Sarah E. Morale

Cognitive function in 18-month-old term infants of the DIAMOND study: A randomized, controlled clinical trial with multiple dietary levels of docosahexaenoic acid

BACKGROUND Studies investigating cognitive outcomes following docosahexaenoic acid (DHA) supplementation of infant formula yield conflicting results, perhaps due to inadequate dietary concentrations. AIM To determine the optimal DHA concentration in term formula to support cognitive maturation. DESIGN This was a double-masked, randomized, controlled, prospective trial. A total of 181 infants were enrolled at 1-9 days of age and assigned randomly to receive one of four term infant formulas with one of four levels of docosahexaenoic acid: Control (0% DHA), 0.32% DHA, 0.64% DHA, or 0.96% DHA. All DHA-supplemented formulas contained 0.64% arachidonic acid (ARA). Infants were fed the assigned formulas until 12 months of age. One hundred forty-one children completed the 12-month feeding trial and were eligible for this study. Cognitive function was assessed in 131 children at 18 months of age using the Bayley Scales of Infant Development II (BSID II). RESULTS There were no diet group differences on the Mental Development Index (MDI), the Psychomotor Development Index (PDI), or the Behavior Rating Scale (BRS) of the BSID II. However, when the scores of children who received any of the three DHA-supplemented formulas were combined and compared to control children, a significant difference emerged: the MDI scores of DHA-supplemented children were higher (104.1 v. 98.4; p=0.02). CONCLUSIONS These results suggest that dietary supplementation of DHA during the first year of life leads to enhanced cognitive development at 18 months of age. DHA concentration of 0.32% is adequate to improve cognitive function; higher concentrations did not confer additional benefit.

Binocular iPad treatment for amblyopia in preschool children.

BACKGROUND Recent experimental evidence supports a role for binocular visual experience in the treatment of amblyopia. The purpose of this study was to determine whether repeated binocular visual experience with dichoptic iPad games could effectively treat amblyopia in preschool children. METHODS A total of 50 consecutive amblyopic preschool children 3-6.9 years of age were assigned to play sham iPad games (first 5 children) or binocular iPad games (n = 45) for at least 4 hours per week for 4 weeks. Thirty (67%) children in the binocular iPad group and 4 (80%) in the sham iPad group were also treated with patching at a different time of day. Visual acuity and stereoacuity were assessed at baseline, at 4 weeks, and at 3 months after the cessation of game play. RESULTS The sham iPad group had no significant improvement in visual acuity (t4 = 0.34, P = 0.75). In the binocular iPad group, mean visual acuity (plus or minus standard error) improved from 0.43 ± 0.03 at baseline to 0.34 ± 0.03 logMAR at 4 weeks (n = 45; paired t44 = 4.93; P < 0.0001). Stereoacuity did not significantly improve (t44 = 1.35, P = 0.18). Children who played the binocular iPad games for ≥8 hours (≥50% compliance) had significantly more visual acuity improvement than children who played 0-4 hours (t43 = 4.21, P = 0.0001). CONCLUSIONS Repeated binocular experience, provided by dichoptic iPad game play, was more effective than sham iPad game play as a treatment for amblyopia in preschool children.

Three Randomized Controlled Trials of Early Long-Chain Polyunsaturated Fatty Acid Supplementation on Means-End Problem Solving in 9-Month-Olds

This study examines whether feeding infants formula supplemented with long-chain polyunsaturated fatty acids (LCPUFA) improves cognitive function of 9-month-olds. Participants included 229 infants from 3 randomized controlled trials. Children received either formula supplemented with docosahexaenoic acid and arachidonic acid, or a control formula beginning at 1-5 days (12-month feeding study), or following 6 weeks (6-week-weaning study) or 4-6 months of breastfeeding (4-to 6-month weaning study). Infants were assessed with a 2-step problem solving task. In the 12-month feeding and 6-week weaning studies, supplemented children had more intentional solutions (successful task completions) and higher intention scores (goal-directed behaviors) than controls. These results suggest that LCPUFA supplementation improves means-end problem solving.

Dichoptic movie viewing treats childhood amblyopia

BACKGROUND Contrast-balanced dichoptic experience with perceptual-learning tasks or simple games has been shown to improve visual acuity significantly in amblyopia. However, these tasks are intensive and repetitive, and up to 40% of unsupervised patients are noncompliant. We investigated the efficacy of a potentially more engaging movie method to provide contrast-balanced binocular experience via complementary dichoptic stimulation. METHODS Eight amblyopic children 4-10 years of age were enrolled in a prospective cohort study to watch 3 dichoptic movies per week for 2 weeks on a passive 3D display. Dichoptic versions of 18 popular animated feature films were created. A patterned image mask of irregularly shaped blobs was multiplied with the movie images seen by the amblyopic eye and an inverse mask was multiplied with the images seen by the fellow eye. Fellow-eye contrast was initially set at a reduced level that allowed binocular vision and was then incremented by 10% at each visit. Best-corrected visual acuity, random dot stereoacuity, and interocular suppression were measured at baseline and 2 weeks. RESULTS Mean amblyopic eye visual acuity (with standard error of the mean) improved from a logarithm of minimum angle of resolution of 0.72 ± 0.08 at baseline to 0.52 ± 0.09 (P = 0.003); that is, 2.0 lines of improvement at the 2-week outcome visit. No significant change in interocular suppression or stereoacuity was found. CONCLUSIONS Passive viewing of dichoptic feature films is feasible and could be a promising new treatment for childhood amblyopia. The maximum improvement that may be achieved by watching dichoptic movies remains to be determined. No known side effects are associated with this new treatment.

