Ruth Hamilton

Ophthalmic, clinical and visual electrophysiological findings in children born to mothers prescribed substitute methadone in pregnancy

Background and aims There are growing concerns regarding visual outcome of infants exposed to opiates (including substitute methadone) and/or benzodiazepines in utero. We describe the combined ophthalmology and visual electrophysiology findings in 20 infants and children who had been exposed to substitute methadone and other drugs of misuse in utero. Methods This was a descriptive case series of 20 patients, all of whom had been referred to a paediatric visual electrophysiology service because of concerns regarding visual function, and all of whom had been exposed to methadone in utero. All children underwent a full ophthalmic and orthoptic examination as well as visual electrophysiology testing deemed appropriate on an individual basis. A review was undertaken of paediatric case notes and of maternal antenatal urine toxicology. Results Ophthalmic abnormalities included reduced acuity (95%), nystagmus (70%), delayed visual maturation (50%), strabismus (30%), refractive errors (30%), and cerebral visual impairment (25%). Visual electrophysiology was abnormal in 60%. A quarter of the children had associated neurodevelopmental abnormalities. The majority of children with nystagmus (79%) had been treated for neonatal abstinence syndrome (NAS). Conclusion Infants born to drug-misusing mothers prescribed methadone in pregnancy are at risk of a range of visual problems, the underlying causes of which are not clear. Those infants with NAS severe enough to receive pharmaceutical treatment may be at particular risk of developing nystagmus. The inclusion of visual electrophysiology in comprehensive visual assessment of children exposed to substance misuse in utero may help clarify the underlying causes by differentiating abnormalities of retinal and cortical origin.

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.

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.

Visual evoked potentials in infants exposed to methadone in utero

We investigated the effects of maternal drug misuse on neonatal visual evoked potentials (VEPs). Flash VEPs were recorded within 4 days of birth from 21 term infants of mothers misusing drugs and prescribed substitute methadone and 20 controls. Waveforms were classified as typical, atypical, immature or non-detectable, and amplitude and latencies were measured. VEPs from drug-exposed infants were less likely to be of typical waveform and more likely to be immature or non-detectable (p<0.01) than those of control infants. They were also smaller in amplitude (median 10.8 vs 24.4 μV, p<0.001). VEPs of drug-exposed infants had matured after 1 week but remained of lower amplitude than VEPs of newborn controls (p<0.01) and were non-detectable in 15%. Flash VEPs differ between maternal drug-exposed and non-drug-exposed newborns. Future research should address the specific effects of maternal methadone and/or other illicit drug misuse on infant VEPs, and associations between neonatal VEPs and subsequent visual development.

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.

Essentials of photometry for clinical electrophysiology of vision

Electrophysiological testing of the visual system requires familiarity with photometry. This technical note outlines the concepts of photometry with a focus on information relevant to clinical ERG and VEP testing. Topics include photometric quantities, consideration of pupil size, specification of brief extended flash stimuli, and the influence of the spectral composition of visual stimuli. Standard units and terms are explained in the context of the ISCEV standards and guidelines for clinical electrophysiology of vision.

Blindsight in children: does it exist and can it be used to help the child? Observations on a case series

Damage to the occipital lobe of the brain results in hemianopia when unilateral, and cerebral blindness when bilateral. However, in some cases a degree of visual function persists in the blind visual field. This aim of this study was to describe this phenomenon of‘blindsight’in a cohort of children with brain‐damage and to relate the clinical features to their visual evoked potentials. We performed a retrospective analysis of 541 case records of children referred to a tertiary vision‐assessment clinic in the Royal Hospital for Sick Children, Glasgow, UK from 1992 to 2002. A total of 541 patients were analyzed (243 females, 298 males; age range 2mo to 19y 6mo, mean 6y 2mo). In 19 children with profound visual impairment and four children with hemianopia (12 females, 11 males; age range 1 to 18y, mean age 8y 3mo), evidence of perception of movement in the blind visual field was found and is described. Flash visual evoked potentials varied from no response to normal and was not correlated with visual behaviour. Recognition, detection, and use of this phenomenon in children is vital to their rehabilitation and interaction with their surroundings.

Contact lens electroretinography in preterm infants from 32 weeks after conception : a development in current methodology

AIM To assess the feasibility of using a contact lens electrode to record the electroretinogram (ERG) in preterm infants less than 35 weeks after conception. METHODS The ERG was recorded from seven very low birthweight preterm infants on a total of 14 occasions using an infant monkey contact lens electrode. Age at recording the first ERG ranged from 23 to 51 days (gestational age 32–34 weeks), and weight ranged upwards from 1100 g. RESULTS No complications were observed. With advancing age and maturity the dark adapted rod threshold decreased, indicating increased retinal sensitivity. CONCLUSIONS Contact lens recording of the ERG from extremely small immature preterm infants is a practicable and well tolerated procedure. This method of recording the ERG will enable further evaluation of retinal development in this vulnerable population.

Erratum to: ISCEV Standard for full-field clinical electroretinography (2015 update)

There is an error in Table 1 of the recently published ISCEV Standard for full-field clinical electroretinography (2015 update) [1]. Users of this standard should note that the filter settings for dark-adapted oscillatory potentials (OPs), as correctly specified in the text, require that the high-pass filter should remove frequencies of 75 Hz and below from the ERG waveform; the low-pass filter setting of 300 Hz or above is the same as for other ERG tests. Table 1 is provided below with the correct bandpass for OPs