ABSTRACT
Biallelic variants in SUMF1 are associated with multiple sulfatase deficiency (MSD), a rare lysosomal storage disorder typically diagnosed in early infancy or childhood, marked by severe neurodegeneration and early mortality. We present clinical and molecular characterisation of three unrelated patients aged 13 to 58 years with milder clinical manifestations due to SUMF1 disease variants, including two adult patients presenting with apparent non-syndromic retinal dystrophy. Whole genome sequencing identified biallelic SUMF1 variants in all three patients; Patient 1 homozygous for a complex allele c.[290G>T;293T>A]; p.[(Gly97Val);(Val98Glu)], Patient 2 homozygous for c.866A>G; p.(Tyr289Cys), and Patient 3 compound heterozygous for c.726-1G>C and p.(Tyr289Cys). Electroretinography indicated a rod-cone dystrophy with additional possible inner retinal dysfunction in all three patients. Biochemical studies confirmed reduced, but not absent, sulfatase enzyme activity in the absence of extra-ocular disease (Patient 1) or only mild systemic disease (Patients 2, 3). These cases are suggestive that non-null SUMF1 genotypes can cause an attenuated clinical phenotype, including retinal dystrophy without systemic complications, in adulthood.
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PURPOSE: Our aim was to explore the effect of ambient lighting on the pattern ERG (PERG). METHODS: We compared PERGs recorded in two conditions; room lights on and room lights off. PERGs from 21 adult participants were recorded from each eye to high contrast checks of 50' side width, reversing 3rps in a large (30°) and then standard (15°) field. This was performed first in lights-ON conditions, then 2 min after the room lights were switched off. A minimum of 2 averages of 300 trials were acquired for each condition. A subset of 10 participants had PERGs recorded to a 50' check width with a range of stimulus contrasts (96-18%), also to a range of different check widths (100'-12') at high contrast in both ambient lighting conditions in a 30° field. RESULTS: The lights-ON P50 median peak time (PT) was 3 ms earlier than the lights-OFF P50 from the 30° field (range 0-5 ms) and 15° field (range 0-6 ms). The earlier lights-ON P50 PT was evident at different stimulus contrasts, even after accounting for stimulus contrast reductions associated with stray ambient lighting in lights-ON conditions. Lights-OFF and lights-ON P50 PT were similar to different check widths; the lights-OFF P50 PT to a 50' check width matched the lights-ON P50 PT to a 25' check width. CONCLUSION: PERG P50 PT in lights-ON ambient light conditions can be earlier than in lights-OFF ambient light conditions. The difference in P50 PT with ambient light may reflect alterations in spatial sensitivity associated with retinal adaptation. These results emphasise the clinical importance of consistent ambient lighting for PERG recording and calibration.
ABSTRACT
The pattern-reversal visual evoked potential (prVEP) is an established routine clinical test. Its objectivity is particularly valuable for assessing visual pathway function in children. International standards specify at a minimum that an active electrode is placed on the occiput at Oz, but we find an additional inferior electrode at the inion (Iz) provides larger and more sensitive prVEPs in young persons. This study assesses the significance and age-dependence of these observations. PrVEPs were recorded from 1487 patients considered ophthalmologically normal aged <20 years old, to a range of check widths including International Society for Clinical Electrophysiology of Vision (ISCEV) standard large (50') and small (12.5') check widths. P100 peak-time and amplitude from both electrode sites were analysed. A subset of 256 children were studied longitudinally by fitting logistic regression models including a random effect on subjects. PrVEPs were largest over the Iz electrode for the majority of infants and children. This transitioned with age to become equal or smaller at Oz as a function of check width. For ISCEV standard large and small check widths, transition periods were â¼8 and â¼12 years of age, respectively. We estimated abnormal result classifications of 3.7% with use of an Oz electrode alone, which decreases to 0.0-0.5% when adding or using an Iz electrode. The inferior dominance of prVEP topography in children may be explained by age-related anatomical changes altering the cortical dipole, combined with physiological maturation of the neural generators of the prVEP. We recommend the Iz electrode is used routinely in recording of prVEPs in children. KEY POINTS: Pattern visual evoked potentials (PVEPs) are an established clinical test which provide objective assessment of visual pathway function. These are particularly valuable in providing objective information of vision in children. International standards specify the active recording electrode should be placed at the mid-occiput (Oz), but we find that pattern-reversal visual evoked potential amplitudes are larger for a lower placed electrode (Iz) in young persons. This was assessed in 1487 patients who had simultaneous PVEP recording at both electrode positions, and it was found that the majority of PVEPs in children were larger over the Iz electrode. The developmental differences in PVEP distribution transitioned to be equal between Iz and Oz with increasing age as a function of check width, at â¼8 and â¼12 years old for large and small check widths, respectively. These differences will improve diagnostic accuracy of paediatric PVEPs. We hypothesise these changes reflect developmental anatomical and neurophysiological changes altering the PVEP dipole.
