Krista R. Kelly

Amblyopic children read more slowly than controls under natural, binocular reading conditions

BACKGROUND Recent evidence suggests that amblyopia results in fixation instability and atypical saccades. Reading is a vision-reliant ability that requires sequential eye movements, including forward and regressive saccades. This study investigated reading and associated eye movements in school-age amblyopic children. METHODS Amblyopic children with strabismus and/or anisometropia (n = 29) were compared to nonamblyopic children treated for strabismus (n = 23) and normal control children (n = 21). While fitted with the ReadAlyzer, an eye movement recording system, children silently read a grade-level paragraph of text during binocular viewing. Reading rate, number of forward and regressive saccades per 100 words, and fixation duration were determined. Comprehension was evaluated with a 10-item quiz; only data from children with at least 80% correct responses were included. RESULTS Amblyopic children read more slowly and had more saccades compared with nonamblyopic children with treated strabismus and normal controls. Fixation duration did not differ significantly for amblyopic children versus normal controls. Treated strabismic children without amblyopia did not differ significantly from normal controls on any reading measure. Amblyopic eye visual acuity was not correlated with any reading measure. CONCLUSIONS Amblyopia was associated with slower reading speed in school-age children. Treatment for monocular amblyopia visual acuity impairment could improve reading speed and efficiency.

Binocular iPad Game vs Patching for Treatment of Amblyopia in Children: A Randomized Clinical Trial

Importance Fellow eye patching has long been the standard treatment for amblyopia, but it does not always restore 20/20 vision or teach the eyes to work together. Amblyopia can be treated with binocular games that rebalance contrast between the eyes so that a child may overcome suppression. However, it is unclear whether binocular treatment is comparable to patching in treating amblyopia. Objectives To assess the effectiveness of a binocular iPad (Apple Inc) adventure game as amblyopia treatment and compare this binocular treatment with patching, the current standard of care. Design, Setting, and Participants This investigation was a randomized clinical trial with a crossover design at a nonprofit eye research institute. Between February 20, 2015, and January 4, 2016, a total of 28 patients were enrolled in the study, with 14 randomized to binocular game treatment and 14 to patching treatment. Interventions Binocular game and patching as amblyopia treatments. Main Outcomes and Measures The primary outcome was change in amblyopic eye best-corrected visual acuity (BCVA) at the 2-week visit. Secondary outcomes were change in stereoacuity and suppression at the 2-week visit and change in BCVA at the 4-week visit. Results Among 28 children, the mean (SD) age at baseline was 6.7 (1.4) years (age range, 4.6-9.5 years), and 7 (25%) were female. At baseline, the mean (SD) amblyopic eye BCVA was 0.48 (0.14) logMAR (approximately 20/63; range, 0.3-0.8 logMAR [20/40 to 20/125]), with 14 children randomized to the binocular game and 14 to patching for 2 weeks. At the 2-week visit, improvement in amblyopic eye BCVA was greater with the binocular game compared with patching, with a mean (SD) improvement of 0.15 (0.08) logMAR (mean [SD], 1.5 [0.8] lines) vs 0.07 (0.08) logMAR (mean [SD], 0.7 [0.8] line; P = .02) after 2 weeks of treatment. These improvements from baseline were significant for the binocular game (mean [SD] improvement, 1.5 [0.8] lines; P < .001) and for patching (mean [SD] improvement, 0.7 [0.8] line; P = .006). Depth of suppression improved from baseline at the 2-week visit for the binocular game (mean [SD], 4.82 [2.82] vs 3.24 [2.87]; P = .03) and for patching (mean [SD], 4.77 [3.10] vs 2.57 [1.67]; P = .004). Patching children crossed over to binocular game treatment, and all 28 children played the game for another 2 weeks. At the 4-week visit, no group difference was found in BCVA change, with children who crossed over to the binocular games catching up with children treated with binocular games, for a mean (SD) improvement of 0.17 (0.10) logMAR (mean [SD], 1.7 [1.0] lines) for the binocular game vs a mean (SD) improvement of 0.16 (0.12) logMAR (mean [SD], 1.6 [1.2] lines) for the patching crossover (P = .73). Conclusions and Relevance A binocular iPad game was effective in treating childhood amblyopia and was more efficacious than patching at the 2-week visit. Binocular games that rebalance contrast to overcome suppression are a promising additional option for treating amblyopia. Trial Registration clinicaltrials.gov Identifier: NCT02365090.

