Factors associated with stereopsis and a good visual acuity outcome among children in the Infant Aphakia Treatment Study.

PurposeTo identify factors associated with stereopsis in children with good visual acuity after unilateral congenital cataract surgery in the Infant Aphakia Treatment Study.Patients and methodsInfants with a unilateral congenital cataract (n=114) were randomized to IOL implantation or contact lens correction after cataract surgery. At age 4.5 years, a masked examiner assessed HOTV acuity and stereopsis. Adherence to patching was assessed using 48-h recall telephone interviews and 7-day diaries throughout the first 5 years of life. Ocular motility was evaluated at age 5 years. Baseline, postoperative, and adherence findings were compared between patients with 20/40 or better acuity in their treated eyes with or without stereopsis.ResultsThirty (27%) of 112 patients who were evaluated at age 4.5 years had 20/40 or better acuity in their treated eye. Stereopsis was present on one or more tests in 15 of these 30 (50%) children. Baseline characteristics and postoperative findings did not differ between patients with or without stereopsis. Children with stereopsis were more likely to be orthotropic at distance (P=0.003) and were patched for fewer hours per day throughout the first 5 years of life and the difference increased over time (P<0.001). On average children with stereopsis were patched for 3.4 h/day during the first year of life and patching steadily decreased to 1.8 h/day by age 4 years.ConclusionAmong children with good vision following unilateral congenital cataract surgery, orthophoria and fewer hours of patching, particularly during years 2, 3, and 4, are associated with some evidence of stereopsis.

Effect of carotenoid supplementation on plasma carotenoids, inflammation and visual development in preterm infants.

OBJECTIVE: Dietary carotenoids (lutein, lycopene and ß-carotene) may be important in preventing or ameliorating prematurity complications. Little is known about carotenoid status or effects of supplementation. STUDY DESIGN: This randomized controlled multicenter trial compared plasma carotenoid levels among preterm infants (n=203, <33 weeks gestational age) fed diets with and without added lutein, lycopene and ß-carotene with human milk (HM)-fed term infants. We assessed safety and health. RESULT: Plasma carotenoid levels were higher in the supplemented group at all time points (P<0.0001) and were similar to those of term HM-fed infants. Supplemented infants had lower plasma C-reactive protein (P<0.001). Plasma lutein levels correlated with the full field electroretinogram-saturated response amplitude in rod photoreceptors (r=0.361, P=0.05). The supplemented group also showed greater rod photoreceptor sensitivity (least squares means 6.1 vs 4.1; P<0.05). CONCLUSION: Carotenoid supplementation for preterm infants raises plasma concentrations to those observed in HM-fed term infants. Carotenoid supplementation may decrease inflammation. Our results point to protective effects of lutein on preterm retina health and maturation.

Growth and development in preterm infants fed long-chain polyunsaturated fatty acids: a prospective, randomized controlled trial.

OBJECTIVES: A randomized, masked, controlled trial was conducted to assess effects of supplementing premature infant formulas with oils containing the long-chain polyunsaturated fatty acids, arachidonic acid (AA; 20:4 n6), and docosahexaenoic acid (DHA; 22:6 n3) on growth, visual acuity, and multiple indices of development. METHODS: Infants (N = 470) with birth weights 750 to 1800 g were assigned within 72 hours of the first enteral feeding to 1 of 3 formula groups with or without long-chain polyunsaturated fatty acids: 1) control (N = 144), 2) AA+DHA from fish/fungal oil (N = 140), and 3) AA+DHA from egg-derived triglyceride (egg-TG)/fish oil (N = 143). Infants were fed human milk and/or Similac Special Care with or without 0.42% AA and 0.26% DHA to term corrected age (CA), then fed human milk or NeoSure with or without 0.42% AA and 0.16% DHA to 12 months' CA. Infants fed exclusively human milk to term CA (EHM-T; N = 43) served as a reference. RESULTS: Visual acuity measured by acuity cards at 2, 4, and 6 months' CA was not different among groups. Visual acuity measured by swept-parameter visual-evoked potentials in a subgroup from 3 sites (45 control, 50 AA+DHA [fish/fungal]; 39 AA+DHA [egg-TG/fish]; and 23 EHM-T) was better in both the AA+DHA (fish/fungal; least square [LS] means [cycle/degree] +/- standard error [SE; octaves] 11.4 +/- 0.1) and AA+DHA (egg-TG/fish; 12.5 +/- 0.1) than control (8.4 +/- 0.1) and closer to that of the EHM-T group (16.0 +/- 0.2) at 6 months' CA. Visual acuity improved from 4 to 6 months' CA in all but the control group. Scores on the Fagan test of novelty preference were greater in AA+DHA (egg-TG/fish; LS means +/- SE, 59.4 +/- 7.7) than AA+DHA (fish/fungal; 57.0 +/- 7.5) and control (57.5 +/- 7.4) at 6 months' CA, but not at 9 months' CA. There were no differences in the Bayley Mental Development Index at 12 months' CA. However, the Bayley motor development index was higher for AA+DHA (fish/fungal; LS means +/- SE, 90.6 +/- 4.4) than control (81.8 +/- 4.3) for infants

An electrophysiological technique for assessment of the development of spatial vision.