Subject(s)
Evoked Potentials, Visual , Infant , Humans , Child , Young Adult , Adult , Reaction Time/physiologyABSTRACT
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 = < 0.05). 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.
Subject(s)
Electroretinography , Evoked Potentials, Visual , Humans , Child , Vision, Ocular , Light , ElectrophysiologyABSTRACT
PURPOSE: To report an unexpectedly asymmetric, progressive nutritional optic neuropathy associated with vitamin A deficient optic canal hyperostosis in a 15-year-old female with a long history of a restricted diet. METHODS: We performed comprehensive ophthalmic assessments in a fifteen-year-old female with a long history of restricted eating who presented with suspected nutritional optic neuropathy, predominantly affecting the right eye vision. RESULTS: A review of computerised tomography and magnetic resonance imaging revealed bilateral optic canal hyperostosis likely associated with vitamin A deficiency. Electrodiagnostic tests and optical coherence tomography provided structure-function evidence of bilateral retinal ganglion cell dysfunction and notably revealed severe loss of temporal fibres in the left eye which showed cecocentral scotoma but normal visual acuity. Although selective damage of the papillomacular bundle has been well-documented in nutritional and toxic optic neuropathies, compressive optic canal hyperostosis secondary to nutritional deficiency has been rarely reported. CONCLUSIONS: Nutritional deficiencies are increasing in high-income countries and may be linked to the rise of gastrointestinal disorders, strict vegan and vegetarian diets and avoidant restrictive food intake disorder (ARFID) associated with conditions such as depression and autism spectrum syndrome (ASD). Our findings highlight the value of electrodiagnostic testing alongside imaging in complex nutritional optic neuropathies to help monitor, guide treatment and preserve remaining sight in a child.
Subject(s)
Optic Nerve Diseases , Optic Neuritis , Female , Child , Humans , Adolescent , Optic Nerve Diseases/diagnosis , Optic Nerve Diseases/etiology , Electroretinography , Retinal Ganglion Cells/pathologyABSTRACT
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.
Subject(s)
Electroretinography , Evoked Potentials, Visual , Infant , Adolescent , Humans , Child , Male , Female , Healthy Volunteers , Bayes TheoremABSTRACT
AIM: To investigate whether pattern reversal visual evoked potentials (PRVEPs) could predict future visual acuity in infants with cerebral visual impairment (CVI). METHOD: Fifty-five children (27 males, 28 females) with severe CVI seen in the ophthalmology department of a specialist children's hospital were identified retrospectively. Behavioural visual acuity and visual evoked potentials (VEPs) at presentation (time 1, T1) were compared with final visual acuity at late preschool/early school age (time 2, T2). Predictors of visual acuity at T2 were identified using univariate and multivariate logistic and linear regression analysis. RESULTS: Median age was 14 months at T1 (range: 6-44mo) and 63 months at T2 (range: 29-150mo). The presence of a PRVEP produced by a check width of 50' (minutes of arc) or smaller (T1) predicted (p=0.05) the presence of measurable preferential looking acuity at T2. The presence of PRVEP to check widths of 25' or smaller (T1) predicted (p=0.02) better preferential looking acuity (logMAR-equivalent) scores at T2. The latter association was independent of presenting acuity at T1. INTERPRETATION: The presence of PRVEPs to check widths of 50' and 25' in infancy provided useful information. VEPs in young children with CVI may have prognostic value regarding future acuity.
