Visual outcome in infants born to drug-misusing mothers prescribed methadone in pregnancy.

BACKGROUND: Flash visual evoked potentials (VEPs) were abnormal in a cohort of 100 neonates exposed to maintenance methadone in utero. This prospective cohort study now describes clinical visual and electrophysiological outcomes at 6 months. METHODS: Visual assessment included modified Atkinson test battery; strabismus, nystagmus, reduced visual acuity, delayed visual maturation or refractive error (>3 dioptres) defined a fail. Pattern-onset VEPs were recorded to 120', 60' and 15' checks. RESULTS: 81 drug-exposed and 26 comparison infants (79% and 52% of the original cohorts) were assessed at a median age of 27 weeks (range 26-30). 90% of drug-exposed infants had been additionally exposed to illicit drugs and 41% to excess alcohol in utero. 40% of the drug-exposed cohort failed clinical visual assessment: the relative risk of abnormal assessment was 5.1 (95% CI 1.3 to 20; p=0.02). Nystagmus was particularly common. VEP peak times were slower and amplitudes smaller in drug-exposed infants, of whom 70% had one or more abnormal VEP parameter. Abnormal visual outcome at 6 months was not associated with the pattern of additional drug exposure or a history of neonatal abstinence. CONCLUSIONS: Abnormal visual electrophysiology in infants born to drug-misusing mothers prescribed maintenance methadone persists to 6 months of age, and is associated with abnormal clinical visual assessment.

Neonatal visual evoked potentials in infants born to mothers prescribed methadone.

OBJECTIVE: Drug misuse in pregnancy is associated with impaired infant visual development. Pilot data showed abnormal flash visual evoked potentials (VEPs) in neonates exposed to methadone in utero, but results were confounded by intrauterine growth restriction, gestation, and ongoing drug misuse. This large cohort study aimed to clarify the effects on neonatal flash VEPs of maternal drug misuse in pregnancy, including prescription of substitute methadone and subsequent development of neonatal abstinence syndrome. METHODS: This was a prospective cohort study. Flash VEPs were recorded within 3 days of birth from 100 healthy infants of drug-misusing mothers prescribed substitute methadone during pregnancy and 50 comparison infants matched for birth weight, gestation, and socioeconomic deprivation. VEP morphology was classified as mature, typical, or immature, and amplitudes and implicit times of the major waveform components measured. Drug exposure was determined by maternal history, maternal and infant urine, and meconium toxicology. RESULTS: VEPs from maternal drug-exposed infants were more likely to be of immature waveform (P < .001) and were smaller in overall amplitude (median 27 µV vs 39 µV, P < .001) compared with non-drug-exposed infants. Most infants were exposed to illicit drugs in addition to prescribed methadone; differences in VEP parameters were independently associated with maternal prescribed methadone and persisted after correcting for birth weight, cigarette smoking, and excess in utero alcohol exposure. CONCLUSIONS: In utero exposure to prescribed substitute methadone is associated with altered flash VEPs in the newborn period and these infants may warrant early clinical visual assessment.

Dark-adapted oscillatory potentials in preterm infants with and without retinopathy of prematurity.

PURPOSE: To describe the appearance and maturation of dark-adapted oscillatory potentials (OPs) in electroretinograms (ERGs) recorded from preterm infants, and to determine any effect of retinopathy of prematurity (ROP). METHODS: Dark-adapted ERGs were recorded in conjunction with screening for ROP and at outpatient follow-up, using a flash luminance of 11.3 scot cd s m(-2) (4.06 phot cd s m(-2)). Eligible infants were born before 31 weeks' gestation and/or weighed ≤1,250 grams at birth. RESULTS: Presence or absence of OPs was established for 68 ERG recordings from 38 infants at maturities ranging from 30 weeks' postmenstrual age (PMA) to 28 weeks' post-term corrected age. 20 infants did not develop ROP, eight developed stage 1, one stage 2 and one stage 3 disease which regressed spontaneously. Eight infants received treatment for threshold ROP. OPs were present in 50 % of infants at 36 weeks' PMA and in all by 50 weeks' PMA. The earliest appearance of OPs was at 30+5 weeks' PMA. Individual OP amplitudes increased and peak time of individual OPs decreased with increasing maturity. For infants with threshold ROP summed OP amplitudes tended to be smaller prior to treatment (6.5 vs 9.9µV, P = 0.09) and were significantly smaller by 50 weeks' PMA (14 vs 30µV, P = 0.007). OP1 was less likely to be present in infants who developed stage 3 or worse ROP (P = 0.000). CONCLUSIONS: Dark-adapted OPs are recordable in some preterm infants from 30 weeks' PMA. Relative suppression of early OPs is a potential marker for developing ROP.

Sensitivity and specificity of the step VEP in suspected functional visual acuity loss.