An objective visual evoked potential (VEP) technique was developed to evaluate spatial processing in humans over a wide range of ages. The constellation of stimulus conditions and analysis methods constitute a novel tool for the assessment of neural development. The key points that delineate this VEP technique are: (1) A brief, 6-s, swept-parameter stimulus with spatial frequency of square-wave grating patterns varied in octave steps, which facilitates correct accommodation and increases the likelihood of collecting uninterrupted, useable data; (2) data collection synchronous with stimulus presentation, which prevents contamination of the relevant frequency component from other frequency components in the response, thereby increasing the signal-to-noise ratio; (3) noise estimation at the response frequency of interest (second harmonic), based on a multivariate statistic (Tcirc2), which yields a realistic measure of signal-to-noise; (4) estimation of grating acuity from linear interpolation of the signal-to-noise measure; (5) monocular testing followed by multivariate statistical comparison of fellow eye data for each spatial frequency condition, which enables the determination of asymmetries within monocular neural pathways; (6) evaluation of maturation of the visual system based on vector-averaged amplitude and phase measures. Preliminary results indicate that reliable response functions are obtained from infants, children, and adults. Acuity estimates increased as a function of age. Phase values decreased consistently with increases in spatial frequency greater than 4 c/deg. Infants produced larger peak amplitude responses than did older observers, consistent with known developmental changes in cortical synaptic density. Phase data for the 2 c/deg condition provided additional evidence for the lack of maturity in the infant visual system as compared with that of older observers.

Visual acuity, erythrocyte fatty acid composition, and growth in term infants fed formulas with long chain polyunsaturated fatty acids for one year. Ross Pediatric Lipid Study.

The CNS and the retina are enriched in long chain polyunsaturated (LCP) fatty acids, specifically docosahexaenoic acid (DHA, 22:6n-3) and arachidonic acid (AA, 20:4n-6), which are present in human milk but not in most infant formulas. In the present study of 134 formula-fed and 63 breast-fed infants, we prospectively evaluated whether providing a source of DHA and AA or DHA alone in formula would increase red blood cell (RBC) phospholipid levels of these fatty acids, enhance visual function, or affect growth during the first year. Healthy term infants < 7 d old were randomized to be fed formulas containing linoleic acid (approximately 10% kcal) and alpha-linolenic acid (approximately 1% kcal) plus (1) no added LCP fatty acids (control formula), (2) DHA (0.12 wt% fatty acids) and AA (0.43 wt%) from egg yolk phospholipid (AA + DHA formula), or (3) DHA (0.2 wt%) from fish oil (DHA formula). A breast-fed group was studied concurrently and permitted formula supplementation after 3 mo. Visual acuity was measured using both the acuity card procedure and a visual evoked potential method at 2, 4, 6, 9, and 12 mo. Infants fed the control formula had 10-40% lower RBC levels of DHA and AA than infants in the breast-fed group. Infants fed the AA + DHA formula had levels of both LCP within approximately 10% of the values for infants in the breast-fed group, and infants fed the DHA formula had 25-55% higher DHA levels and 15-40% lower AA levels. There were no differences in growth or in visual function during this 12-mo feeding study.

Infant visual development: an overview of studies using visual evoked potential measures from Harter to the present.

Studies of sensory and perceptual abilities in infants require creative, innovative techniques. Although the young infant's response repertoire may appear limited to the naive individual, a number of highly refined procedures have been developed and implemented with these non-verbal humans over the last twenty years. The most successful protocols for evaluating visual development rely either on behavioral responses or on electrophysiological recordings. The first published report using visual evoked potentials to study the development of pattern vision in human infants was presented by M. Russell Harter. This work provided the impetus for a wealth of studies exploring issues of visual information processing abilities in early infancy. The available range of data and experimental techniques are now sufficiently refined that many clinical issues are currently being addressed. The purpose of this review is to document the evolution of scientific studies since Harter's seminal work. The selection of protocols presented focuses on those with either current clinical applications or those which hold promise for future applications in the evaluation and treatment issues of abnormal visual development.