Course of development of global hyperacuity over lifespan.

Purpose. Global visual integration is fundamental to shape and face recognition. Although the maturation of local visual function, such as resolution acuity, has been well documented, less is known about the changes in global visual function during development and with aging. Methods. Two hundred thirty-six normal subjects, ranging in age from 0.25- to 78-years old, participated in the study. Global hyperacuity (detection threshold for radial deformation) was obtained from 300 eyes using either a computerized testing or a chart testing protocol and spatial forced choice (preferential looking for <2.6-year old, pointing for young children, or verbal response for older children and adults). Resolution acuity was also measured. The developmental courses for global hyperacuity and resolution acuity were fit to a 3-segment curve to capture the initial rapid development, followed by a period of stable, adult-level visual function and, finally, the decline in visual function with aging. Results. Curve fitting revealed that global hyperacuity was 0.25 logMAR at 0.25 years of age, and improved rapidly to −0.56 logMAR at 5.4 years of age but did not reach the mean adult level (−0.86 logMAR) until 21 years of age. Global hyperacuity started to deteriorate from 55 years of age at the rate of 0.035 logMAR per decade. In comparison, resolution acuity reached 0.0 logMAR at 5 years of age, and reached the adult level of −0.1 logMAR at 11 years of age. Resolution acuity also started to decrease from 55 years of age at the rate of 0.058 logMAR per decade. Conclusions. Similar to vernier alignment acuity, global hyperacuity improves rapidly during infancy and early childhood but takes longer to reach the adult level than resolution acuity. The delayed maturation of global hyperacuity suggests that further development to refine neural circuitry at the cortical level takes place in the second decade of life.

Binocular iPad treatment of amblyopia for lasting improvement of visual acuity.

Repeated experience with dichoptic perceptual learning tasks and dichoptic game play have been shown to be effective in improving the visual acuity of amblyopic children and adults.1–4 However, whether the visual acuity gains achieved with binocular treatment are long lasting has not yet been addressed. We examined the durability of visual acuity improvements obtained as a result of binocular iPad game play in childhood amblyopia.

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 radial deformation hyperacuity in children with strabismic amblyopia.

PURPOSE 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. METHODS 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. RESULTS 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. CONCLUSIONS 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.

Vernier acuity cards: examination of development and screening validity.

Purpose. Because vernier acuity seems to be limited by the visual cortex, it possesses excellent potential as a clinical/screening tool to detect amblyopia in infants and toddlers. Thus, we developed the vernier acuity cards specifically for this age group. We compared developmental data gathered using this new test and the Teller Acuity Cards. In addition, we compared the clinical/screening validity of the two tests by testing children old enough to complete optotype acuity testing (6.2 ± 2.5 years). Methods. Vernier acuity and grating acuity were assessed in 98 children and 18 adults with normal vision (age range = 2.8 months to 35.8 years). The developmental time course of the two visual functions was compared. In addition, vernier acuity and grating acuity were measured in 43 children with amblyopia and 30 nonamblyopic children with an amblyogenic condition. Each childs grating acuity and vernier acuity were classified as normal/abnormal based on age-appropriate norms. These classifications were compared with amblyopia diagnoses by crowded HOTV or Early Treatment Diabetic Retinopathy Study (ETDRS) testing. Results. Vernier acuity and grating acuity follow different developmental time courses in normal infants and children. Vernier acuity is initially poorer than grating acuity but surpasses it by the age 5 years and is adult-like by the age 8 years. Compared with the Teller Acuity Cards, the vernier acuity cards yielded higher sensitivity (81 vs. 44%) and similar specificity (73 vs. 93%) and were more sensitive to all amblyopia subtypes/levels of severity. Conclusions. The developmental time course of vernier acuity differed from that of grating acuity, implying that it is not mediated by the retina. Also, the impressive validity of the vernier acuity cards suggests that they are an effective tool for detecting amblyopia.

Longitudinal Development of Refractive Error in Children With Accommodative Esotropia: Onset, Amblyopia, and Anisometropia

Purpose We investigated longitudinal changes of refractive error in children with accommodative esotropia (ET) throughout the first 12 years of life, its dependence on age at onset of ET, and whether amblyopia or anisometropia are associated with defective emmetropization. Methods Longitudinal refractive errors in children with accommodative ET were analyzed retrospectively. Eligibility criteria included: initial hyperopia ≥+4.00 diopters (D), initial cycloplegic refraction before 4 years, at least 3 visits, and at least one visit between 7 and 12 years. Children were classified as having infantile (N = 30; onset ≤12 months) or late-onset (N = 78; onset at 18–48 months) accommodative ET. Cycloplegic refractions culled from medical records were converted into spherical equivalent (SEQ). Results Although the initial visit right eye SEQ was similar for the infantile and late-onset groups (+5.86 ± 1.28 and +5.67 ± 1.26 D, respectively), there were different developmental changes in refractive error. Neither group had a significant decrease in hyperopia before age 7 years, but after 7 years, the infantile group experienced a myopic shift of −0.43 D/y. The late-onset group did not experience a myopic shift at 7 to 12 years. Among amblyopic children, a slower myopic shift was observed for the amblyopic eye. Among anisometropic children, the more hyperopic eye experienced more myopic shift than the less hyperopic eye. Conclusions Children with infantile accommodative ET experienced prolonged hyperopia followed by a myopic shift after 7 years of age, consistent with dissociation between infantile emmetropization and school age myopic shift. In contrast, children with late-onset accommodative ET had little myopic shift before or after 7 years.