Benjamin Thompson

A new binocular approach to the treatment of amblyopia in adults well beyond the critical period of visual development.

PURPOSE The present treatments for amblyopia are predominantly monocular aiming to improve the vision in the amblyopic eye through either patching of the fellow fixing eye or visual training of the amblyopic eye. This approach is problematic, not least of which because it rarely results in establishment of binocular function. Recently it has shown that amblyopes possess binocular cortical mechanisms for both threshold and suprathreshold stimuli. METHODS We outline a novel procedure for measuring the extent to which the fixing eye suppresses the fellow amblyopic eye, rendering what is a structurally binocular system, functionally monocular. RESULTS Here we show that prolonged periods of viewing (under the artificial conditions of stimuli of different contrast in each eye) during which information from the two eyes is combined leads to a strengthening of binocular vision in strabismic amblyopes and eventual combination of binocular information under natural viewing conditions (stimuli of the same contrast in each eye). Concomitant improvement in monocular acuity of the amblyopic eye occurs with this reduction in suppression and strengthening of binocular fusion. Furthermore, in a majority of patients tested, stereoscopic function is established. CONCLUSIONS This provides the basis for a new treatment of amblyopia, one that is purely binocular and aimed at reducing suppression as a first step.

Dichoptic training enables the adult amblyopic brain to learn

Adults with amblyopia, a common visual cortex disorder caused primarily by binocular disruption during an early critical period, do not respond to conventional therapy involving occlusion of one eye. But it is now clear that the adult human visual cortex has a significant degree of plasticity, suggesting that something must be actively preventing the adult brain from learning to see through the amblyopic eye. One possibility is an inhibitory signal from the contralateral eye that suppresses cortical inputs from the amblyopic eye. Such a gating mechanism could explain the apparent lack of plasticity within the adult amblyopic visual cortex. Here we provide direct evidence that alleviating suppression of the amblyopic eye through dichoptic stimulus presentation induces greater levels of plasticity than forced use of the amblyopic eye alone. This indicates that suppression is a key gating mechanism that prevents the amblyopic brain from learning to see.

Measurement of suprathreshold binocular interactions in amblyopia

It has been established that in amblyopia, information from the amblyopic eye (AME) is not combined with that from the fellow fixing eye (FFE) under conditions of binocular viewing. However, recent evidence suggests that mechanisms that combine information between the eyes are intact in amblyopia. The lack of binocular function is most likely due to the imbalanced inputs from the two eyes under binocular conditions [Baker, D. H., Meese, T. S., Mansouri, B., & Hess, R. F. (2007b). Binocular summation of contrast remains intact in strabismic amblyopia. Investigative Ophthalmology & Visual Science, 48(11), 5332-5338]. We have measured the extent to which the information presented to each eye needs to differ for binocular combination to occur and in doing so we quantify the influence of interocular suppression. We quantify these suppressive effects for suprathreshold processing of global stimuli for both motion and spatial tasks. The results confirm the general importance of these suppressive effects in rendering the structurally binocular visual system of a strabismic amblyope, functionally monocular.

A binocular approach to treating amblyopia: antisuppression therapy.

Purpose. We developed a binocular treatment for amblyopia based on antisuppression therapy. Methods. A novel procedure is outlined for measuring the extent to which the fixing eye suppresses the fellow amblyopic eye. We hypothesize that suppression renders a structurally binocular system, functionally monocular. Results. We demonstrate using three strabismic amblyopes that information can be combined normally between their eyes under viewing conditions where suppression is reduced. Also, we show that prolonged periods of viewing (under the artificial conditions of stimuli of different contrast in each eye) during which information from the two eyes is combined leads to a strengthening of binocular vision in such cases and eventual combination of binocular information under natural viewing conditions (stimuli of the same contrast in each eye). Concomitant improvement in monocular acuity of the amblyopic eye occurs with this reduction in suppression and strengthening of binocular fusion. Furthermore, in each of the three cases, stereoscopic function is established. Conclusions. This provides the basis for a new treatment of amblyopia, one that is purely binocular and aimed at reducing suppression as a first step.

A Game Platform for Treatment of Amblyopia

We have developed a prototype device for take-home use that can be used in the treatment of amblyopia. The therapeutic scenario we envision involves patients first visiting a clinic, where their vision parameters are assessed and suitable parameters are determined for therapy. Patients then proceed with the actual therapeutic treatment on their own, using our device, which consists of an Apple iPod Touch running a specially modified game application. Our rationale for choosing to develop the prototype around a game stems from multiple requirements that such an application satisfies. First, system operation must be sufficiently straight-forward that ease-of-use is not an obstacle. Second, the application itself should be compelling and motivate use more so than a traditional therapeutic task if it is to be used regularly outside of the clinic. This is particularly relevant for children, as compliance is a major issue for current treatments of childhood amblyopia. However, despite the traditional opinion that treatment of amblyopia is only effective in children, our initial results add to the growing body of evidence that improvements in visual function can be achieved in adults with amblyopia.

Brain Plasticity in the Adult: Modulation of Function in Amblyopia with rTMS

Amblyopia is a cortically based visual disorder caused by disruption of vision during a critical early developmental period. It is often thought to be a largely intractable problem in adult patients because of a lack of neuronal plasticity after this critical period [1]; however, recent advances have suggested that plasticity is still present in the adult amblyopic visual cortex [2-6]. Here, we present data showing that repetitive transcranial magnetic stimulation (rTMS) of the visual cortex can temporarily improve contrast sensitivity in the amblyopic visual cortex. The results indicate continued plasticity of the amblyopic visual system in adulthood and open the way for a potential new therapeutic approach to the treatment of amblyopia.