Quantification of monocular optokinetic nystagmus asymmetries and motion perception with motion-nulling techniques.

When tested monocularly, strabismic and amblyopic subjects often show asymmetries of optokinetic nystagmus (OKN), with OKN being more readily elicited by temporal-to-nasal than by nasal-to-temporal stimulus motion. We tested five visually normal subjects and ten strabismic and/or amblyopic subjects by use of motion-nulling stimuli, which consisted of superimposed temporal-to-nasal and nasal-to-temporal sinusoidal-grating components with a summed contrast of 100%. Both the direction of OKN and the subject's perceived direction of motion (PDM) were tested. Most normal subjects showed symmetrical OKN and PDM, but a rightward OKN bias was observed in one of the visually normal subjects. Temporal-to-nasal eye-movement biases were seen in most strabismic and amblyopic subjects, whereas PDM biases were smaller and less frequent. The primary purpose of this study was to demonstrate the feasibility of quantifying OKN and PDM asymmetries in a diverse group of visually abnormal adults by use of the motion-nulling technique. Application of this technique to larger and more homogeneous clinical populations may contribute to the continued differentiation and characterization of variants of the visual disorders associated with strabismus and amblyopia and with other defects of binocular vision.

Temporal contrast sensitivity in human infants.

Temporal contrast sensitivity was measured in 1.5- and 3-month-old infants using the FPL procedure. Stimuli were 0.1 c/deg counterphase-flickering sinewave gratings. Temporal rates ranged from 1 to 20 Hz. Because the spatial sinewave underwent phase shifts of 180 degrees, the target could not be seen unless the observer was able to resolve it temporally. Adults were tested with the same temporal stimuli using a 2-alternative forced-choice procedure and a spatial frequency of 0.5 c/deg. Adult temporal CSFs were bandpass with peak sensitivity at 10 Hz. Infant temporal CSFs were lowpass at 1.5 months and bandpass at 3 months. The infants' contrast sensitivity was over a log-unit lower than adults'. Unlike spatial CSFs, infant sensitivity was closest to adult sensitivity at the highest flicker rate.

The acuity card procedure: longitudinal assessments.

Traditional methods of visual assessment in preverbal pediatric patients rely on refined but subjective measurement techniques. A standard ophthalmologic examination includes evaluation of a child's fixation patterns, with performance ranked on the basis of ability to fix and follow an object (F & F) or maintain central, steady fixation (CSM). In the hands of a skilled clinician, these evaluations are important for diagnosis and treatment. Documentation of quantitative changes in visual abilities of preverbal patients, however, has only recently become feasible. We began using the acuity card procedure in our pediatric clinical practice more than 3 years ago. This assessment, a modified version of the standard Forced-Choice Preferential Looking paradigm (FPL), provides quantitative evaluation of visual functioning in preverbal patients. The total number of patients assessed on one or more occasions exceeds 900. Of this group, we followed 83 patients with at least four acuity card evaluations on separate visits. Thirty of these patients, all with different diseases, have been evaluated with acuity cards on six or more visits. We found the information provided by the acuity card assessments extremely helpful in quantifying the developmental and therapeutic changes in vision, previously monitored only qualitatively.

Visual acuity estimates in noncommunicative elderly persons.

The acuity card procedure has been shown to provide reliable grating acuity estimates in pediatric patients. The current study was conducted to determine the usefulness of this procedure in another group of persons in whom conventional acuity measurements are not possible, ie, nursing home residents who suffer from dementing disorders. Binocular visual acuity estimates were obtained in 13 cognitively impaired nursing home residents. Test sessions took 20-30 min each. Both test-retest agreement and inter-observer agreement of Teller Acuity Card (TAC) acuity estimates were good (within 0.5 octave for all residents), demonstrating that this procedure yields reasonable acuity estimates in noncommunicative nursing home residents. The authors stress the potential of this tool for nursing home administrators as well as for researchers.

Electrophysiologic testing techniques for children.

This practical article for clinical electrophysiologists discusses the evaluation of infant and child patients' visual systems using electroretinographic (ERG), electrooculographic (EOG), and visually evoked potential (VEP) techniques. These techniques not only help to secure specific diagnoses, but by systematic assessment of function along the visual pathways can also localize dysfunction underlying visual deficits of pediatric patients. Among children, development as well as disease can affect electrophysiological parameters. Therefore diagnosis of normal or abnormal depends critically on an adequate description of normal responses for age. Procedures that the authors have found feasible, reliable, and valid are summarized. Standardization of pediatric testing appears to be an important next step. The power of ERG, EOG and VEP recordings to demonstrate the neurophysiological basis for pediatric visual impairment is predicted to stimulate further research in this area.