Impaired face processing in early monocular deprivation from enucleation.

Purpose. We investigated the effects of early monocular enucleation (ME) (surgical removal of one eye) on a high-level spatial visual ability, namely face perception. Early monocular deprivation of pattern vision from disorders such as strabismus, amblyopia, or cataract is associated with impairments in low-level spatial vision. This is inconsistent with studies of early ME that show either equivalent or enhanced low-level spatial vision compared with controls. Impairments on some aspects of face perception (i.e., feature-spacing and holistic face processing, both of which mature later in life) have been found with early pattern deprivation from congenital cataract. It is not clear whether the intact low-level spatial vision with ME will also persist with high-level face perception or whether deficits similar to those found with cataract will emerge. Methods. We tested individuals who have experienced early ME and controls on a series of high-level spatial visual tasks that measure feature-spacing, feature, and holistic face processing. Results. The ME group were slower for feature spacing and feature tasks. Furthermore, the ME group did not exhibit the normal pattern of poorer performance on the aligned compared with misaligned composite face discrimination tasks, demonstrating a lack of the composite face effect. However, they did show the normal pattern of poorer performance on same vs. different trials on the aligned tasks. Conclusions. These results indicate an impairment in the feature spacing and feature aspects of face perception with ME. They also suggest a present yet, incomplete, development of holistic face processing in this group. Although the complete removal of inhibitory binocular interactions and/or the absence of binocular competition in early ME may result in cortical reorganization of the visual system and preserve low- to mid-level spatial vision, it may be insufficient for the maturation of high-level face perception.

Altered anterior visual system development following early monocular enucleation

Purpose Retinoblastoma is a rare eye cancer that generally occurs before 5 years of age and often results in enucleation (surgical removal) of the cancerous eye. In the present study, we sought to determine the consequences of early monocular enucleation on the morphological development of the anterior visual pathway including the optic chiasm and lateral geniculate nucleus. Methods A group of adults who had one eye enucleated early in life due to retinoblastoma was compared to binocularly intact controls. Although structural changes have previously been reported in late enucleation, we also collected data from one late enucleated participant to compare to our early enucleated participants. Measurements of the optic nerves, optic chiasm, optic tracts and lateral geniculate nuclei were evaluated from T1 weighted and proton density weighted images collected from each participant. Results The early monocular enucleation group exhibited overall degeneration of the anterior visual system compared to controls. Surprisingly, however, optic tract diameter and geniculate volume decreases were less severe contralateral to the remaining eye. Consistent with previous research, the late enucleated participant showed no asymmetry and significantly larger volume decreases in both geniculate nuclei compared to controls. Conclusions The novel finding of an asymmetry in morphology of the anterior visual system following long-term survival from early monocular enucleation indicates altered postnatal visual development. Possible mechanisms behind this altered development include recruitment of deafferented cells by crossing nasal fibres and/or geniculate cell retention via feedback from primary visual cortex. These data highlight the importance of balanced binocular input during postnatal maturation for typical anterior visual system morphology.

