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Introduction Visual electrophysiology tests require the use of precise and calibrated visual display units (VDUs). Existing VDUs for presenting structured stimuli are now mostly obsolete, with modern solutions limited or unsuitable for clinical testing. Digital light processing (DLP) laser projectors have recently become commercially available and this study aimed to assess their suitability as VDUs for visual electrophysiology testing. Methods This study consisted of two sections. The first was a photometric study of two DLP laser projectors (Viewsonic LS831WU and HiSense 100L5FTUK) to assess luminance, contrast, spectral and temporal characteristics of the stimulus. The second was a physiological study comparing pattern electroretinograms (PERG) and visual evoked potentials (PVEPs) amplitudes and peak-times recorded using a DLP laser projector, photometrically and spatially matched to existing plasma VDUs at our institution (Pioneer Electronics Corporation, PDP422MXE). Results The Viewsonic DLP laser projector was capable of high luminance levels (0–587.5 cd/m2) whilst maintaining contrast above 93%. The temporal properties showed fast rise and fall times of 0.5–1 ms and 0.5–1 ms, respectively, without any transient luminance change with reversals. The device required a warm-up time of at least 2 min until reaching near maximal luminance. The second (Hisense) device was observed to have a detrimental input lag jitter so was not used for any further analysis. PERGs and PVEPs showed high agreement and correlation (r = 0.766–0.905) between the Viewsonic DLP device and existing plasma VDUs. No significant differences were observed for P50 and P100 peak-time (p = > 0.05), however P50, N95 and P100 amplitudes were all significantly larger for the DLP device (p = Discussion The DLP laser projector tested in this study is a viable and practical replacement VDU for clinical electrophysiology tests of vision. The device is easily capable of meeting ISCEV standards, and showed PERG and PVEP amplitudes larger than existing systems despite photometric and spatial matching. The DLP laser projectors are capable of very large field sizes so are beneficial for paediatric testing or those wishing to examine large field responses. Importantly, it was observed that some devices may suffer input lag jitter, therefore, individual calibration and assessment of DLP projection systems is an important consideration before clinical implementation.

Aims To assess the diagnostic accuracy of fundoscopy and visual evoked potentials (VEPs) in detecting intracranial hypertension (IH) in patients with craniosynostosis undergoing spring-assisted posterior vault expansion (sPVE). Methods Children with craniosynostosis undergoing sPVE and 48-hour intracranial pressure (ICP) monitoring were included in this single-centre, retrospective, diagnostic accuracy study. Data for ICP, fundoscopy and VEPs were analysed. Primary outcome measures were papilloedema on fundoscopy, VEP assessments and IH, defined as mean ICP > 20 mmHg. Diagnostic indices were calculated for fundoscopy and VEPs against IH. Secondary outcome measures included final visual outcomes. Results Fundoscopic examinations were available for 35 children and isolated VEPs for 30 children, 22 of whom had at least three serial VEPs. Sensitivity was 32.1% for fundoscopy (95% confidence intervals [CI]: 15.9–52.4) and 58.3% for isolated VEPs (95% CI 36.6–77.9). Specificity for IH was 100% for fundoscopy (95% CI: 59.0–100) and 83.3% for isolated VEPs (95% CI: 35.9–99.6). Where longitudinal deterioration was suspected from some prVEPs but not corroborated by all, sensitivity increased to 70.6% (95% CI: 44.0–89.7), while specificity decreased to 60% (95% CI: 14.7–94.7). Where longitudinal deterioration was clinically significant, sensitivity decreased to 47.1% (23.0–72.2) and specificity increased to 100% (47.8–100). Median final BCVA was 0.24 logMAR (n = 36). UK driving standard BCVA was achieved by 26 patients (72.2%), defined as ≥0.30 logMAR in the better eye. Conclusion Papilloedema present on fundoscopy reliably indicated IH, but its absence did not exclude IH. VEP testing boosted sensitivity at the expense of specificity, depending on method of analysis.

