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"Hunter, David G"
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Assessing Binocular Interaction in Amblyopia and Its Clinical Feasibility
To measure binocular interaction in amblyopes using a rapid and patient-friendly computer-based method, and to test the feasibility of the assessment in the clinic.
Binocular interaction was assessed in subjects with strabismic amblyopia (n = 7), anisometropic amblyopia (n = 6), strabismus without amblyopia (n = 15) and normal vision (n = 40). Binocular interaction was measured with a dichoptic phase matching task in which subjects matched the position of a binocular probe to the cyclopean perceived phase of a dichoptic pair of gratings whose contrast ratios were systematically varied. The resulting effective contrast ratio of the weak eye was taken as an indicator of interocular imbalance. Testing was performed in an ophthalmology clinic under 8 mins. We examined the relationships between our binocular interaction measure and standard clinical measures indicating abnormal binocularity such as interocular acuity difference and stereoacuity. The test-retest reliability of the testing method was also evaluated.
Compared to normally-sighted controls, amblyopes exhibited significantly reduced effective contrast (∼20%) of the weak eye, suggesting a higher contrast requirement for the amblyopic eye compared to the fellow eye. We found that the effective contrast ratio of the weak eye covaried with standard clincal measures of binocular vision. Our results showed that there was a high correlation between the 1st and 2nd measurements (r = 0.94, p<0.001) but without any significant bias between the two.
Our findings demonstrate that abnormal binocular interaction can be reliably captured by measuring the effective contrast ratio of the weak eye and quantitative assessment of binocular interaction is a quick and simple test that can be performed in the clinic. We believe that reliable and timely assessment of deficits in a binocular interaction may improve detection and treatment of amblyopia.
Journal Article
Durable recovery from amblyopia with donepezil
An elevated threshold for neuroplasticity limits visual gains with treatment of residual amblyopia in older children and adults. Acetylcholinesterase inhibitors (AChEI) can enable visual neuroplasticity and promote recovery from amblyopia in adult mice. Motivated by these promising findings, we sought to determine whether donepezil, a commercially available AChEI, can enable recovery in older children and adults with residual amblyopia. In this open-label pilot efficacy study, 16 participants (mean age 16 years; range 9–37 years) with residual anisometropic and/or strabismic amblyopia were treated with daily oral donepezil for 12 weeks. Donepezil dosage was started at 2.5 or 5.0 mg based on age and increased by 2.5 mg if the amblyopic eye visual acuity did not improve by 1 line from the visit 4 weeks prior for a maximum dosage of 7.5 or 10 mg. Participants < 18 years of age further patched the dominant eye. The primary outcome was visual acuity in the amblyopic eye at 22 weeks, 10 weeks after treatment was discontinued. Mean amblyopic eye visual acuity improved 1.2 lines (range 0.0–3.0), and 4/16 (25%) improved by ≥ 2 lines after 12 weeks of treatment. Gains were maintained 10 weeks after cessation of donepezil and were similar for children and adults. Adverse events were mild and self-limited. Residual amblyopia improves in older children and adults treated with donepezil, supporting the concept that the critical window of visual cortical plasticity can be pharmacologically manipulated to treat amblyopia. Placebo-controlled studies are needed.
Journal Article
The complete annotated Grateful Dead lyrics : the collected lyrics of Robert Hunter and John Barlow, lyrics to all original songs, with selected traditional and cover songs
A complete collection of annotated lyrics by the prolific rock band, published to coincide with their fiftieth anniversary, features literary, historical, and cultural references for every original song.
Book
Binocular Summation and Suppression of Contrast Sensitivity in Strabismus, Fusion and Amblyopia
: Amblyopia and strabismus affect 2%-5% of the population and cause a broad range of visual deficits. The response to treatment is generally assessed using visual acuity, which is an insensitive measure of visual function and may, therefore, underestimate binocular vision gains in these patients. On the other hand, the contrast sensitivity function (CSF) generally takes longer to assess than visual acuity, but it is better correlated with improvement in a range of visual tasks and, notably, with improvements in binocular vision. The present study aims to assess monocular and binocular CSFs in amblyopia and strabismus patients.
: Both monocular CSFs and the binocular CSF were assessed for subjects with amblyopia (
= 11), strabismus without amblyopia (
= 20), and normally sighted controls (
= 24) using a tablet-based implementation of the quick CSF, which can assess a full CSF in <3 min. Binocular summation was evaluated against a baseline model of simple probability summation.
: The CSF of amblyopic eyes was impaired at mid-to-high spatial frequencies compared to fellow eyes, strabismic eyes without amblyopia, and control eyes. Binocular contrast summation exceeded probability summation in controls, but not in subjects with amblyopia (with or without strabismus) or strabismus without amblyopia who were able to fuse at the test distance. Binocular summation was less than probability summation in strabismic subjects who were unable to fuse.
: We conclude that monocular and binocular contrast sensitivity deficits define important characteristics of amblyopia and strabismus that are not captured by visual acuity alone and can be measured efficiently using the quick CSF.
Journal Article
Decreased scene-selective activity within the posterior intraparietal cortex in amblyopic adults
Amblyopia is a developmental disorder associated with reduced performance in visually guided tasks, including binocular navigation within natural environments. To help understand the underlying neurological disorder, we used fMRI to test the impact of amblyopia on the functional organization of scene-selective cortical areas, including the posterior intraparietal gyrus scene-selective (PIGS) area, a recently discovered region that responds selectively to ego-motion within naturalistic environments.