Assessing Suppression in Amblyopic Children With a Dichoptic Eye Chart

Purpose Suppression has a key role in the etiology of amblyopia, and contrast-balanced binocular treatment can overcome suppression and improve visual acuity. Quantitative assessment of suppression could have a role in managing amblyopia. We describe a novel eye chart to assess suppression in children. Methods We enrolled 100 children (7–12 years; 63 amblyopic, 25 nonamblyopic with strabismus or anisometropia, 12 controls) in the primary cohort and 22 children (3–6 years; 13 amblyopic, 9 nonamblyopic) in a secondary cohort. Letters were presented on a dichoptic display (5 letters per line). Children wore polarized glasses so that each eye saw a different letter chart. At each position, the identity of the letter and its contrast on each eyes chart differed. Children read 8 lines of letters for each of 3 letter sizes. The contrast balance ratio was the ratio at which 50% of letters seen by the amblyopic eye were reported. Results Amblyopic children had significantly higher contrast balance ratios for all letter sizes compared to nonamblyopic children and controls, requiring 4.6 to 5.6 times more contrast in the amblyopic eye compared to the fellow eye (P < 0.0001). Amblyopic eye visual acuity was correlated with contrast balance ratio (r ranged from 0.49–0.57 for the 3 letter sizes). Change in visual acuity with amblyopia treatment was correlated with change in contrast balance ratio (r ranged from 0.43–0.62 for the 3 letter sizes). Conclusions Severity of suppression can be monitored as part of a routine clinical exam in the management of amblyopia in children.

Abnormal Lateral Geniculate Nucleus and Optic Chiasm in Human Albinism

Our objective was to measure how the misrouting of retinal ganglion cell (RGC) fibers affects the organization of the optic chiasm and lateral geniculate nuclei (LGN) in human albinism. We compared the chiasmal structures and the LGN in both pigmented controls and patients with albinism by using high‐resolution structural magnetic resonance imaging (MRI). We studied 12 patients with oculocutaneous albinism and 12 age‐matched pigmented controls. Using a 3T MRI scanner, we acquired a T1‐weighted three‐dimensional magnetization‐prepared rapid gradient‐echo (MPRAGE) image of the whole brain, oriented so that the optic nerves, chiasm, and tracts were in the same plane. We acquired multiple proton density‐weighted images centered on the thalamus and midbrain, and averaged them to increase the signal, enabling precise manual tracing of the anatomical boundaries of the LGN. Albinism patients exhibited significantly smaller diameters of the optic nerves, chiasm and tracts, and optic chiasm and LGN volume compared with controls (P < 0.001 for all). The reductions in chiasmal diameters in the albinism compared with the control group can be attributed to the abnormal crossing of optic fibers and the reduction of RGCs in the central retina. The volume of the LGN devoted to the center of the visual field may be reduced in albinism due to fewer RGCs representing the area where the fovea would normally lie. Our data may be clinically useful in addressing how genetic deficits compromise proper structural and functional development in the brain. J. Comp. Neurol. 522:2680–2687, 2014.

Impaired speed perception but intact luminance contrast perception in people with one eye.

PURPOSE It is generally accepted that early visual deprivation from monocular enucleation (ME; the surgical removal of one eye) results in intact spatial vision. Yet, motion perception studies in this population yield inconsistent findings. Here, we investigated speed and luminance contrast perception in a group of ME individuals. METHODS Twelve ME participants (mean age = 24 years; mean age at enucleation = 24 months) and 17 controls (mean age = 25 years) viewing binocularly (BV) and monocularly (MV) completed a series of speed discrimination and luminance contrast detection and discrimination tasks. Stimuli consisted of 0.5 cpd vertical sine wave gratings varying in speed (3.8°/s-24°/s) or luminance contrast (0%-78%). A second set of luminance contrast tasks with 4 cpd gratings teased apart any spatial frequency effects. RESULTS The ME group exhibited elevated speed discrimination thresholds compared with BV (P = 0.001) and MV (P = 0.027) controls, but intact luminance contrast discrimination (P = 0.530). Notably, both ME and MV groups displayed elevated luminance contrast detection thresholds compared with the BV group (Ps ≤ 0.006). However, the ME group exhibited slightly lower thresholds compared with MV controls for all 4 cpd tasks. CONCLUSIONS Our data indicate a disruption in the development of speed perception, but not luminance contrast perception with monocular enucleation. These data highlight the importance of receiving healthy binocular vision during postnatal development for the maturation of cortical regions associated with motion processing.

