ObjectiveWe present the protocol of a prospective scoping review which aims to understand how multi-channel visual evoked potentials (mcVEPs) are used to investigate congenital chiasmal misrouting and what outcomes are measured, interpreted and reported.IntroductionmcVEPs are used for the objective evaluation of chiasmal misrouting, which is characterized by a crossed asymmetry in the distribution of cortical responses over each hemisphere during monocular stimulation, and is often observed in patients with albinism. The application and analysis of mcVEPs varies across centers, creating a need to explore the range of practice regarding their conduct and reporting and to identify potential areas for adaptation or optimization or guidelines for specific populations.Inclusion criteriaPeer reviewed and grey literature on the use of mcVEP to detect chiasmal misrouting in humans with non-acquired pathologies will be considered. All literature providing details of mcVEP methodology for replication and specification of chiasmal misrouting will be included for review.MethodsSearches will be conducted using MEDLINE, Embase, Cochrane and Web of Science with the expertise of a librarian. The search will be conducted with no limitation on time period, but will be restricted to the Latin alphabet. Titles and abstracts will be screened by two investigators with conflicts resolved by a third investigator. Included articles will proceed with data extraction on study details including methodology, design, and outcomes. The results will be synthesized and mapped for logical understanding.

Incomplete congenital stationary night blindness (icCSNB) is a subtype of inherited, non-progressive retinal diseases. Most cases of icCSNB result from mutations in the X-linked gene CACNA1F. We describe the clinical findings of two male siblings diagnosed with icCSNB, both carrying a novel variant c.4008 + 5G > T in CACNA1F inherited from their mother. We carried out a comprehensive ophthalmic assessment, including fundus imaging, optical coherence tomography (OCT) scanning and electroretinography. We performed genetic testing with next generation sequencing, in-silico and functional analyses to further characterise the novel variant. Two male siblings presented with high myopia and reduced visual acuities at age three. Examination and OCT demonstrated no significant abnormalities in both siblings. Full-field electroretinogram (ffERG) testing demonstrated markedly reduced amplitude to weak flashes and an electronegative waveform to strong flashes in dark-adapted ERGs, resembling that of icCSNB, leading to its diagnosis in both children. Next generation sequencing in the older sibling identified a novel hemizygous c.4008 + 5G > T variant in CACNA1F. In-silico analysis of this variant predicted that it would disrupt normal splicing of CACNA1F, though it was not possible to confirm this by RNA sequencing. This same variant was found in the younger sibling, as well as in their mother who had normal examination and ffERG findings. We report a novel CACNA1F variant not previously identified in the literature in three patients. Although functional analyses were unable to confirm pathogenicity of this variant, in-silico tools predicted that its effect is consistent with the pathogenesis of icCSNB. Reporting of this family further widens the genotypic spectrum of icCSNB.

BACKGROUND/OBJECTIVES:The Honey Rose trial increased referrals for suspected papilloedema. We audited such referrals from community optometrists and used long-term patient outcomes to investigate the diagnostic accuracy of OCT retinal nerve fibre layer (RNFL) thickness and B scan ultrasound optic nerve sheath diameter (ONSD) for raised intracranial pressure (rICP). SUBJECTS/METHODS:Audit of 337 children seen in a 'blurry disc' clinic. Long-term outcomes (6-42 months) were used to classify children as with or without raised ICP. Receiver operating curves investigated diagnostic accuracy of RNFL and ONSD cut-off values. Regression modelling investigated potential predictive variables for rICP. RESULTS:310/337 children (92%) were discharged, 75 of whom were reviewed due to some clinical suspicion. 27/337 children (8%) were referred to other specialists, of whom 18 had rICP (16 IIH, one intra-cranial tumour, one arachnoid cyst). RNFL thickness cut-off >144 µm at 95% specificity had 83% sensitivity (95% CI 61-100%) and ONSD cut-off >4.99 mm at 90% specificity had 82% sensitivity (95% CI 50-100%) for rICP. Increased RNFL thickness, increased ONSD and presence of symptoms all contributed to prediction of rICP: acuity, age, sex and all other OCT parameters did not. CONCLUSIONS:95% (319/337) of children referred with suspected papilloedema did not have raised ICP. Almost three-quarters of children referred (253/337, 70%) would have been more appropriately managed in community optometry. OCT RNFL and ONSD cut-offs show promising diagnostic accuracy for rICP in this study. There is a clear need to support community optometry to resume management of most children with suspected papilloedema.

