusion of any subsequent screening, is the preferred option. © 2004 The College of Optometrists.

Community-Based Study of the Association of High Myopia in Children with Ocular and Systemic Disease

Purpose. High myopia in childhood is associated with important ocular and systemic conditions. However in the UK, high myopia in early childhood is not specifically identified in current ophthalmology, optometry, or orthoptic protocols for screening, referral, or investigation. An ongoing study in the West Midlands, UK, is investigating high myopia presenting to community health care clinics with the aim of compiling guidelines for assessment and subsequent referral. Methods. Children with high myopia were identified from community optometric and orthoptic sources and invited for an ophthalmology and optometry examination to ascertain possible ocular or systemic disease. Results. High myopia with no associated ocular or systemic condition was present in 15 (56%) of the children. In seven children (25%), associated ocular problems were found including unrecognized retinal dystrophies and amblyopia. Systemic disorders associated with high myopia were found in five children (19%) and included Sticklers syndrome, Weill-Marchesani syndrome, and homocystinuria. In one child, the diagnosis made before this study was found to be incorrect, and in another child, the results were inconclusive. In two cases, the diagnosis of a systemic condition in the child led to the identification of the disease in at least one relative. Conclusions. There is a high prevalence of ocular and systemic abnormality in young children seen in the community. Optometric and ophthalmologic assessment of children less than 10 years with myopia ≥5 D is likely to identify significant ocular or systemic disease, a proportion of which will respond to medical intervention. Detection and prompt referral of these cases by community health care services may be expected to prolong vision and possibly life expectancy.

Functional neuroimaging and behavioural studies on global form processing in the human visual system

Magnetoencephalography (MEG), functional magnetic resonance imaging (fMRI) and behavioural experiments were used to investigate the neural processes underlying global form perception in human vision. Behavioural studies using Glass patterns examined sensitivity for detecting radial, rotational and horizontal structure. Neuroimaging experiments using either Glass patterns or arrays of Gabor patches determined the spatio-temporal neural responseto global form. MEG data were analysed using synthetic aperture magnetometry (SAM) to spatially map event-related cortical oscillatory power changes: the temporal sequencing of activity within a discrete cortical area was determined using a Morlet wavelet transform. A case study was conducted to determine the effects of strbismic amblyopia on global form processing: all other observers were normally-sighted. The main findings from normally-sighted observers were: 1) sensitivity to horizontal structure was less than for radial or rotational structure; 2) the neural response to global structure was a reduction in cortical oscillatory power (10-30 Hz) within a network of extrastriate areas, including V4 and V3a; 3) the extend of reduced cortical power was least for horizontal patters; 4) V1 was not identified as a region of peak activity with either MEG or fMRI. The main findings with the strabismic amblyope were: 1) sensitivity for detection of radial, rotational, and horizontal structure was reduced when viewed with the amblyopic- relative to the fellow- eye; 2) cortical power changes within V4 to the presentation of rotational Glass patterns were less when viewed with the amblyopic- compared with the fellow- eye. The main conclusions are: 1) a network of extrastriate cortical areas are involved in the analysis of global form, with the most prominent change in neural activity being a reduction in oscillatory power within the 10-30 Hz band; 2) in strabismic amblyopia, the neuronal assembly associated with form perception in extrastriate cortex may be dysfunctional, the nature of this dysfunction may be a change in the normal temporal pattern of neuronal discharges; 3) MEG, fMRI and behavioural measures support the notion that different neural processes underlie the perception of horizontal as opposed to radial or rotational structure.

Clinical studies of spatial and temporal aspects of vision: an investigation using psychophysical and electrophysiological techniques

Separate physiological mechanisms which respond to spatial and temporal stimulation have been identified in the visual system. Some pathological conditions may selectively affect these mechanisms, offering a unique opportunity to investigate how psychophysical and electrophysiological tests reflect these visual processes, and thus enhance the use of the tests in clinical diagnosis. Amblyopia and optical blur were studied, representing spatial visual defects of neural and optical origin, respectively. Selective defects of the visual pathways were also studied - optic neuritis which affects the optic nerve, and dementia of the Alzheimer type in which the higher association areas are believed to be affected, but the primary projections spared. Seventy control subjects from 10 to 79 years of age were investigated. This provided material for an additional study of the effect of age on the psychophysical and electrophysiological responses. Spatial processing was measured by visual acuity, the contrast sensitivity function, or spatial modulation transfer function (MTF), and the pattern reversal and pattern onset-offset visual evoked potential (VEP). Temporal, or luminance, processing was measured by the de Lange curve, or temporal MTF, and the flash VEP. The pattern VEP was shown to reflect the integrity of the optic nerve, geniculo striate pathway and primary projections, and was related to high temporal frequency processing. The individual components of the flash VEP differed in their characteristics. The results suggested that the P2 component reflects the function of the higher association areas and is related to low temporal frequency processing, while the Pl component reflects the primary projection areas. The combination of a delayed flash P2 component and a normal latency pattern VEP appears to be specific to dementia of the Alzheimer type and represents an important diagnostic test for this condition.

Pattern integration in the normal and abnormal human visual system

The processing conducted by the visual system requires the combination of signals that are detected at different locations in the visual field. The processes by which these signals are combined are explored here using psychophysical experiments and computer modelling. Most of the work presented in this thesis is concerned with the summation of contrast over space at detection threshold. Previous investigations of this sort have been confounded by the inhomogeneity in contrast sensitivity across the visual field. Experiments performed in this thesis find that the decline in log contrast sensitivity with eccentricity is bilinear, with an initial steep fall-off followed by a shallower decline. This decline is scale-invariant for spatial frequencies of 0.7 to 4 c/deg. A detailed map of the inhomogeneity is developed, and applied to area summation experiments both by incorporating it into models of the visual system and by using it to compensate stimuli in order to factor out the effects of the inhomogeneity. The results of these area summation experiments show that the summation of contrast over area is spatially extensive (occurring over 33 stimulus carrier cycles), and that summation behaviour is the same in the fovea, parafovea, and periphery. Summation occurs according to a fourth-root summation rule, consistent with a “noisy energy” model. This work is extended to investigate the visual deficit in amblyopia, finding that area summation is normal in amblyopic observers. Finally, the methods used to study the summation of threshold contrast over area are adapted to investigate the integration of coherent orientation signals in a texture. The results of this study are described by a two-stage model, with a mandatory local combination stage followed by flexible global pooling of these local outputs. In each study, the results suggest a more extensive combination of signals in vision than has been previously understood.