Background Late infantile neuronal ceroid lipofuscinosis (CLN2 Batten disease) is a rare, progressive neurodegenerative disease of childhood. The natural history of motor and language regression is used to monitor the efficacy of CNS treatments. Less is known about CLN2 retinopathy. Our aim is to elaborate the nature, age of onset, and symmetry of CLN2 retinopathy using visual electrophysiology and ophthalmic imaging. Subjects and methods We reviewed 22 patients with genetically confirmed CLN2 disease; seventeen showing classical and five atypical disease. Flash electroretinograms (ERGs), flash and pattern reversal visual evoked potentials (VEPs), recorded from awake children were collated. Available fundus images were graded, optical coherence tomography (OCT) central subfoveal thickness (CST) measured, and genotype, age, clinical vision assessment and motor language grades assembled. Results ERGs show cone/rod system dysfunction preceded by localised macular ellipsoid zone disruption on OCT from 4.8 years. Electroencephalogram (EEG) time-locked spikes confounded both pattern 6/17 (35%) and flash VEPs 12/16 (75%). Paired right eye (RE) and left eye (LE) ERG amplitudes did not differ significantly for each flash stimulus at the p 0.001 level, Wilcoxon ranked signed test. Cone ERGs show a functional deficit before CST thinning in classical disease. Optomap hyper fundus autofluorescence (FAF) at the fovea was noted in three patients with normal ERGs. The oldest patient showed an ovoid aggregate above the external limiting membrane at the fovea, which did not affect the PERG. Conclusion ERG findings in CLN2 retinopathy show symmetrical cone-rod dysfunction, from 4y10m in this series, but a broad range of ages when ERG function is preserved.

Clinical electrophysiological assessment of optic nerve and retinal ganglion cell function can be performed using the Pattern Electroretinogram (PERG), Visual Evoked Potential (VEP) and the Photopic Negative Response (PhNR) amongst other more specialised techniques. In this review, we describe these electrophysiological techniques and their application in diseases affecting the optic nerve and retinal ganglion cells with the exception of glaucoma. The disease groups discussed include hereditary, compressive, toxic/nutritional, traumatic, vascular, inflammatory and intracranial causes for optic nerve or retinal ganglion cell dysfunction. The benefits of objective, electrophysiological measurement of the retinal ganglion cells and optic nerve are discussed, as are their applications in clinical diagnosis of disease, determining prognosis, monitoring progression and response to novel therapies.摘要: 使用图形视网膜电流图 (Pattern Electroretinogram, PERG)、视觉诱发电位 (Visual Evoked Potential, VEP) 和感光阴性反应 (Photopic Negative Response, PhNR) 以及其他更专业的技术可以进行视神经和视网膜神经节细胞功能的临床电生理评估。本文中, 我们描述了这些电生理技术及其在除青光眼以外的影响视神经和视网膜神经节细胞疾病中的应用。讨论的疾病组包括遗传性、应力性、毒性/营养性、外伤性、血管性、炎性和颅内原因导致的视神经或视网膜神经节细胞功能障碍。本文讨论了客观的、电生理测量视网膜神经节细胞和视神经的优势, 以及它们在疾病的临床诊断、评估预后、监测进展和对新疗法的反应等方面的应用。.

Visual electrophysiology tests require the use of precise and calibrated visual display units (VDUs). Existing VDUs for presenting structured stimuli are now mostly obsolete, with modern solutions limited or unsuitable for clinical testing. Digital light processing (DLP) laser projectors have recently become commercially available and this study aimed to assess their suitability as VDUs for visual electrophysiology testing.This study consisted of two sections. The first was a photometric study of two DLP laser projectors (Viewsonic LS831WU and HiSense 100L5FTUK) to assess luminance, contrast, spectral and temporal characteristics of the stimulus. The second was a physiological study comparing pattern electroretinograms (PERG) and visual evoked potentials (PVEPs) amplitudes and peak-times recorded using a DLP laser projector, photometrically and spatially matched to existing plasma VDUs at our institution (Pioneer Electronics Corporation, PDP422MXE).The Viewsonic DLP laser projector was capable of high luminance levels (0-587.5 cd/mThe DLP laser projector tested in this study is a viable and practical replacement VDU for clinical electrophysiology tests of vision. The device is easily capable of meeting ISCEV standards, and showed PERG and PVEP amplitudes larger than existing systems despite photometric and spatial matching. The DLP laser projectors are capable of very large field sizes so are beneficial for paediatric testing or those wishing to examine large field responses. Importantly, it was observed that some devices may suffer input lag jitter, therefore, individual calibration and assessment of DLP projection systems is an important consideration before clinical implementation.

