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A guideline is proposed that comprises the minimum items to be reported in research studies involving an eye tracker and human or non-human primate participant(s). This guideline was developed over a 3-year period using a consensus-based process via an open invitation to the international eye tracking community. This guideline will be reviewed at maximum intervals of 4 years., (© 2023. The Author(s).)

Purpose: This feasibility study investigated the practicability of collecting and analyzing tear proteins from preterm infants at risk of retinopathy of prematurity (ROP). We sought to identify any tear proteins which might be implicated in the pathophysiology of ROP as well as prognostic markers., Methods: Schirmer's test was used to obtain tear samples from premature babies, scheduled for ROP screening, after parental informed consent. Mass spectrometry was used for proteomic analysis., Results: Samples were collected from 12 infants, which were all adequate for protein analysis. Gestational age ranged from 25 + 6 to 31 + 1 weeks. Postnatal age at sampling ranged from 19 to 66 days. One infant developed self-limiting ROP. Seven hundred one proteins were identified; 261 proteins identified in the majority of tear samples, including several common tear proteins, were used for analyses. Increased risk of ROP as determined by the postnatal growth ROP (G-ROP) criteria was associated with an increase in lactate dehydrogenase B chain in tears. Older infants demonstrated increased concentration of immunoglobulin complexes within their tear samples and two sets of twins in the cohort showed exceptionally similar proteomes, supporting validity of the analysis., Conclusions: Tear sampling by Schirmer test strips and subsequent proteomic analysis by mass spectrometry in preterm infants is feasible. A larger study is required to investigate the potential use of tear proteomics in identification of ROP., Translational Relevance: Tear sampling and subsequent mass spectrometry in preterm infants is feasible. Investigation of the premature tear proteome may increase our understanding of retinal development and provide noninvasive biomarkers for identification of treatment-warranted ROP.

Purpose: To establish the extent of agreement for ISCEV standard reference pattern reversal VEPs (prVEPs) acquired at three European centres, to determine any effect of sex, and to establish reference intervals from birth to adolescence., Methods: PrVEPs were recorded from healthy reference infants and children, aged 2 weeks to 16 years, from three centres using closely matched but non-identical protocols. Amplitudes and peak times were modelled with orthogonal quadratic and sigmoidal curves, respectively, and two-sided limits, 2.5th and 97.5th centiles, estimated using nonlinear quantile Bayesian regression. Data were compared by centre and by sex using median quantile confidence intervals. The 'critical age', i.e. age at which P100 peak time ceased to shorten, was calculated., Results: Data from the three centres were adequately comparable. Sex differences were not clinically meaningful. The pooled data showed rapid drops in P100 peak time which stabilised by 27 and by 34 weeks for large and small check widths, respectively. Post-critical-age reference limits were 87-115 ms and 96-131 ms for large and small check widths, respectively. Amplitudes varied markedly and reference limits for all ages were 5-57 μV and 3.5-56 μV for large and small check widths, respectively., Conclusions: PrVEP reference data could be combined despite some methodology differences within the tolerances of the ISCEV VEP Standard, supporting the clinical benefit of ISCEV Standards. Comparison with historical data is hampered by lack of minimum reporting guidelines. The reference data presented here could be validated or transformed for use elsewhere., (© 2023. The Author(s).)

This document developed by the International Society for Clinical Electrophysiology of Vision (ISCEV) provides guidance for calibration and verification of stimulus and recording systems specific to clinical electrophysiology of vision. This guideline provides additional information for those using ISCEV Standards and Extended protocols and supersedes earlier Guidelines. The ISCEV guidelines for calibration and verification of stimuli and recording instruments (2023 update) were approved by the ISCEV Board of Directors 01, March 2023., (© 2023. The Author(s).)