Subject(s)
Evoked Potentials, Visual , Vision Disorders , Child , Child, Preschool , Female , Humans , Infant , Male , Prognosis , Retrospective Studies , Vision Disorders/diagnosis , Vision Disorders/etiology , Visual AcuityABSTRACT
BACKGROUND: 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. METHODS: 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°. RESULTS: 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. CONCLUSION: 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.
Subject(s)
Evoked Potentials, Visual , Visual Cortex , Electroretinography , Hemianopsia/diagnosis , Hemianopsia/etiology , Humans , Pattern Recognition, Visual , Visual PathwaysABSTRACT
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.
Subject(s)
Optic Chiasm , Optic Nerve Diseases , Electroretinography , Evoked Potentials, Visual , Humans , Infant , Optic Chiasm/diagnostic imaging , Optic Nerve/diagnostic imaging , Optic Nerve Diseases/diagnosisABSTRACT
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.
Subject(s)
Amblyopia , Evoked Potentials, Visual , Adult , Child , Child, Preschool , Electroretinography , Humans , Infant , Vision, Ocular , Visual AcuityABSTRACT
PURPOSE: 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. METHODS: Pattern electroretinography, visual evoked potentials and multifocal electroretinography testing were performed alongside detailed retinal imaging and clinical examination to detail the ophthalmic characteristics. RESULTS: 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. CONCLUSION: 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.
Subject(s)
Proteus Syndrome , Electroretinography , Evoked Potentials, Visual , Fovea Centralis , Humans , Proteus Syndrome/diagnosis , Proteus Syndrome/genetics , Proto-Oncogene Proteins c-akt/genetics , Tomography, Optical CoherenceABSTRACT
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.
Subject(s)
Electroretinography , Evoked Potentials, Visual , Societies, Medical , Vision, Ocular , Visual AcuityABSTRACT
Inherited retinal disease is a common cause of visual impairment and represents a highly heterogeneous group of conditions. Here, we present findings from a cohort of 722 individuals with inherited retinal disease, who have had whole-genome sequencing (n = 605), whole-exome sequencing (n = 72), or both (n = 45) performed, as part of the NIHR-BioResource Rare Diseases research study. We identified pathogenic variants (single-nucleotide variants, indels, or structural variants) for 404/722 (56%) individuals. Whole-genome sequencing gives unprecedented power to detect three categories of pathogenic variants in particular: structural variants, variants in GC-rich regions, which have significantly improved coverage compared to whole-exome sequencing, and variants in non-coding regulatory regions. In addition to previously reported pathogenic regulatory variants, we have identified a previously unreported pathogenic intronic variant in CHM in two males with choroideremia. We have also identified 19 genes not previously known to be associated with inherited retinal disease, which harbor biallelic predicted protein-truncating variants in unsolved cases. Whole-genome sequencing is an increasingly important comprehensive method with which to investigate the genetic causes of inherited retinal disease.