Purpose To describe the trans-occipital asymmetries of pattern and flash visual evoked potentials (VEPs), in an infant with MRI findings of unilateral optic nerve aplasia and hemi-chiasm dysplasia. Methods A child with suspected left cystic microphthalmia, left microcornea, left unilateral optic nerve aplasia, and hemi-chiasm underwent a multi-channel VEP assessment with pattern reversal, pattern onset, and flash stimulation at the age of 16 weeks. Results There was no VEP evidence of any post-retinal visual pathway activation from left eye with optic nerve aplasia. The VEP trans-occipital distribution from the functional right eye was skewed markedly across the midline, in keeping with significant misrouting of optic nerve fibres at the chiasm. This was supported by the anatomical trajectory of the optic chiasm and tracts seen on MRI. Conclusion This infant has chiasmal misrouting in association with unilateral optic nerve aplasia and unilateral microphthalmos. Chiasmal misrouting has not been found in patients with microphthalmos or anophthalmos, but has been reported after early eye loss in animal models. Our findings contribute to our understanding of the discrepancy between the visual pathway physiology of human unilateral microphthalmia and animal models.

Visual evoked potentials (VEPs) assess the function of the visual pathway from the retina to the primary visual cortex. There is much evidence that monocular pattern-reversal and flash VEPs can distinguish dysfunction due to chiasmal and post-chiasmal afferent pathway lesions. There is less evidence about the use of pattern-onset/OFFset VEPs to identify post-chiasmic dysfunction. We present nine patients with a range of visual pathway defects that caused dense hemianopic field defects. These patients had pattern onset–OFFset VEPs recorded from an array of occipital electrodes referred to a mid-frontal electrode to checks that appeared for 230 ms and disappeared for 300 ms into a background of mean luminance, in a stimulus field of 30°. We found pattern-onset VEP components lateralise to occipital electrodes overlaying the functional hemisphere, whereas pattern-OFFset VEP components demonstrate the paradoxical lateralisation phenomenon, described in reversal VEPs, and are maximal over the contralateral occiput. Our findings show how extending the recording time window to include an OFFset VEP facilitates identification of hemianopic visual field defects. We advocate the pattern-onset/OFFset VEP in the assessment of patients with hemianopia, having particular value for patients who are otherwise unable to perform more demanding half-field electrophysiology, imaging or psychophysical testing.

Proteus syndrome arises as a result of a post-zygotic mosaic activating mutation in the AKT1 oncogene, causing a disproportionate overgrowth of affected tissues. A small number of ocular complications have been reported. We present the unique findings in a patient who had molecular confirmation of AKT1 mosaicism alongside fulfilling the clinical criteria for Proteus syndrome. Pattern electroretinography, visual evoked potentials and multifocal electroretinography testing were performed alongside detailed retinal imaging and clinical examination to detail the ophthalmic characteristics. Electrophysiological findings characterised unilateral macular dysfunction alongside sector retinal dysfunction of the right eye. This was demonstrated through optical coherence tomography and ultra-wide-field imaging to be associated with a misaligned foveal morphology and sector retinal dysfunction extending into the temporal retina. We propose this patient has asymmetric foveal development and concomitant sector retinal dysfunction as the result of the mosaic AKT1 mutation, either through disruption in the retinal PI3K-AKT1 signalling pathway or through mechanical distortion of ocular growth, resulting in disproportionate inner retinal development. The findings expand the ocular phenotype of Proteus syndrome and encourage early assessment to identify any incipient ocular abnormalities.

Grouped congenital hypertrophy of the retinal pigment epithelium is a conspicuous ocular anomaly wherein highly pigmented, demarcated but flat retinal lesions arise from the retinal pigment epithelium. These lesions ("bear tracks") typically increase in size as they approach the retinal periphery. The discovery of pigmentary lesions in a young infant with a poor red reflex warrants urgent ophthalmological and electrodiagnostic review to exclude serious diagnoses, including an early-onset severe retinal dystrophy. We present the case of a 2-month-old boy with marked bear-tracks over the entirety of each retina, but with normal electrodiagnostic findings, genetics, and visual behavior.