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.

Background Very premature infants screened for retinopathy of prematurity (ROP) that do not develop ROP still experience serious visual developmental challenges, and while it is recommended that all children in the UK are offered preschool visual screening, we aimed to explore whether this vulnerable group requires dedicated follow-up.Methods We performed a real-world retrospective observational cohort study of children previously screened for ROP in NHS Greater Glasgow and Clyde (Scotland) between 2013 and 2015. We excluded those with any severity of ROP identified during screening. Electronic patient records were searched for preschool orthoptic visual screening (See4School) results and results of referral to the hospital eye service (HES).Results 222 children met the inclusion criteria. Their median birth weight was 1200 g and median gestational age was 31 weeks. A total of 111 (50%) of these children had been referred to HES nationally. 103 were referred within the health board where ROP screening took place; of these, 47% (48/103) were referred from the See4School programme, 31% (31/103) from paediatric clinics, 13% (13/103) from primary care and 11% (11/103) from community optometrists. 42 of these 103 referrals (41%) to HES had occurred before the age (3½ years) when children became eligible for See4School screening. At hospital review, 55% (55/99) patients had a glasses prescription issued for refractive error, 22% were estimated to have amblyopia and 30% had a diagnosis of strabismus.Conclusion In this non-controlled study we found premature infants that do not develop ROP still face considerable visual morbidity and dedicated follow-up may be warranted.

Background/objectives To examine prevalence of failed visual assessment at 8–10 years in children born to methadone-maintained opioid dependent (MMOD) mothers and relate this to known in utero substance exposure. Subjects/methods Follow up of observational cohort study of methadone-exposed and comparison children matched for birthweight, gestation and postcode of residence at birth. Participants were 144 children (98 exposed, 46 comparison). Prenatal drug exposure was previously established via comprehensive maternal and neonatal toxicology. Children were invited to attend for visual assessment and casenotes were reviewed. Presence of acuity poorer than 0.2 logMAR, strabismus, nystagmus and/or impaired stereovision constituted a ‘fail’. Fail rates were compared between methadone-exposed and comparison children after adjusting for known confounding variables. Results 33 children attended in person: data were also derived from casenote review for all children. After controlling for maternal reported tobacco use, methadone-exposed children were more likely to have a visual ‘fail’ outcome, adjusted odds ratio 2.6, 95% CI 1.1–6.2; adjusted relative risk 1.8 (95% CI 1.1–3.4). Visual ‘fail’ outcome rates did not differ between methadone-exposed children who had ( n = 47) or had not ( n = 51) received pharmacological treatment for neonatal abstinence/opioid withdrawal syndrome (NAS/NOWS); fail rate 62% vs 53% (95% CI of difference—11–27%). Conclusions Children born to MMOD mothers are almost twice as likely as unexposed peers to have significant visual abnormalities at primary school age. Prenatal methadone exposure should be considered in the differential diagnosis of nystagmus. Findings support visual assessment prior to school entry for children with any history of prenatal opioid exposure. Trial registration The study was prospectively registered on ClinicalTrials.gov (NCT03603301), https://clinicaltrials.gov/ct2/show/NCT03603301 .

The full-field stimulus test (FST) is a psychophysical technique designed for the measurement of visual function in low vision. The method involves the use of a ganzfeld stimulator, as used in routine full-field electroretinography, to deliver full-field flashes of light. This guideline was developed jointly by the International Society for Clinical Electrophysiology of Vision (ISCEV) and Imaging and Perimetry Society (IPS) in order to provide technical information, promote consistency of testing and reporting, and encourage convergence of methods for FST. It is intended to aid practitioners and guide the formulation of FST protocols, with a view to future standardisation.

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.

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.

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.

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.

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.

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.

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.

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.