Subject(s)
DNA Mutational Analysis , Genetic Variation/genetics , Genome, Human/genetics , Retinal Diseases/genetics , Adaptor Proteins, Signal Transducing/genetics , Alleles , Base Sequence , Choroideremia/genetics , Ethnicity/genetics , Exome/genetics , Female , Genes, Recessive/genetics , Humans , Introns/genetics , Male , Mutation , Rare Diseases/geneticsABSTRACT
AIM: Optic neuritis may be monophasic or occur as part of a relapsing demyelinating syndrome (RDS), such as multiple sclerosis, aquaporin-4 antibody (AQP4-Ab) neuromyelitis optical spectrum disorder (NMOSD), or myelin oligodendrocyte glycoprotein antibody (MOG-Ab)-associated disease. The aims of this study were to test whether clinical, electrophysiological, and microstructural parameters differ in multiple-sclerosis-associated optic neuritis (MS-ON) and antibody-associated optic neuritis (Ab-ON); to identify the clinical and paraclinical characteristics of children suffering worse long-term visual outcome of RDS-optic neuritis; and to explore the relationship between RNFL thickness and clinical parameters in RDS-optic neuritis. METHOD: Forty-two children with optic neuritis were retrospectively studied: 22 with multiple sclerosis (MS-ON) and 20 with antibody-associated demyelination (Ab-ON: MOG-Ab=16 and AQP4-Ab=4). Clinical and paraclinical features were analysed. RESULTS: Complete recovery of visual acuity was reported in 25 out of 42 children; eight out of 38 (21%) suffered moderate or severe visual impairment (logarithm of the minimum angle of resolution [logMAR]>0.5) in their worse eye, including four out of 38 who were blind (logMAR>1.3) in their worse eye (two with multiple sclerosis, two with AQP4-Ab NMOSD). None of the children with MOG-Ab were blind. Recurrence of optic neuritis was more common in the Ab-ON group than the MS-ON group (15 out of 20 vs seven out of 22, p=0.007). Retinal nerve fibre layer (RNFL) thickness at baseline inversely correlated with visual acuity at final follow-up (r=-0.41, p=0.008). There was no significant relationship between the number of episodes of optic neuritis and mean RNFL (r=-0.08, p=0.628), nor any significant relationship between the number of episodes of optic neuritis and visual impairment (r=0.03, p=0.794). INTERPRETATION: In children with RDS, long-term visual impairment inversely correlated with RNFL thickness, but not with the number of relapses of optic neuritis. Optical coherence tomography may have a role in assessing children with optic neuritis to monitor disease activity and inform treatment decisions. WHAT THIS PAPER ADDS: Long-term visual impairment is reported in 40% of children with a relapsing demyelinating syndrome following optic neuritis. Relapse of optic neuritis, occurring more frequently in the non-multiple-sclerosis group. Retinal nerve fibre layer thinning is associated with worse visual outcome. Optical coherence tomography can be used alongside clinical parameters as an objective measure of neuroretinal loss.
ABSTRACT
PURPOSE: To highlight the importance of simultaneous flash electroretinogram (ERG) and visual evoked potential (VEP) recording to differentiate a true flash VEP response from an artefact caused by the intrusion of the ERG on a mid-frontal reference electrode in cases of severe cerebral visual impairment (CVI). METHODS: We report an observational case series of four children with severe CVI who underwent simultaneous flash ERG and VEP recordings. Flash VEPs from Oz-Fz and lower lid skin ERGs referred to Fz were recorded simultaneously to Grass intensity setting 4 flash stimulation. RESULTS: In all cases, atypical, but reproducible VEPs were evident. Comparison of the timing and waveform of the VEPs and ERGs showed the occipital responses were inverted ERGs and no true flash VEP was evident. CONCLUSIONS: While ISCEV and neurophysiology standards do not require the simultaneous recording of the flash ERG with the VEP, these cases highlight the usefulness of this non-invasive technique particularly in suspected paediatric cerebral visual impairment to differentiate a true VEP from an artefact caused by ERG contamination.
Subject(s)
Brain Diseases/physiopathology , Electroretinography , Evoked Potentials, Visual/physiology , Photic Stimulation , Retina/physiology , Vision Disorders/physiopathology , Visual Cortex/physiology , Adolescent , Artifacts , Child , Child, Preschool , Female , Humans , Infant , Male , Retrospective StudiesABSTRACT
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.