Teller acuity cards versus clinical judgment in the diagnosis of amblyopia with strabismus.

Teller acuity card testing, which is a form of the preferential-looking procedure, is a popular way of assessing visual acuity in preverbal patients. The authors suspected that the clinical judgment of a pediatric ophthalmologist is superior to the Teller acuity cards in diagnosing amblyopia when strabismus is present. Acuity card and fixation preference measurements on each eye were compared at the same clinical visit in a group of 108 strabismic patients. The authors found that the acuity cards could be used to detect amblyopia. However, the pediatric ophthalmologist was more sensitive in diagnosing amblyopia than the Teller acuity cards in the presence of strabismus.

The development of basic mechanisms of pattern vision: spatial frequency channels.

The mature visual system possesses mechanisms that analyze visual inputs into bands of spatial frequency. This analysis appears to be important to several visual capabilities. We have investigated the development of these spatial-frequency channels in young infants. Experiment 1 used a masking paradigm to test 6-week-olds, 12-week-olds, and adults. The detectability of sine wave gratings of different spatial frequencies was measured in the presence and the absence of a narrowband noise masker. The 12-week data showed that at least two spatial-frequency channels with adultlike specificity are present at 12 weeks. The 6-week data did not reveal the presence of narrowband spatial-frequency channels. Experiment 2 used a different paradigm to investigate the same issue. The detectability of gratings composed of two sine wave components was measured in 6-week-olds and adults. The results were entirely consistent with those of experiment 1. The 12-week and adult data indicated the presence of narrowband spatial-frequency channels. The 6-week data did not. The results of these experiments suggest that the manner in which pattern information is processed changes fundamentally between 6 and 12 weeks of age.

Assessment and prediction of visual acuity in 3- to 4-year-old children born prior to term.

Previous studies of school-age children born prior to term indicate that they often have visual acuity that is slightly poorer than normal. However, visual acuity results for preschool-age preterm children have not been reported. In this study, we used the operant preferential looking procedure to measure the visual acuities of 23 3- to 4-year-old preterm children. The results indicated that, although many of the children had acuities within the normal range, the average acuity of the preterm children was slightly poorer than that of full-term children of the same age, even when children with significant refractive errors were eliminated from the sample. Neither birthweight, gestational age at birth, nor the presence of respiratory distress syndrome during infancy were predictive of later visual acuity. However, preferential looking acuity screening at 4 months corrected age did have some predictive value, in that 3 of the 4 infants who failed to complete testing at 4 months showed poor performance at 3 to 4 years of age.

Infant color vision: the effect of test field size on Rayleigh discriminations.

The capacity of 1- and 3-month-old infants to discriminate 589 nm and 650 nm test fields from a 589 nm surround was tested using the forced-choice preferential looking (FPL) technique. The size of the test field ranged from 1 to 8 degrees. Test field size strongly influenced the infants' performance. One-month-olds discriminated 8 and 4 degrees (but not 2 degrees) 650 nm fields from the 589 nm surround; 3-month-olds discriminated 4 and 2 degrees (but not 1 degree) 650 nm fields from the 589 nm surround. The dependence of performance on field size suggests that infants' discrimination failures with small fields are due to immaturities of spatial processing or postreceptoral chromatic mechanisms, rather than to any absence or anomaly of receptor types. In addition, adult subjects rated the hue, brightness, and salience of the test stimuli at 0, 26, 52, and 78 degrees eccentricity. The analogy often made between infant vision and adult peripheral vision is discussed in relation to these data.

The maturation of vestibular nystagmus in infancy and childhood.

The displacements, durations, and velocities of the slow and fast components of both the primary and secondary nystagmus induced by constant angular acceleration were measured in 46 normal children 1 month to 11 years old. There were significant changes in nystagmus parameters in respect to maturation. The young infant had larger amplitude, higher velocity beats than the older child during both the primary and the secondary nystagmus. Parameters describing both the primary and the secondary nystagmus reached their peak values and terminated earlier in the infant than in the older child. Although the slow component velocity during secondary nystagmus was much slower than during the primary nystagmus at all ages, the secondary nystagmus/primary nystagmus ratio was significantly greater in early infancy. Thus, in infancy, as compared with later childhood, the vigor of the secondary nystagmus was disproportionately greater than the primary nystagmus. These results were discussed in relation to the maturation both of vestibular responsiveness and of vestibular adaptation.