Background/objectives: Remote assessment of children's visual acuity became necessary during the COVID-19 pandemic. This study aimed to assess the extent of agreement between hospital-based clinical testing and clinician-led home-based testing., Subjects/methods: 50 children aged 2-16 (median 8) years attending hospital eye services at two UK hospitals had routine hospital-based acuities compared with subsequent online, orthoptist-supervised home visual acuities. Agreement was assessed using intra-class correlation and Bland-Altman plots, as was test-retest (TRT) agreement of two, repeated home acuity tests., Results: Monocular acuities tested at hospital and at home were obtained from all 50 children; 33 also had binocular acuities in both settings and 35 had acuities retested immediately at home. Most children were tested at home using a computer or tablet; two were tested with a smartphone. No mean test differences were found for hospital vs home testing (-0.004 (95% CI -0.06-0.05) and -0.008 (95% CI -0.04-0.03) for binocular and monocular testing, respectively). Limits of agreement (LOAs) were ±0.32 and ±0.35 logMAR for binocular and monocular testing, respectively. LOAs for inter-ocular acuity differences (hospital vs home) were -0.15-0.25 logMAR. TRT monocular acuity agreement was excellent, with an LOA of ±0.14 logMAR., Conclusions: We found good (binocular) and excellent (monocular) agreement between hospital and home acuity testing. LOAs were in keeping with multiple changes between measures (test; setting; time; tester) and a cohort including patients as young as two years old. Even smartphone testing proved feasible. Inability of the supervising orthoptist to check test distance or device calibration/orientation was a limitation, likely contributing to the breadth of LOAs. Home vision testing is feasible and accurate, but its precision, acceptability, health economic impact and carbon impact require more attention., Competing Interests: The authors have no competing interests to declare., (Copyright: © 2023 The Author(s).)

Aim: The aim of this study was to examine executive function and emotional and behavioural difficulties of children aged between 8 and 10 years who had been prenatally exposed to methadone, compared to non-exposed peers., Methods: Prospective study: third follow-up of an original cohort of 153 children born to methadone-maintained opioid-dependent mothers 2008-2010: previous investigations were at 1-3 days and at 6-7 months of age. Carers completed the Strength and Difficulties Questionnaire (SDQ) and the Behaviour Rating Inventory of Executive Function, Second Edition (BRIEF®2). Results were compared between exposed and non-exposed groups., Results: Carers of 33 of 144 traceable children completed the measures. SDQ responses showed no group differences on subscales of emotional symptoms, conduct problems, or peer relationship problems. A marginally higher proportion of exposed children had a high or very high hyperactivity subscale score. Exposed children scored significantly higher on BRIEF®2 behavioural, emotional, and cognitive regulation indices, and on the global executive composite. After controlling for potentially confounding higher reported maternal tobacco use in the exposed group via regression modelling, the effect of methadone exposure reduced., Interpretation: This study supports evidence that methadone exposure in utero is associated with adverse neurodevelopmental outcomes in childhood. Challenges in studying this population include difficulties with long-term follow-up and controlling for potentially confounding factors. Further investigation of the safety of methadone and other opioids in pregnancy must include consideration of maternal tobacco use., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Spowart, Reilly, Mactier and Hamilton.)

The full-field electroretinogram (ERG) is a mass electrophysiological response to diffuse flashes of light and is used widely to assess generalized retinal function. This document, from the International Society for Clinical Electrophysiology of Vision (ISCEV), presents an updated and revised ISCEV Standard for clinical ERG testing. Minimum protocols for basic ERG stimuli, recording methods and reporting are specified, to promote consistency of methods for diagnosis, monitoring and inter-laboratory comparisons, while also responding to evolving clinical practices and technology. The main changes in this updated ISCEV Standard for clinical ERGs include specifying that ERGs may meet the Standard without mydriasis, providing stimuli adequately compensate for non-dilated pupils. There is more detail about analysis of dark-adapted oscillatory potentials (OPs) and the document format has been updated and supplementary content reduced. There is a more detailed review of the origins of the major ERG components. Several tests previously tabulated as additional ERG protocols are now cited as published ISCEV extended protocols. A non-standard abbreviated ERG protocol is described, for use when patient age, compliance or other circumstances preclude ISCEV Standard ERG testing., (© 2022. The Author(s).)