Subject(s)
Dark Adaptation/physiology , Electrophysiology/standards , Electroretinography/methods , Photic Stimulation , Retinal Cone Photoreceptor Cells/physiology , Retinal Dystrophies/physiopathology , Adult , Child , Clinical Protocols/standards , Female , Humans , Male , Societies, Medical/organization & administration , Vitamin A DeficiencyABSTRACT
PURPOSE: Pattern onset VEPs do not always show distinct C1-C2-C3 peaks and troughs. Our purpose was to study changes in pattern onset VEP with age to determine when the illustrated ISCEV standard onset VEP waveform can be reliably recorded. METHODS: We recorded pattern onset VEPs from an Oz electrode referred to mid-frontal electrode according to ISCEV standards by presenting checks of 60' and 15' side length in a 15° field. Twenty-four adults aged 20-63 years participated. Amplitudes and latencies were collated. Pattern onset adult VEP shapes were compared to the waveform published in the ISCEV VEP standard and to paediatric pattern onset VEP waveforms recorded from 16 infants aged 7 months. RESULTS: The shape of the pattern onset VEP changed gradually with age. The C1-C2-C3 morphology of the ISCEV standard pattern onset VEP becomes apparent consistently after 40 years to 60' check stimulation. As age increases a negative trough, C2 is more frequently seen; however, the broad positive peak which characterises infant onset VEPs may still be recorded at 20 years. The group median measurements of onset VEPs to 60' were C1 7 µV@ 88 ms (range 67-110 ms), C2 9 µV@109 ms (range 89-158 ms) and C3 13 µV@121-246 ms. To smaller 15' checks, peak latencies were earlier and C2 became more obvious. The group median measures of onset VEPs to 15' were C1 2 µV@69 ms (55-108 ms), C2 10 µV@90 ms (77-145 ms) and C3 14 µV@122 ms (99-200 ms). CONCLUSION: The ISCEV standard onset VEP best describes the waveform configuration and latency of the onset VEP produced by 60' checks in adults of more than 40 years of age. The onset VEP waveform produced by 15' checks is distinguished by more prominent negative C2 and earlier C1 and C2 latencies.
Subject(s)
Electrophysiology/standards , Evoked Potentials, Visual/physiology , Ophthalmology/organization & administration , Adult , Aging/physiology , Cross-Sectional Studies , Female , Humans , Infant , Male , Middle Aged , Retrospective Studies , Societies, Medical/standards , Young AdultABSTRACT
BACKGROUND: The aim of the meta-analysis was to derive a range of mean normal clinical electrooculogram (EOG) values from a systematic review of published EOG studies that followed the guidelines of the ISCEV standard for clinical electro-oculography. METHODS: A systematic literature review was performed using four relevant databases limited to peer-reviewed articles in English between 1967 and February 2017. Studies reporting clinical EOG or FO normal values were included when the report used a standard 30° horizontal saccade, a retinal luminance of between 100 and 250 cd m-2, and had > 10 subjects in their normative values. The search identified 1145 articles after duplicates were removed with subsequent screening of the abstracts excluding a further 1098, resulting in 47 full-text articles that were then assessed by the author (PC) with a final nine articles meeting the inclusion criteria. An overall effect estimate using inverse variance-weighted meta-analysis was performed to estimate the mean values for the light peak/dark trough ratio (LP:DT ratio) (dilated and undilated), the time to the LP, the amplitude of the LP, dark trough (DT) and the fast oscillation (FO) peak-to-trough ratio from the included studies. RESULTS: The mean dilated LP:DT ratio was 2.35 (95% CI 2.28-2.42); undilated LP:DT ratio was 2.37 (95% CI 2.28-2.45); LP amplitude was 835 (95% CI 631-1039) µV and the mean time to the LP being 8.2 (95% CI 7.7-8.7) min. The mean DT amplitude was 358 (95% CI 292-424) µV, and the mean FO peak-to-trough ratio was 1.13 (95% CI 1.11-1.16). The results of the LP/DT ratio are drawn from studies with a mean ± standard deviation (SD) age of 34.08 ± 12.93 years for dilated and 33.65 ± 12.28 years for undilated LP/DT ratios. CONCLUSIONS: The meta-analysis of EOG studies has generated a reference range of normal mean values for clinicians to refer to when using the ISCEV clinical EOG. It provides a potential method to generate similar data sets from published normal values in related visual electrophysiology tests.
