Dr. Ruth Hamilton: The Present and Future of Electrophysiology Research
ERG technology continues to advance in the ways it can be used to help diagnose and track retinal disease— sometimes, with applications, we didn’t expect. Such as children’s vision affected by maternal opioid use.
We at LKC Technologies are proud to see our technology being used at the frontier of this research.
Here are some relevant studies, authored by Dr. Ruth Hamilton, that have been recently published.
- Hamilton R, 2021: Clinical electrophysiology of vision-commentary on current status and future prospects.
- Mactier H, Hamilton R, 2020: Prenatal opioid exposure - Increasing evidence of harm.
- Monnelly VJ, Hamilton R, Chappell FM, Mactier H, Boardman JP, 2019. Childhood neurodevelopment after prescription of maintenance methadone for opioid dependency in pregnancy: a systematic review and meta-analysis.
- McGlone L, Hamilton R, McCulloch DL, MacKinnon JR, Bradnam M, Mactier H, 2014: Visual outcome in infants born to drug-misusing mothers prescribed methadone in pregnancy.
- McGlone L, Hamilton R, McCulloch DL, Boulton R, Bradnam MS, Weaver LT, Mactier H, 2013: Neonatal visual evoked potentials in infants born to mothers prescribed methadone.
- Mactier H, McGlone L, Hamilton R, MacKinnon JR, 2012: Neonatal abstinence syndrome can be a problem.
- Hamilton R, McGlone L, MacKinnon JR, Russell HC, Bradnam MS, Mactier H, 2010: Ophthalmic, clinical and visual electrophysiological findings in children born to mothers prescribed substitute methadone in pregnancy.
Hamilton R, 2021: Clinical electrophysiology of vision-commentary on current status and future prospects.
Summary:
Visual electrophysiology bridges structural information and clinical observations, providing powerful methods for diagnosing ophthalmic diseases. The objective, quantifiable data provided by electroretinography (ERG) is useful for clinical trials and has been critical in developing key therapies for sight-threatening disease. Early descriptions of clinical methods led to the first published international ERG standard in 1989. The ERG standard has been continually revised and additional standards have been published for consistent testing of specific ophthalmic functions. ERGs from multiple testing centers demonstrate remarkably low variability, meaning that the standards succeed in ensuring comparable readings between different clinics and centers. The ERG standards create comparability and repeatability beyond what is usually achieved in clinical or laboratory measurements, allowing eye care professionals to evaluate a wide array of ophthalmic conditions. As healthcare transforms into data-driven, universal care, ERG should be prioritized for widespread use. Alternative, accessible ERG technology needs to be developed. Quick, easy, robust, widely available ERG tests will bring benefits to large populations of people, including remote and developing communities. Compact systems and handheld devices (such as LKC Technologies’ RETeval) are already paving the way for widespread use of ERG. Further innovations and extensive implementation of ERG is essential to bring these important tests into 21st century healthcare.
Citation and Link:
Hamilton R. Clinical electrophysiology of vision-commentary on current status and future prospects. Eye (Lond). 2021 May 27. doi: 10.1038/s41433-021-01592-0. Epub ahead of print. PMID: 34045684.
Mactier H, Hamilton R, 2020: Prenatal opioid exposure - Increasing evidence of harm.
Summary:
Prenatal opioid exposure adversely impacts upon fetal growth and places the newborn at risk of neonatal opioid withdrawal. The severity and duration of opioid withdrawal cannot be predicted in the individual baby and may be contributed to by other drugs including benzodiazepines and alcohol as well as cigarette smoking. Mitigating factors include breastfeeding, rooming in and absence of maternal polypharmacy.
Less well recognised are a variety of other complications associated with prenatal opioid exposure including epigenetic changes, effects on neurophysiological function and structural alterations to the developing brain. The visual system is significantly affected, with changes to both clinical and electrophysiological function persisting at least to mid-childhood. Longer term neurodevelopmental and behavioural outcomes are confounded by multiple factors including poverty, parent-child interaction and small study numbers, but systematic reviews consistently demonstrate poorer outcomes for those children and young people prenatally exposed to opioids. Crucially, manifestation of neonatal withdrawal is not a prerequisite for important long term problems including behavioural, emotional or motor function disorder, sensory or speech disorder, strabismus and nystagmus.
A body of evidence supports an independent adverse effect of prenatal opioid exposure upon fetal brain development, mediated via a systemic neuro-inflammatory process. Children prenatally exposed to opioids should remain under appropriate follow up, at least until school entry, as difficulties may only become apparent in mid-childhood. Future studies of the management of opioid use disorder in pregnancy, including maintenance methadone, must include longer term outcomes for the baby.