This case report describes a girl who presented antenatal arthrogryposis and postnatal hypotonia, generalized and respiratory weakness, joint deformities particularly affecting the lower limbs and poor swallow. By 5 months, cataracts, abnormal electroretinograms, visual evoked potentials (VEPs) and global developmental impairments were recognized. No causative variants were identified on targeted gene panels. After her unexpected death at 11 months, gene-agnostic trio whole exome sequencing revealed a likely pathogenic de novo BICD2 missense variant, NM_001003800.1, c.593T>C, p.(Leu198Pro), confirming the diagnosis of spinal muscular atrophy lower extremity predominant type 2 (SMA-LED2). We propose that cataract, abnormal electroretinograms and VEPs are novel features of SMA-LED2.

Introduction: Establishing robust reference intervals for clinical procedures has received much attention from international clinical laboratories, with approved guidelines. Physiological measurement laboratories have given this topic less attention; however, most of the principles are transferable., Methods: Herein, we summarise those principles and expand them to cover bilateral measurements and one-tailed reference intervals, which are common issues for those interpreting clinical visual electrophysiology tests such as electroretinograms (ERGs), visual evoked potentials (VEPs) and electrooculograms (EOGs)., Results: The gold standard process of establishing and defining reference intervals, which are adequately reliable, entails collecting data from a minimum of 120 suitable reference individuals for each partition (e.g. sex, age) and defining limits with nonparametric methods. Parametric techniques may be used under some conditions. A brief outline of methods for defining reference limits from patient data (indirect sampling) is given. Reference intervals established elsewhere, or with older protocols, can be transferred or verified with as few as 40 and 20 suitable reference individuals, respectively. Consideration is given to small numbers of reference subjects, interpretation of serial measurements using subject-based reference values, multidimensional reference regions and age-dependent reference values. Bilateral measurements, despite their correlation, can be used to improve reference intervals although additional care is required in computing the confidence in the reference interval or the reference interval itself when bilateral measurements are only available from some of subjects., Discussion: Good quality reference limits minimise false-positive and false-negative results, thereby maximising the clinical utility and patient benefit. Quality indicators include using appropriately sized reference datasets with appropriate numerical handling for reporting; using subject-based reference limits where appropriate; and limiting tests for each patient to only those which are clinically indicated, independent and highly discriminating., (© 2021. The Author(s).)

Clinical Relevance: Following the COVID-19 lockdown, uptake of slitlamp-enabled live teleophthalmology increased. Its use contributed to a reduction of referrals escalated to secondary care during-lockdown (avoided: 64% pre-lockdown vs 86% during-lockdown)., Background: Live teleophthalmology using video conferencing allows real-time, three-way consultation between secondary care, community providers and patients, improving interpretation of slit lamp findings and potentially reducing referrals to secondary care. NHS Forth Valley implemented live teleophthalmology in March 2019. In March 2020, the COVID-19 pandemic created urgency to deliver ophthalmic care while minimising the risk of contracting or spreading the disease. We aim to compare the uptake and two outcomes (number of avoided secondary care referrals; pattern of presenting conditions) of live teleophthalmology consultations in NHS Forth Valley before and during the COVID-19 national lockdown., Methods: An NHS secure video conferencing platform connected the video slit lamps of optometrists, or an iPad mounted on a slit lamp and viewing through the eyepieces, to a secondary care ophthalmologist via a virtual live clinic/waiting area. Data about avoiding a secondary care referral were extracted from a post-consultation ophthalmologist survey for 14 months of data. Pre- and during-lockdown intervals were before/after 23 March 2020, when routine eyecare appointments were suspended. Numbers of avoided referrals to secondary care and patterns of presenting conditions were compared for pre- and during-lockdown periods., Results: The COVID-19 pandemic markedly increased use of live teleophthalmology in NHS Forth Valley. Surveys were completed for 164 of 250 (66%) teleophthalmology consultations over the study period. Data from 154 surveys were analysed, 78 and 76 for the pre- and during-lockdown periods, respectively. Significantly more during-lockdown (86%) than pre-lockdown (64%; difference 21%, 95% CI 8-34%, p = 0.001) surveys indicated that referrals to secondary care were avoided., Conclusion: Survey data from ophthalmologists suggest significantly fewer escalations to secondary care due to teleophthalmology use.

The International Society for Clinical Electrophysiology of Vision (ISCEV) standard for visual evoked potentials (VEPs) describes a minimum procedure for clinical VEP testing and encourages more extensive testing. This ISCEV extended protocol is an extension to the VEP standard. It describes procedures for recording multiple VEPs to a range of sizes of pattern stimuli to establish the VEP spatial frequency limit (threshold) and for relating this limit to visual acuity.