BACKGROUND/AIM: Early and accurate diagnosis of functional visual loss (FVL) allows optimum management. Visual evoked potentials (VEPs) offer a means of objectively estimating acuity and therefore could assist with early and accurate diagnosis. The aim of this study was to assess the sensitivity and specificity of the step VEP in diagnosing FVL. METHODS: A retrospective audit was conducted in 36 school-aged children presenting with reduced visual acuity and clinical suspicion of FVL. All had undergone step VEP testing as part of their investigation. Medical notes were reviewed, and where necessary, referring centres, general practitioners or electronic clinical portals were consulted to obtain longer-term outcome data. RESULTS: Twenty-seven of the 36 patients (75%) were classified as having had FVL: all had a normal step VEP spatial threshold. Nine patients (25 %) had an organic cause for their acuity loss, of whom seven had abnormal step VEP spatial thresholds: the other two patients had some functional overlay to their organic disease. The step VEP sensitivity was 78% (95% confidence interval 40-96%), and specificity was 100% (95% confidence interval 84-100%). CONCLUSION: The high specificity of the step VEP for FVL warrants increased suspicion of an organic cause should the step VEP spatial threshold be abnormal.

Vitamin A supplementation improves retinal function in infants at risk of retinopathy of prematurity.

OBJECTIVE: Preterm infants show reduced retinal sensitivity at term corrected age compared with newborn term infants. We tested the hypothesis that retinal sensitivity in preterm infants is improved by early, high-dose vitamin A. STUDY DESIGN: We report a double-blind, randomized controlled trial of infants <32 weeks' gestation and/or <1501 g birth weight. Supplemented infants received additional intramuscular vitamin A 10 000 IU 3 times weekly from day 2 for a minimum of 2 weeks or until establishment of oral feeding. Hepatic stores were assessed by relative dose response (RDR). The primary outcome measure was cone-corrected dark-adapted retinal rod sensitivity measured by electroretinogram at 36 weeks' postmenstrual age (PMA). RESULTS: Eighty-nine infants (42 supplemented and 47 controls) were recruited. Plasma retinol was higher in supplemented infants at 7 and 28 days (median, 1.0 vs 0.5 µmol/L and 0.7 vs 0.6 µmol/L; P < .001 and .03, respectively). Neither plasma retinol nor RDR differed between groups at 36 weeks' PMA. Retinal sensitivity was greater in supplemented infants (-0.81 vs -0.61 log cd • s • m(-2); P < .03) and was not related to RDR. CONCLUSIONS: Early high-dose intramuscular vitamin A supplementation for infants at risk of retinopathy of prematurity improves retinal function at 36 weeks' PMA.

Maturation of rod function in preterm infants with and without retinopathy of prematurity.

OBJECTIVES: To establish normal development of rod electroretinograms in preterm infants and to assess the effects of retinopathy of prematurity (ROP). STUDY DESIGN: We measured 88 Naka-Rushton functions from 41 preterm infants at maturities from 30 to 72 weeks postmenstrual age (PMA). Outcomes (log sigma, retinal sensitivity and V(max), retinal responsivity) were compared between control (no ROP), untreated ROP, and treated ROP. RESULTS: In control infants, sensitivity increased by 1.5 log units from 30 to 40 weeks PMA and by a further 0.5 log units by 50 weeks PMA but was 0.5 log units less than in similarly-mature, healthy, term-born infants. Average retinal responsivity increased from 23 microV to 90 microV between 30 and 40 weeks PMA and was 35 muV greater at 40 weeks PMA than in similarly-mature term-born infants. At around 36 weeks PMA, (when onset of ROP peaks), infants with untreated ROP had average retinal sensitivity 0.2 log units lower than control infants; sensitivity was reduced further in infants treated for ROP. Retinal responsiveness did not differ between control subjects and untreated infants with ROP but was greatly reduced in infants treated for ROP. CONCLUSIONS: Maturation of rod sensitivity appears to be slowed by preterm birth whereas maturation of rod responsivity is accelerated. ROP reduces retinal sensitivity, and treated ROP reduces both sensitivity and responsivity.

Real-time rapid acuity assessment using VEPs: development and validation of the step VEP technique.

PURPOSE: To develop a reference range of visual acuities corresponding to thresholds found using the step VEP method of rapid, objective visual acuity assessment by using steady state (ss)VEPs in normal adults. METHODS: Sixteen normal adults had visual acuity assessed five times with both the step VEP and with Glasgow Acuity Cards (GAC). Subjects were tested once without filters and with four different levels of optical filtering provided by Bangerter neutral-density filters. Acuity outcomes were compared by linear regression and Bland-Altman analysis. RESULTS: Step VEP and GAC acuities correlated highly (r(2) = 0.60, P = 0.000). GAC scores were predicted with the equation: acuity(GAC) = (0.9 x acuity(step VEP)) - 0.37. Step VEP acuity was 0.46 (95% CI: -0.13 to 1.06) logMAR units greater (poorer) than GAC acuities in these normal subjects. The disparity between test results did not vary with visual acuity. CONCLUSIONS: The step VEP provides a rapid, objective means of estimating visual acuity that can be related to acuity derived from a commonly used letter test.