Nineteen amblyopic adults (10 females) and thirty age-matched controls (15 females) participated in this study. Amblyopic participants spanned a wide range of amblyopia severity, based on their interocular visual acuity difference and stereoacuity. The visual function questionnaire (VFQ-39) was used to assess the participants' perception of their visual capabilities.
Compared to controls, we found weaker scene-selective activity within the PIGS area in amblyopic individuals. By contrast, the level of scene-selective activity across the occipital place area (OPA), parahippocampal place area (PPA), and retrosplenial cortex (RSC) remained comparable between amblyopic and control participants. The participants' scores on \"general vision\" (VFQ-39 subscale) correlated with the level of scene-selective activity in PIGS.
These results provide novel and direct evidence for the impact of amblyopia on scene processing within the human brain, thus enabling future studies to potentially link these changes across the spectrum of documented disabilities in amblyopia.
Journal Article
Alzheimer's Disease Amyloid-β Links Lens and Brain Pathology in Down Syndrome
Down syndrome (DS, trisomy 21) is the most common chromosomal disorder and the leading genetic cause of intellectual disability in humans. In DS, triplication of chromosome 21 invariably includes the APP gene (21q21) encoding the Alzheimer's disease (AD) amyloid precursor protein (APP). Triplication of the APP gene accelerates APP expression leading to cerebral accumulation of APP-derived amyloid-beta peptides (Abeta), early-onset AD neuropathology, and age-dependent cognitive sequelae. The DS phenotype complex also includes distinctive early-onset cerulean cataracts of unknown etiology. Previously, we reported increased Abeta accumulation, co-localizing amyloid pathology, and disease-linked supranuclear cataracts in the ocular lenses of subjects with AD. Here, we investigate the hypothesis that related AD-linked Abeta pathology underlies the distinctive lens phenotype associated with DS. Ophthalmological examinations of DS subjects were correlated with phenotypic, histochemical, and biochemical analyses of lenses obtained from DS, AD, and normal control subjects. Evaluation of DS lenses revealed a characteristic pattern of supranuclear opacification accompanied by accelerated supranuclear Abeta accumulation, co-localizing amyloid pathology, and fiber cell cytoplasmic Abeta aggregates (approximately 5 to 50 nm) identical to the lens pathology identified in AD. Peptide sequencing, immunoblot analysis, and ELISA confirmed the identity and increased accumulation of Abeta in DS lenses. Incubation of synthetic Abeta with human lens protein promoted protein aggregation, amyloid formation, and light scattering that recapitulated the molecular pathology and clinical features observed in DS lenses. These results establish the genetic etiology of the distinctive lens phenotype in DS and identify the molecular origin and pathogenic mechanism by which lens pathology is expressed in this common chromosomal disorder. Moreover, these findings confirm increased Abeta accumulation as a key pathogenic determinant linking lens and brain pathology in both DS and AD.
Journal Article
Strabismus Surgery in Orthophoric Patients with Abduction Limitation
Patients with symptomatic esotropia in lateral gaze after lateral rectus recession may not be offered surgery if they are orthophoric in primary gaze due to concern of creating diplopia in primary gaze. There are currently no reports of the surgical management of these cases. The purpose of this study was to report our experience and describe the surgical outcomes for these rare patients.
A comprehensive, retrospective review of all patients undergoing strabismus surgery at Boston Children's Hospital over an 11-year period identified all cases of orthophoric patients operated on for diplopia in lateral gaze following lateral rectus recession(s). Surgical approach, pre- and post-operative measurements in diagnostic gaze positions, and surgical outcomes were assessed. We developed a new lateral incomitance (LI) score to characterize patient disability before and after surgery. Main outcome measures were improvement in LI score and lateral gaze diplopia, lack of new-onset diplopia in primary gaze, and patient/surgeon satisfaction.
In all cases, previously recessed lateral rectus muscles were advanced 2-3 mm with an adjustable suture technique despite anticipated exotropia in primary gaze. Early, large-angle, transient sequential exotropia with diplopia was common. All patients had resolution of lateral-gaze diplopia with improvement in LI score by 8-18 PD, and none experienced persistent new-onset diplopia in primary gaze (median follow-up 16 months; range, 8.5-83 months). One patient with a history of surgery for convergence insufficiency developed a well-controlled intermittent exotropia; no other patient had exotropia in primary gaze.
Small, adjustable advancements of the lateral rectus muscles provided excellent results in our series of patients with lateral gaze esotropia caused by previous lateral rectus recessions. Despite large, early overcorrections, LI scores improved in all cases, and no patient had recurrence of symptomatic exotropia. The results will support surgical decision-making in the management of these challenging cases.
Journal Article
Drive-by Photoscreening Letter
David G Hunter Boston Children's Hospital, Harvard Medical School, Boston, MA, USACorrespondence: David G Hunter Email david.hunter@childrens.harvard.edu In their article, \"Drive-by Photoscreening,\"1 Keffalos, Martin, and Arnold makeimpressive, hands-on efforts to modify vision screening devices to enable theircontinued use during a pandemic. I would like to offer two clarifications. View the original paper byKeffalos and colleagues
Journal Article