Congenitally Impaired Disparity Vergence in Children With Infantile Esotropia.

Purpose We examined whether congenital impairment of disparity vergence in infantile esotropia (ET) exists in children with short duration ET (≤3 months) compared with long-duration ET and healthy controls. A short duration of misalignment would allow for a substantial amount of balanced binocular input during the critical period of binocular disparity development. Methods A total of 19 children aged 5 to 12 years and treated for infantile ET with a short (≤3 months; n = 10) or long (≥5 months; n = 9) duration of constant misalignment before alignment were enrolled. A total of 22 healthy control children were enrolled as a comparison group. Eye movements during disparity vergence and accommodative vergence were recorded using an EyeLink 1000 binocular eye tracker. Mean response gain was compared between and within groups to determine the effect of duration of misalignment and viewing condition. Results Compared with controls, children with short (P = 0.002) and long (P < 0.001) duration infantile ET had reduced response gains for disparity vergence, but not for accommodative vergence (P = 0.19). Conclusions Regardless of duration of misalignment, children with infantile ET had reduced disparity vergence, consistent with a congenital impairment of disparity vergence in infantile ET. Although early correction of misalignment increases the likelihood that some level of binocular disparity sensitivity will be present, normal levels may never be achieved.

Increased cortical surface area and gyrification following long-term survival from early monocular enucleation

Purpose Retinoblastoma is typically diagnosed before 5 years of age and is often treated by enucleation (surgical removal) of the cancerous eye. Here, we sought to characterize morphological changes of the cortex following long-term survival from early monocular enucleation. Methods Nine adults with early right-eye enucleation (≤48 months of age) due to retinoblastoma were compared to 18 binocularly intact controls. Surface area, cortical thickness, and gyrification estimates were obtained from T1 weighted images and group differences were examined. Results Early monocular enucleation was associated with increased surface area and/or gyrification in visual (i.e., V1, inferior temporal), auditory (i.e., supramarginal), and multisensory (i.e., superior temporal, inferior parietal, superior parietal) cortices compared with controls. Visual cortex increases were restricted to the right hemisphere contralateral to the remaining eye, consistent with previous subcortical data showing asymmetrical lateral geniculate nucleus volume following early monocular enucleation. Conclusions Altered morphological development of visual, auditory, and multisensory regions occurs subsequent to long-time survival from early eye loss.

Altered white matter structure in the visual system following early monocular enucleation

Partial visual deprivation from early monocular enucleation (the surgical removal of one eye within the first few years of life) results in a number of long‐term morphological adaptations in adult cortical and subcortical visual, auditory, and multisensory brain regions. In this study, we investigated whether early monocular enucleation also results in the altered development of white matter structure. Diffusion tensor imaging and probabilistic tractography were performed to assess potential differences in visual system white matter in adult participants who had undergone early monocular enucleation compared to binocularly intact controls. To examine the microstructural properties of these tracts, mean diffusion parameters including fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) were extracted bilaterally. Asymmetries opposite to those observed in controls were found for FA, MD, and RD in the optic radiations, the projections from primary visual cortex (V1) to the lateral geniculate nucleus (LGN), and the interhemispheric V1 projections of early monocular enucleation participants. Early monocular enucleation was also associated with significantly lower FA bidirectionally in the interhemispheric V1 projections. These differences were consistently greater for the tracts contralateral to the enucleated eye, and are consistent with the asymmetric LGN volumes and optic tract diameters previously demonstrated in this group of participants. Overall, these results indicate that early monocular enucleation has long‐term effects on white matter structure in the visual pathway that results in reduced fiber organization in tracts contralateral to the enucleated eye. Hum Brain Mapp 39:133–144, 2018.