Ocular biometry in preterm infants: implications for estimation of retinal illuminance.

PURPOSE: Retinal illuminance varies with stimulus luminance, pupil size, eye size, and transmissivity of the ocular media. There are few published data to inform estimates of retinal illuminance in early infancy, and no concurrent studies of pupil size and ocular length have been described. The goals were to document simultaneously the measured ocular parameters in growing preterm infants and to estimate the potential errors associated with using either stimulus luminance or troland value as a proxy for retinal illuminance in this population. METHODS: Ocular biometry including diameters of the eye, vitreous chamber depth (VCD) and dilated pupil diameter was performed on 111 occasions in 33 preterm infants aged between 30 and 55 weeks' postmenstrual age. RESULTS: Eye size increased rapidly between 30 and 55 postmenstrual weeks and was comparable to that of term-born infants. The ratio of dilated pupil area to VCD(2) was highly variable. Retinal illuminance of the infant eye compared with adult eyes was underestimated by both stimulus luminance and troland values. CONCLUSIONS: Stimulus luminance and troland values cannot be used to infer retinal illuminance when comparing eyes of markedly differing sizes or transmissivities. Error in estimating retinal illuminance in prematurely born infants is inevitable because of uncertainty regarding media transmissivity, but this discrepancy can be minimized by using directly measured pupil diameter and data presented herein for eye size in this population.

Development of the electroretinogram between 30 and 50 weeks after conception.

Maturation of the electroretinogram (ERG) reflects retinal development. Serial ERGs recorded from a preterm infant between 30 and 50 weeks after conception showed rapid maturation. A transient loss of retinal sensitivity coincided with clinical signs of stage 2 retinopathy of prematurity (ROP).

Rapid detection of threshold VEPs.

OBJECTIVE: To determine whether a one-dimensional (1D) Laplacian analysis detects steady-state visual evoked potentials (ssVEPs) faster than the standard O(z)-F(z) montage and to establish the optimum position of Laplacian reference electrodes. METHODS: Twenty-two normal adults were shown reversing checks ranging from 1.5' to 60'. Three electrode montages were investigated: O(z)-F(z), LO-F(z) and a 1D Laplacian analysis of 3 occipital electrodes (2O(z)-(RO+LO)). RO and LO were placed symmetrically and horizontally about O(z). Five different locations for RO and LO were investigated. Recordings were analysed in the frequency domain and the presence (and detection time, DT) or absence of a ssVEP defined statistically. Effects of individual, reference electrode site and check size on DT and phase differences between recording montages were investigated. RESULTS: Laplacian analysis detected ssVEPs to small (3') checks faster than O(z)-F(z), by 12.3 and 4.1s on average with Laplacian reference electrodes at 15 and 20% of half-head circumference, respectively. The optimum position of reference electrodes was governed by the instantaneous spatial spread of the response and the noise coherence between midline and lateral electrodes. CONCLUSIONS: A 1D Laplacian analysis can reduce the time to statistical detection of ssVEPs compared to the traditional O(z)-F(z) recording for stimuli near the normal acuity threshold of adults. This in turn could be used to minimise the length of a VEP acuity assessment.

Faster and more sensitive VEP recording in children.

PURPOSE: In the difficult-to-test paediatric population, shorter test procedures are desirable. This study investigates whether Laplacian analysis of a three occipital-electrode montage detects steady-state VEPs (ssVEPs) more often or faster in children than a conventional montage, and if so, in which age groups. METHODS: Steady-state VEPs (7.78 reversals/s; checkerboard stimulus) to various checksizes (60-3', 0.07-14 cpd equivalent) were recorded from 80 normal children aged from 1 month to 13 years and 19 adults. Active occipital electrodes were placed at Oz and symmetrically either side at 15% of the subject's half-head circumference (right occipital and left occipital, RO and LO). The Laplacian analysis used 2Oz-(RO+LO) instead of the conventional Oz-Fz. Fourier analysis and a circular T2 statistic was used to determine VEP detection time (DT). The number of responses detected overall by each analysis method and the effects of age and checksize on DT differences between analysis methods were investigated. RESULTS: The Laplacian analysis detected more VEPs than the conventional Oz-Fz (95 versus 84%, p = 0.001) in children's age groups. The Laplacian analysis also provided faster response detection to 3' checks in all subjects over the age of five, and to 6' and 9' in 7-9-year-olds. CONCLUSION: A Laplacian analysis offers increased sensitivity and faster VEP detection over conventional (Oz-Fz) recording in children over five for threshold-sized VEPs. Simultaneous use of both conventional (Oz-Fz) VEP recording and a Laplacian analysis in all patient ages is likely to give faster, more accurate VEP assessments.