Deficient responses from the lateral geniculate nucleus in humans with amblyopia

Amblyopia or lazy eye is the most common cause of uniocular blindness in adults. It is caused by a disruption to normal visual development as a consequence of unmatched inputs from the two eyes in early life, arising from a turned eye (strabismus), unequal refractive error (anisometropia) or form deprivation (e.g. cataract). Animal models based on extracellular recordings in anesthetized animals suggest that the earliest site of the anomaly in the primate visual pathway is the primary visual cortex (corresponding to the striate cortex, cytoarchitectonic area 17 and area V1), which is where inputs from the two eyes are first combined in an excitatory fashion, whereas more distal and monocular processing structures such as the retina and lateral geniculate nucleus (LGN) are normal. Using high‐field functional magnetic resonance imaging in a group of human adults with amblyopia, we demonstrate that functional deficits are first observable at a thalamic level, that of the LGN. Our results suggest the need to re‐evaluate the current models of amblyopia that are based on the assumption of a purely cortical dysfunction, as well as the role for the LGN in visual development.

The Role of Suppression in Amblyopia

PURPOSE This study had three main goals: to assess the degree of suppression in patients with strabismic, anisometropic, and mixed amblyopia; to establish the relationship between suppression and the degree of amblyopia; and to compare the degree of suppression across the clinical subgroups within the sample. METHODS Using both standard measures of suppression (Bagolini lenses and neutral density [ND] filters, Worth 4-Dot test) and a new approach involving the measurement of dichoptic motion thresholds under conditions of variable interocular contrast, the degree of suppression in 43 amblyopic patients with strabismus, anisometropia, or a combination of both was quantified. RESULTS There was good agreement between the quantitative measures of suppression made with the new dichoptic motion threshold technique and measurements made with standard clinical techniques (Bagolini lenses and ND filters, Worth 4-Dot test). The degree of suppression was found to correlate directly with the degree of amblyopia within our clinical sample, whereby stronger suppression was associated with a greater difference in interocular acuity and poorer stereoacuity. Suppression was not related to the type or angle of strabismus when this was present or the previous treatment history. CONCLUSIONS These results suggest that suppression may have a primary role in the amblyopia syndrome and therefore have implications for the treatment of amblyopia.

Neonatal Glycemia and Neurodevelopmental Outcomes at 2 Years

BACKGROUND Neonatal hypoglycemia is common and can cause neurologic impairment, but evidence supporting thresholds for intervention is limited. METHODS We performed a prospective cohort study involving 528 neonates with a gestational age of at least 35 weeks who were considered to be at risk for hypoglycemia; all were treated to maintain a blood glucose concentration of at least 47 mg per deciliter (2.6 mmol per liter). We intermittently measured blood glucose for up to 7 days. We continuously monitored interstitial glucose concentrations, which were masked to clinical staff. Assessment at 2 years included Bayley Scales of Infant Development III and tests of executive and visual function. RESULTS Of 614 children, 528 were eligible, and 404 (77% of eligible children) were assessed; 216 children (53%) had neonatal hypoglycemia (blood glucose concentration, <47 mg per deciliter). Hypoglycemia, when treated to maintain a blood glucose concentration of at least 47 mg per deciliter, was not associated with an increased risk of the primary outcomes of neurosensory impairment (risk ratio, 0.95; 95% confidence interval [CI], 0.75 to 1.20; P=0.67) and processing difficulty, defined as an executive-function score or motion coherence threshold that was more than 1.5 SD from the mean (risk ratio, 0.92; 95% CI, 0.56 to 1.51; P=0.74). Risks were not increased among children with unrecognized hypoglycemia (a low interstitial glucose concentration only). The lowest blood glucose concentration, number of hypoglycemic episodes and events, and negative interstitial increment (area above the interstitial glucose concentration curve and below 47 mg per deciliter) also did not predict the outcome. CONCLUSIONS In this cohort, neonatal hypoglycemia was not associated with an adverse neurologic outcome when treatment was provided to maintain a blood glucose concentration of at least 47 mg per deciliter. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and others.).

Restoration of Binocular Vision in Amblyopia

Purpose: To develop a treatment for amblyopia based on re-establishing binocular vision. Methods: A novel procedure is outlined for measuring and reducing the extent to which the fixing eye suppresses the fellow amblyopic eye in adults with amblyopia. We hypothesize that suppression renders a structurally binocular system, functionally monocular. Results: We demonstrate that strabismic amblyopes can combine information normally between their eyes under viewing conditions where suppression is reduced by presenting stimuli of different contrast to each eye. Furthermore we show that prolonged periods of binocular combination leads to a strengthening of binocular vision in strabismic amblyopes and eventual combination of binocular information under natural viewing conditions (stimuli of the same contrast in each eye). Concomitant improvement in monocular acuity of the amblyopic eye occurs with this reduction in suppression and strengthening of binocular fusion. Additionally, stereoscopic function was established in the majority of patients tested. We have implemented this approach on a headmounted device as well as on a handheld iPod. Conclusion: This provides the basis for a new treatment of amblyopia, one that is purely binocular and aimed at reducing suppression as a first step.