Citation and Link:
Mactier H, Hamilton R. Prenatal opioid exposure – Increasing evidence of harm. Early Hum Dev. 2020 Nov;150:105188. doi: 10.1016/j.earlhumdev.2020.105188. Epub 2020 Sep 10. PMID: 32958331.
Monnelly VJ, Hamilton R, Chappell FM, Mactier H, Boardman JP, 2019. Childhood neurodevelopment after prescription of maintenance methadone for opioid dependency in pregnancy: a systematic review and meta-analysis.
Abstract:
Aim:
To systematically review and meta-analyse studies of neurodevelopmental outcome of children born to mothers prescribed methadone in pregnancy.
Method:
MEDLINE, Embase, and PsycINFO were searched for studies published from 1975 to 2017 reporting neurodevelopmental outcomes in children with prenatal methadone exposure.
Results:
Forty-one studies were identified (2283 participants). Eight studies were amenable to meta-analysis: at 2 years the Mental Development Index weighted mean difference of children with prenatal methadone exposure compared with unexposed infants was −4.3 (95% confidence interval [CI] −7.24 to −1.63), and the Psychomotor Development Index weighted mean difference was −5.42 (95% CI −10.55 to −0.28). Seven studies reported behavioural scores and six found scores to be lower among methadone-exposed children. Twelve studies reported visual outcomes: nystagmus and strabismus were common; five studies reported visual evoked potentials of which four described abnormalities. Factors that limited the quality of some studies, and introduced risk of bias, included absence of blinding, small sample size, high attrition, uncertainty about polydrug exposure, and lack of comparison group validity.
Interpretation:
Children born to mothers prescribed methadone in pregnancy are at risk of neurodevelopmental problems but risk of bias limits inference about harm. Research into management of opioid use disorder in pregnancy should include evaluation of childhood neurodevelopmental outcome.
What this paper adds:
- Children born to opioid-dependent mothers prescribed methadone are at risk of neurodevelopmental impairment.
- Exposed infants have lower Mental Development Index and Psychomotor Development Index scores than unexposed children.
- Atypical visual evoked potentials, strabismus, and nystagmus have increased prevalence.
- Estimates of impairment may be biased by intermediate to poor quality evidence.
Citation and Link:
Monnelly VJ, Hamilton R, Chappell FM, Mactier H, Boardman JP. Childhood neurodevelopment after prescription of maintenance methadone for opioid dependency in pregnancy: a systematic review and meta-analysis. Dev Med Child Neurol. 2019 Jul;61(7):750-760. doi: 10.1111/dmcn.14117. Epub 2018 Dec 3. PMID: 30511742; PMCID: PMC6617808.
McGlone L, Hamilton R, McCulloch DL, MacKinnon JR, Bradnam M, Mactier H, 2014: Visual outcome in infants born to drug-misusing mothers prescribed methadone in pregnancy.
Abstract:
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.
McGlone L, Hamilton R, McCulloch DL, MacKinnon JR, Bradnam M, Mactier H. Visual outcome in infants born to drug-misusing mothers prescribed methadone in pregnancy. Br J Ophthalmol. 2014 Feb;98(2):238-45. doi: 10.1136/bjophthalmol-2013-303967. Epub 2013 Nov 18. PMID: 24246372.
McGlone L, Hamilton R, McCulloch DL, Boulton R, Bradnam MS, Weaver LT, Mactier H, 2013: Neonatal visual evoked potentials in infants born to mothers prescribed methadone.
Abstract:
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.
Citation and Link:
McGlone L, Hamilton R, McCulloch DL, Boulton R, Bradnam MS, Weaver LT, Mactier H. Neonatal visual evoked potentials in infants born to mothers prescribed methadone. Pediatrics. 2013 Mar;131(3):e857-63. doi: 10.1542/peds.2012-2113. Epub 2013 Feb 18. PMID: 23420924.
Mactier H, McGlone L, Hamilton R, MacKinnon JR, 2012: Neonatal abstinence syndrome can be a problem.
Hamilton R, McGlone L, MacKinnon JR, Russell HC, Bradnam MS, Mactier H, 2010: Ophthalmic, clinical and visual electrophysiological findings in children born to mothers prescribed substitute methadone in pregnancy.
Abstract:
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.
Citation and Link:
Hamilton R, McGlone L, MacKinnon JR, Russell HC, Bradnam MS, Mactier H. Ophthalmic, clinical and visual electrophysiological findings in children born to mothers prescribed substitute methadone in pregnancy. Br J Ophthalmol. 2010 Jun;94(6):696-700. doi: 10.1136/bjo.2009.169284. Epub 2010 Apr 21. PMID: 20410537.
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