IntroductionRaised intracranial pressure (rICP) can be a consequence of a variety of neurological disorders. A significant complication of rICP is visual impairment, due to retinal ganglion cell (RGC) dysfunction. In children, subjective measurements to monitor this, such as visual field examination, are challenging. Therefore, objective measurements offer promising alternatives for monitoring these effects. The photopic negative response (PhNR) is a component of the flash electroretinogram produced by RGCs; the cells directly affected in rICP-related vision loss. This project aims to assess the clinical feasibility and diagnostic efficacy of the PhNR in detecting and monitoring paediatric rICP.Methods and analysisSection 1 is a cross-sectional study; group 1 young persons with disorders associated with rICP and a comparator group 2 of age-matched children without rICP. Both groups will undergo a PhNR recording alongside a series of structural and functional ophthalmic investigations, with the rICP group also having measurement of intracranial pressure.Section 2 is a longitudinal study of the relationship between the PhNR and directly recorded intracranial pressure measurements, through repeated measures. PhNR amplitudes and peak times will be assessed against optical coherence tomography parameters, mean deviation of visual fields, other electrophysiology and ICP measurement through regression analyses.Group differences between PhNR measurements in the rICP and control groups will be performed to determine clinically relevant cut-off values and calculation of diagnostic accuracy. Longitudinal analysis will assess PhNR amplitude against ICP measurements through regression analysis. Feasibility and efficacy will be measured through acceptability, practicality and sensitivity outcomes.Ethics and disseminationFavourable opinion from a research ethics committee has been received and the study approved by Manchester Metropolitan University, the Health Research Authority and the Great Ormond Street Institute of Child Health (GOS-ICH) Research and Development office. This project is being undertaken as a doctoral award (ORM) with findings written for academic thesis submission, peer-reviewed journal and conference publications.

To assess the diagnostic accuracy and agreement between a paediatric electroretinography protocol used at Great Ormond Street Hospital (GOSH-ERG) and the 'gold standard' international protocol (ISCEV-ERG) in health and disease.Patient databases between 2010 and 2020 were screened to identify children with an ISCEV-ERG recorded within four years of a GOSH-ERG. Electroretinogram (ERG) component peak times and amplitudes were re-measured, and data were analysed in terms of absolute abnormality and proportional deviation from respective reference ranges. Abnormality was defined by the retinal system affected and by individual ERG a- and b-wave component analysis.A total of 59 patients were included: 38 patients had retinal disease defined by an abnormal ISCEV-ERG and 21 had normal ISCEV-ERGs. When absolute abnormality was defined by combined retinal systems, the GOSH-ERG showed an excellent overall sensitivity of 95% (accuracy 86%). Individual retinal systems showed good-excellent sensitivity (67%-100%) and specificity (68%-97%). Electroretinogram (ERG) component sensitivities ranged between 60% and 97% and specificities between 79% and 97% dependent upon the protocol step. The proportional relationship appeared mostly linear between protocols. Electroretinogram (ERG) morphology was comparable for both protocols in a range of retinal diseases including those with pathognomonic ERGs.We demonstrate the high diagnostic accuracy of a paediatric ERG protocol (GOSH-ERG) relative to ISCEV standard ERGs. The close proportional deviation and similar waveform morphology indicate ERGs from each protocol are similarly affected in disease. This encourages the use of the GOSH-ERG protocol in the screening, diagnosis and monitoring of retinal disease in children who are unable to comply with the rigorous ISCEV-ERG protocol.

To assess the diagnostic accuracy of fundoscopy and visual evoked potentials (VEPs) in detecting intracranial hypertension (IH) in patients with craniosynostosis undergoing spring-assisted posterior vault expansion (sPVE).Children with craniosynostosis undergoing sPVE and 48-hour intracranial pressure (ICP) monitoring were included in this single-centre, retrospective, diagnostic accuracy study. Data for ICP, fundoscopy and VEPs were analysed. Primary outcome measures were papilloedema on fundoscopy, VEP assessments and IH, defined as mean ICP 20 mmHg. Diagnostic indices were calculated for fundoscopy and VEPs against IH. Secondary outcome measures included final visual outcomes.Fundoscopic examinations were available for 35 children and isolated VEPs for 30 children, 22 of whom had at least three serial VEPs. Sensitivity was 32.1% for fundoscopy (95% confidence intervals [CI]: 15.9-52.4) and 58.3% for isolated VEPs (95% CI 36.6-77.9). Specificity for IH was 100% for fundoscopy (95% CI: 59.0-100) and 83.3% for isolated VEPs (95% CI: 35.9-99.6). Where longitudinal deterioration was suspected from some prVEPs but not corroborated by all, sensitivity increased to 70.6% (95% CI: 44.0-89.7), while specificity decreased to 60% (95% CI: 14.7-94.7). Where longitudinal deterioration was clinically significant, sensitivity decreased to 47.1% (23.0-72.2) and specificity increased to 100% (47.8-100). Median final BCVA was 0.24 logMAR (n = 36). UK driving standard BCVA was achieved by 26 patients (72.2%), defined as ≥0.30 logMAR in the better eye.Papilloedema present on fundoscopy reliably indicated IH, but its absence did not exclude IH. VEP testing boosted sensitivity at the expense of specificity, depending on method of analysis.