Purpose: Visual evoked potentials (VEPs) can be used to measure visual resolution via a spatial frequency (SF) limit as an objective estimate of visual acuity. The aim of this systematic review is to collate descriptions of the VEP SF limit in humans, healthy and disordered, and to assess how accurately and precisely VEP SF limits reflect visual acuity., Methods: The protocol methodology followed the PRISMA statement. Multiple databases were searched using "VEP" and "acuity" and associated terms, plus hand search: titles, abstracts or full text were reviewed for eligibility. Data extracted included VEP SF limits, stimulus protocols, VEP recording and analysis techniques and correspondence with behavioural acuity for normally sighted healthy adults, typically developing infants and children, healthy adults with artificially degraded vision and patients with ophthalmic or neurological conditions., Results: A total of 155 studies are included. Commonly used stimulus, recording and analysis techniques are summarised. Average healthy adult VEP SF limits vary from 15 to 40 cpd, depend on stimulus, recording and analysis techniques and are often, but not always, poorer than behavioural acuity measured either psychophysically with an identical stimulus or with a clinical acuity test. The difference between VEP SF limit and behavioural acuity is variable and strongly dependent on the VEP stimulus and choice of acuity test. VEP SF limits mature rapidly, from 1.5 to 9 cpd by the end of the first month of life to 12-20 cpd by 8-12 months, with slower improvement to 20-40 cpd by 3-5 years. VEP SF limits are much better than behavioural thresholds in the youngest, typically developing infants. This difference lessens with age and reaches equivalence between 1 and 2 years; from around 3-5 years, behavioural acuity is better than the VEP SF limit, as for adults. Healthy, artificially blurred adults had slightly better behavioural acuity than VEP SF limits across a wide range of acuities, while adults with heterogeneous ophthalmic or neurological pathologies causing reduced acuity showed a much wider and less consistent relationship. For refractive error, ocular media opacity or pathology primarily affecting the retina, VEP SF limits and behavioural acuity had a fairly consistent relationship across a wide range of acuity. This relationship was much less consistent or close for primarily macular, optic nerve or neurological conditions such as amblyopia. VEP SF limits were almost always normal in patients with non-organic visual acuity loss., Conclusions: The VEP SF limit has great utility as an objective acuity estimator, especially in pre-verbal children or patients of any age with motor or learning impairments which prevent reliable measurement of behavioural acuity. Its diagnostic power depends heavily on adequate, age-stratified, reference data, age-stratified empirical calibration with behavioural acuity, and interpretation in the light of other electrophysiological and clinical findings. Future developments could encompass faster, more objective and robust techniques such as real-time, adaptive control., Registration: International prospective register of systematic reviews PROSPERO ( https://www.crd.york.ac.uk/PROSPERO/ ), registration number CRD42018085666.

Purpose: Acuity tests for infants and young children use preferential looking methods that require a perceptual match of brightness and color between grey background and target spatial average. As a first step in exploring this matching, this article measures photometric and colorimetric matches in these acuity tests., Methods: The luminance, uniformity, contrast, and color spectra of Teller Acuity Cards, Keeler Acuity Cards for Infants, and Lea Paddles under ambient, warm, and cold lighting, and of grey-emulating patterns on four digital displays, were measured. Five normal adults' acuities were tested at 10 m observationally., Results: Luminance and spectral mismatches between target and background were found for the printed tests (Weber contrasts of 0.3% [Teller Acuity Cards], -1.7% [Keeler Acuity Cards for Infants], and -26% [Lea Paddles]). Lighting condition had little effect on contrast, and all printed tests and digital displays met established adult test luminance and uniformity standards. Digital display grey backgrounds had very similar luminance and color whether generated by a checkerboard, vertical grating, or horizontal grating. Improbably good psychophysical acuities (better than -0.300 logMAR: (logarithm of the minimum angle of resolution)) were recorded from adults using the printed tests at 10 m, but not using the digital test Peekaboo Vision., Conclusions: Perceptible contrast between target and background could lead to an incorrectly measured, excessively good acuity. It is not clear whether the luminance and spectral contrasts described here have clinically meaningful consequences for the target patient group, but they may be avoidable using digital tests., Translational Relevance: Current clinical infant acuity tests present photometric mismatches that may return inaccurate testing results., Competing Interests: Disclosure: G. Vivas-Mateos, None; I.A.T. Livingstone, None; R. Hamilton, None; A. Cheema, None; M.E. Giardini, None, (Copyright 2020 The Authors.)