Subject(s)
Electrooculography/methods , Retina/physiology , Vision, Ocular/physiology , Humans , Reference Values , Retinal Pigment Epithelium/physiology , Vision Tests/methodsABSTRACT
PURPOSE: To explore early findings that individuals with autism spectrum disorder (ASD) have reduced scotopic ERG b-wave amplitudes. METHODS: Light-adapted (LA) and dark-adapted (DA) ERGs were produced by a range of flash strengths that included and extended the ISCEV standard from two subject groups: a high-functioning ASD group N = 11 and a Control group N = 15 for DA and N = 14 for LA ERGs who were matched for mean age and range. Flash strengths ranged from DA -4.0 to 2.3 log phot cd s m(-2) and LA -0.5 to 1.0 log phot cd s m(-2), and Naka-Rushton curves were fitted to DA b-wave amplitude over the first growth limb (-4.0 to -1.0 log phot cd s m(-2)). The derived parameters (V max, K m and n) were compared between groups. Scotopic 15-Hz flicker ERGs (14.93 Hz) were recorded to 10 flash strengths presented in ascending order from -3.0 to 0.5 log Td s to assess the slow and fast rod pathways, respectively. LA 30-Hz flicker ERGs, oscillatory potentials (OPs) and the responses to prolonged 120-ms ON-OFF stimuli were also recorded. RESULTS: The ISCEV LA b-wave amplitude produced by 0.5 log phot cd s m(-2) was lower in the ASD group (p < 0.001). Repeated measures ANOVA for the LA b-wave amplitude series forming the photopic hill was significantly (p = 0.01) different between groups. No group differences were observed for the distributions of the time to peaks of LA a-wave, b-wave or the photopic negative responses (phNR) (p > 0.08) to the single flash stimuli, but there was a significant difference in the distribution for the LA b-wave amplitudes (corrected p = 0.006). The prolonged 120-ms ON responses were smaller in the ASD group (corrected p = 0.003), but the OFF response amplitude (p > 0.6) and ON and OFF times to peaks (p > 0.4) were similar between groups. The LA OPs showed an earlier bifurcation of OP2 in the younger ASD participants; however, no other differences were apparent in the OPs or 30-Hz flicker waveforms. DA b-wave amplitudes fell below the control 5th centile of the controls for some individuals including four ASD participants (36 %) at the 1.5 log phot cd s m(-2) flash strength and two (18%) ASD participants at the lower -2 log phot cd s m(-2) flash strength. However, across the 13 flash strengths, there were no significant group differences for b-wave amplitude's growth (repeated measures ANOVA p = 0.83). Nor were there any significant differences between the groups for the Naka-Rushton parameters (p > 0.09). No group differences were observed in the 15-Hz scotopic flicker phase or amplitude (p > 0.1), DA ERG a-wave amplitude or time to peak (p > 26). The DA b-wave time to peak at 0.5 log phot cd s m(-2) was longer in the ASD group (p = 0.04). CONCLUSION: Under LA conditions, the b-wave is reduced across the ASD group, along with the ON response of the prolonged flash ERG. Some ASD individuals also show subnormal DA ERG b-wave amplitudes. These exploratory findings suggest there is altered cone-ON bipolar signalling in ASD.