Craniopagus conjoined twins are extraordinarily rare and present unique challenges to the multidisciplinary team. There is a paucity of literature on optimizing neuro-ophthalmologic evaluation in craniopagus twins. Herein, we present our enhanced neuro-ophthalmologic evaluation and management in 17-month-old male craniopagus twins, uniquely using handheld optical coherence tomography (OCT) plus portable slit-lamp biomicroscopy, indirect ophthalmoscopy and modified forced-choice preferential looking assessment. Staged surgical separation was supported by enhanced neuro-ophthalmologic evaluation, detailed radiology, three-dimensional printing and virtual reality simulation. This represents the fourth separation of craniopagus twins by our unit.

Our aim is to elaborate the clinical significance of giant amplitude pattern reversal visual evoked potentials (VEPs) in children. ‘Giant’ amplitude VEPs exceed the upper 97.5th centile, 90% CI for age. We scrutinised 2750 pattern VEPs recorded to international standards between Jan 2015 and 2017 from children aged 16 years and under, attending a specialist children's hospital. Twenty seven children, median age 6yrs, (range 1–16 yrs), were identified with giant VEPs (P100 amplitude range 65–163 μV). Most, 22/27 (81%), had conditions associated with a risk of raised ICP. Sixteen of these twenty two children had craniosynostosis; six multi-sutural and eight single suture disease. Others had Idiopathic Intracranial Hypertension, arachnoid cyst, NF1 with shunted hydrocephalus, chronic infantile neurological cutaneous and articular (CINCA) syndrome, nephrotic cystinosis and obstructive sleep apnoea. Five children presented with a range of conditions, some associated with seizures some symptomatic, but as yet undiagnosed. Frequent structural associations were optical coherence tomography measures of optic disc maximum anterior axial horizontal retinal thickness projection >160 μm and neuro-radiological findings of CSF effacement and copper beaten appearance. Ultrasonography measures of optic nerve sheath diameters varied, but in one child took 2 years to resolve after treatment for raised ICP. Optic disc gradings by fundoscopy were mostly normal, as were visual acuities. Raised ICP was confirmed by gold standard ICP bolt measurements in five of seven children tested. These data suggest that rICP should be considered if a child has sustained giant amplitude VEPs at normal latency.

Proteus syndrome arises as a result of a post-zygotic mosaic activating mutation in the AKT1 oncogene, causing a disproportionate overgrowth of affected tissues. A small number of ocular complications have been reported. We present the unique findings in a patient who had molecular confirmation of AKT1 mosaicism alongside fulfilling the clinical criteria for Proteus syndrome.Pattern electroretinography, visual evoked potentials and multifocal electroretinography testing were performed alongside detailed retinal imaging and clinical examination to detail the ophthalmic characteristics.Electrophysiological findings characterised unilateral macular dysfunction alongside sector retinal dysfunction of the right eye. This was demonstrated through optical coherence tomography and ultra-wide-field imaging to be associated with a misaligned foveal morphology and sector retinal dysfunction extending into the temporal retina.We propose this patient has asymmetric foveal development and concomitant sector retinal dysfunction as the result of the mosaic AKT1 mutation, either through disruption in the retinal PI3K-AKT1 signalling pathway or through mechanical distortion of ocular growth, resulting in disproportionate inner retinal development. The findings expand the ocular phenotype of Proteus syndrome and encourage early assessment to identify any incipient ocular abnormalities.