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., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

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., (© 2018 The Authors. Developmental Medicine & Child Neurology published by John Wiley & Sons Ltd on behalf of Mac Keith Press.)

The International Society for Clinical Electrophysiology of Vision (ISCEV) standard for full-field electroretinography (ERG) describes a minimum protocol for clinical testing but encourages additional ERG testing when appropriate. This ISCEV extended protocol describes methods to record and evaluate a light-adapted (LA) ERG stimulus-response series with increasing flash strengths. The LA ERG stimulus-response series (also referred to as the luminance-response or intensity-response series in the published literature) can characterise generalised cone system function more comprehensively than the ISCEV standard LA ERGs alone. The amplitude of LA ERG a-waves, arising from cones and cone off-bipolar cells, typically shows a saturating function. The LA ERG b-wave amplitudes, which arise primarily from activity of retinal bipolar cells, show an amplitude peak followed by a nonzero plateau (the "photopic hill" phenomenon). This ISCEV extended protocol specifies a stimulus-response series suitable to evaluate generalised dysfunction affecting the LA retina, to aid in distinguishing between the on- and off-responses of the cone system and to monitor ERG changes in these characteristics. The LA ERG stimulus-response series for a- and b-waves is recorded to a sequence of nine flash stimuli ranging from 0.03 to 300 cd s m -2 , superimposed on a standard background of 30 cd m -2 . A shorter protocol is also presented to measure the mid-range of the function (the "photopic hill") using 5 flash stimuli.

Barley is naturally an inbreeding hermaphrodite plant so that each generation resembles its parental generation. New variation can be introduced by crossing parents that complement each other for desirable or target characteristics but requires human intervention to ensure that all the resulting seeds are hybrids of the two parents. That means that plants selected to be female parents have to be emasculated and are then fertilized with pollen from plants selected to be male parents. Here we describe how to emasculate and pollinate barley plants with a method that can be used either in the glasshouse or in the field.

The International Society for Clinical Electrophysiology of Vision (ISCEV) standard for full-field electroretinography (ERG) describes a minimum procedure, but encourages more extensive testing. This ISCEV extended protocol describes an extension to the ERG standard, namely the dark-adapted (DA) red flash ERG. The DA red flash ERG can be incorporated conveniently within the ISCEV standard ERG protocol after a minimum of 20-min DA and recorded after the DA 0.01 ERG to a flash strength of 0.3 phot cd s m -2 , eliciting a waveform with two positive peaks in healthy individuals. The first positive component is the cone-mediated x-wave with a peak at 30-50 ms; the second is a rod-mediated b-wave with a peak time of approximately 100 ms. Shorter DA times may be desirable to shorten the recording time or to alter the prominence of the early cone-mediated x-wave relative to the rod-mediated b-wave. The DA red flash ERG is used to aid the diagnosis of achromatopsia (rod monochromacy), cone dystrophy and other forms of cone system dysfunction, including "Bradyopsia" (RGS9/R9AP-retinopathy), when the DA red flash ERG x-wave is preserved in the absence of ISCEV standard LA ERGs. The DA red flash ERG can also help determine the origin of residual DA ERGs in cases of severe rod dysfunction, for example in disorders such as vitamin A deficiency, fundus albipunctatus (RDH5-retinopathy), Oguchi disease (SAG- or GRK1-retinopathy) and some rod-cone dystrophies. To shorter DA periods, the x-wave may be elicited without the following rod b-wave, shown to be helpful in abbreviated protocols for children.

Purpose: To evaluate two builds of the digital grating acuity test, "Peekaboo Vision" (PV), in young (6-60 months) populations in two hospital settings (Malawi and United Kingdom)., Methods: Study 1 evaluated PV in Blantyre, Malawi ( N = 58, mean age 33 months); study 2 evaluated an updated build in Glasgow, United Kingdom ( N = 60, mean age 44 months). Acuities were tested-retested with PV and Keeler Acuity Cards for Infants (KACI). Bland-Altman techniques were used to compare results and repeatability. Child engagement was compared between groups. Study 2 included test-time comparison., Results: Study 1 (Malawi): The mean difference between PV and KACI was 0.02 logMAR with 95% limits of agreement (LoA) of 0.33 to 0.37 LogMAR. On test-retest, PV demonstrated 95% LoA of -0.283 to 0.198 logMAR with coefficient of repeatability (CR) 0.27. KACI demonstrated 95% LoA of -0.427 to 0.323 logMAR, and larger CR was 0.37. PV evidenced higher engagement scores than KACI ( P = 0.0005). Study 2 (UK): The mean difference between PV and KACI was 0.01 logMAR; 95% LoA was -0.413 to 0.437 logMAR. Again, on test-retest, PV had narrower LoA (-0.344 to 0.320 logMAR) and lower CR (0.32) versus KACI, with LoA -0.432 to 0.407 logMAR, CR 0.42. The two tests did not differ in engagement score ( P = 0.5). Test time was ∼1 minute shorter for PV (185 vs. 251 s, P = 0.0021)., Conclusions: PV gives comparable results to KACI in two pediatric populations in two settings, with benefits in repeatability indices and test duration., Translational Relevance: Leveraging tablet technology extends reliable infant acuity testing to bedside, home, and rural settings, including areas where traditional equipment cannot be financed.

This document, from the International Society for Clinical Electrophysiology of Vision (ISCEV), presents an updated and revised ISCEV Standard for full-field clinical electroretinography (ffERG or simply ERG). The parameters for Standard flash stimuli have been revised to accommodate a variety of light sources including gas discharge lamps and light emitting diodes. This ISCEV Standard for clinical ERGs specifies six responses based on the adaptation state of the eye and the flash strength: (1) Dark-adapted 0.01 ERG (rod ERG); (2) Dark-adapted 3 ERG (combined rod-cone standard flash ERG); (3) Dark-adapted 3 oscillatory potentials; (4) Dark-adapted 10 ERG (strong flash ERG); (5) Light-adapted 3 ERG (standard flash "cone" ERG); and (6) Light-adapted 30 Hz flicker ERG. ISCEV encourages the use of additional ERG protocols for testing beyond this minimum standard for clinical ERGs.

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.

Purpose: Although premature birth is recognised as a cause of cerebral visual impairment (CVI), which can include cerebral visual dysfunction (CVD), the incidence and nature of CVD in prematurely born children is not known., Methods: A prospective, controlled investigation was undertaken of forty-six, mainstream primary school children, prematurely born with gestations of 24.0-34.6 weeks, and of 130 control (term-born) children. Assessments were made of IQ, ophthalmic functions, visual perception and visual attention. Structured history-taking seeking evidence of behavioural features of CVI used a question inventory. Obstetric, neonatal and paediatric medical histories were documented from case records., Results: Fifteen out of forty-six (33 %) of the prematurely born children-"cluster A"-revealed behaviours corresponding with CVD on cluster analysis of the CVI inventory. The whole prematurely born group performed worse than controls on all visual perception tests and all four visual attention tests. Children in cluster A were responsible for this effect, performing worse than controls on all visual perception and visual attention tests except visual closure, while cluster B prematurely born children performed no differently to controls., Conclusions: The prevalence of CVD in these prematurely born children is between 21-47 % (95 % CI), with a pattern similar to "dorsal stream dysfunction". Currently available perceptual tests appear to be unable to identify the specific pattern of problems noted in this group. Many studies have provided evidence of cognitive and intellectual dysfunction in prematurely born children, and it is possible that CVD is a contributor. The CVI inventory is a potential means of identifying and characterising the condition, which can be ameliorated with simple strategies.

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.

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.

Steady-state VEPs to full-field flicker (FFF) using sinusoidally modulated light were compared with those elicited by square-wave modulated light across a wide range of stimulus frequencies with monocular and binocular FFF stimulation. Binocular and monocular VEPs were elicited in 12 adult volunteers to FFF with two modes of temporal modulation: sinusoidal or square-wave (abrupt onset and offset, 50% duty cycle) at ten temporal frequencies ranging from 2.83 to 58.8 Hz. All stimuli had a mean luminance of 100 cd/m(2) with an 80% modulation depth (20-180 cd/m(2)). Response magnitudes at the stimulus frequency (F1) and at the double and triple harmonics (F2 and F3) were compared. For both sinusoidal and square-wave flicker, the FFF-VEP magnitudes at F1 were maximal for 7.52 Hz flicker. F2 was maximal for 5.29 Hz flicker, and F3 magnitudes are largest for flicker stimulation from 3.75 to 7.52 Hz. Square-wave flicker produced significantly larger F1 and F2 magnitudes for slow flicker rates (up to 5.29 Hz for F1; at 2.83 and 3.75 Hz for F2). The F3 magnitudes were larger overall for square-wave flicker. Binocular FFF-VEP magnitudes are larger than those of monocular FFF-VEPs, and the amount of this binocular enhancement is not dependant on the mode of flicker stimulation (mean binocular: monocular ratio 1.41, 95% CI: 1.2-1.6). Binocular enhancement of F1 for 21.3 Hz flicker was increased to a factor of 2.5 (95% CI: 1.8-3.5). In the healthy adult visual system, FFF-VEP magnitudes can be characterized by the frequency-response functions of F1, F2 and F3. Low-frequency roll-off in the FFF-VEP magnitudes is greater for sinusoidal flicker than for square-wave flicker for rates ≤ 5.29 Hz; magnitudes for higher-frequency flicker are similar for the two types of flicker. Binocular FFF-VEPs are larger overall than those recorded monocularly, and this binocular summation is enhanced at 21.3 Hz in the mid-frequency range.

In response to progressively stronger flashes delivered against a rod saturating background light, the amplitude of the photopic ERG b-wave first increases, reaches a maximal value (V (max)) and then decreases gradually to a plateau where the amplitude of the b-wave equals that of the a-wave, a phenomenon known as the photopic hill (PH). The purpose of this study was to investigate how the PH grew during the course of the light adaptation (LA) process that follows a period of dark adaptation (DA): the so-called light adaptation effect (LAE). Photopic ERG (time-integrated) luminance-response (LR) functions were obtained prior to (control-fully light adapted) and at 0, 5 and 10 min of LA following a 30-min period of DA. A mathematical model combining a Gaussian and a logistic growth function, suggested to reflect the OFF and ON retinal contribution to the PH respectively, was fitted to the LR functions thus obtained. Our results indicate that the magnitude of the cone ERG LAE is modulated by the stimulus luminance, with b-wave enhancements being maximal for luminance levels that result in the descent of the PH. The Gaussian function grew significantly with LA while the logistic growth function remained basically unchanged. Our findings would therefore suggest that the LAE reflects primarily an increase in the retinal OFF response during LA.

This study characterizes differences in human ERGs based on ocular pigmentation. Light- and dark-adapted luminance-response (LR) series for a-, b- and i-waves and light-adapted oscillatory potentials (OPs) were recorded in 14 healthy volunteers (7 blue-eyed Caucasians; 7 brown-eyed Asians, aged 20-22 years). Amplitude interpolations were by logistic growth (Naka-Rushton), Gaussian or the combined 'photopic hill' functions. Implicit times (IT) for dark-adapted a- and b-waves, and for light-adapted a-, b- and i-waves were earlier in the blue-eyed group than in the brown-eyed group across all flash strengths (P < 0.05). For dark-adapted ERGs, saturated a-wave amplitude was larger for blue eyes (397 vs. 318 μV, P < 0.05) as was the a-wave to strong flash (10 cd·s/m(2); 357 vs. 293 μV, P < 0.05) and the b-wave to ISCEV standard 0.01 (354 vs. 238 μV, P < 0.05). Light-adapted b-waves for midrange flash stimuli were much larger for the blue-eyed group (photopic hill, Gaussian peak: 155 vs. 82 μV, P < 0.001) with no difference in saturated amplitudes. Similarly, interpolated i-wave amplitudes were larger (48 vs. 18 μV, P < 0.01). For a light-adapted 2.6 stimulus, a- and b-waves were larger for the blue-eyed group (52 vs. 39 μV; 209 vs. 133 μV, P < 0.01) as were OP4 and OP5 (37.2 vs. 15.6 μV; 47.5 vs. 22.2 μV, P < 0.01), but OP1-OP3 did not differ. ERGs have shorter ITs in people with blue irides than in those with dark pigmentation. Amplitude differences are highly non-linear and substantially larger from eyes with light pigmentation for components thought to be associated with the OFF retinal pathways.

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.

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.

Parasites represent a major threat to all organisms which has led to the evolution of an array of complex and effective defence mechanisms. Common to both vertebrates and invertebrates are innate immune mechanisms that can be either constitutively expressed or induced on exposure to infection. In nature, we find that a combination of both induced and constitutive responses are employed by vertebrates, invertebrates and, to an extent, plants when they are exposed to a parasite. Here we use a simple within-host model motivated by the insect immune system, consisting of both constitutive and induced responses, to address the question of why both types of response are maintained so ubiquitously. Generally, induced responses are thought to be advantageous because they are only used when required but are too costly to maintain constantly, while constitutive responses are advantageous because they are always ready to act. However, using a simple cost function but with no a priori assumptions about relative costs, we show that variability in parasite growth rates selects for a strategy that combines both constitutive and induced defences. Differential costs are therefore not necessary to explain the adoption of both forms of defence. Clearly, hosts are likely to be challenged by variable parasites in nature and this is sufficient to explain why it is optimal to deploy both arms of the innate immune system.

Understanding the processes that shape the genetic structure of parasite populations and the functional consequences of different parasite genotypes is critical for our ability to predict how an infection can spread through a host population and for the design of effective vaccines to combat infection and disease. Here, we examine how the genetic structure of parasite populations responds to host genetic heterogeneity. We consider the well-characterized molecular specificity of major histocompatibility complex binding of antigenic peptides to derive deterministic and stochastic models. We use these models to ask, firstly, what conditions favour the evolution of generalist parasite genotypes versus specialist parasite genotypes? Secondly, can parasite genotypes coexist in a population? We find that intragenomic interactions between parasite loci encoding antigenic peptides are pivotal in determining the outcome of evolution. Where parasite loci interact synergistically (i.e. the recognition of additional antigenic peptides has a disproportionately large effect on parasite fitness), generalist parasite genotypes are favoured. Where parasite loci act multiplicatively (have independent effects on fitness) or antagonistically (have diminishing effects on parasite fitness), specialist parasite genotypes are favoured. A key finding is that polymorphism is not stable and that, with respect to functionally important antigenic peptides, parasite populations are dominated by a single genotype.

Background: Heart rate variability (HRV) recorded over 5 min or 24 h is used increasingly to measure autonomic function and as a prognostic indicator in cardiology. Measuring HRV during a standard 10-s ECG would save time and cut costs. The aim of this study, therefore, was to discover whether indices of HRV calculated over 10 s could predict cardiac vagal tone (CVT) recorded over a 5-min period by the NeuroScope, a new instrument that selectively measures vagal tone., Methods: A total of 50 subjects had ECGs taken at the beginning, middle and end of a 5-min measurement of CVT. Standard deviation of normal-to-normal RR interval (SDNN), root mean square of successive differences in RR intervals (rMSSD), and the average absolute difference (AAD) in RR intervals were calculated from RR intervals derived from the ECGs. Subjects were divided into a training set (n=40) and a test set (n=10)., Results: Regression equations derived from the training set predicted 5-min mean CVT in the test set with r(2) of 95.8%, 92.9% and 87.9% for AAD, rMSSD and SDNN, respectively. Indices obtained from the third ECG in each set tended to give a closer relationship with CVT than those derived from the first and second ECGs: this could be because of the greater spread of the independent variables in the third set. An underlying linear physiological phenomenon could not be excluded, however, without continuing the measurements over a longer time., Conclusions: These results demonstrate that AAD and rMSSD calculated from a 10-s ECG can accurately predict 5-min mean CVT as measured by the NeuroScope.

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.