Comparing paediatric optometric vision care in Canada over a 14-year period.

PURPOSE: In Canada, teaching in paediatric eye care has increased in the past decade both within the optometry curriculum and as continuing education to optometrists. Paediatric vision care guidelines have also been established by North American optometric associations. This study examined whether this exposure was associated with changes in paediatric eye care in Canada over a 14-year period. METHODS: Canadian optometrists were invited to participate in an anonymous 35-item survey in 2007 and 2021. The surveys sought to investigate optometrist's recommendations for first eye examinations, the number of paediatric patients seen in a typical week and preparedness to provide eye examinations to children. Response frequencies were determined for each survey item. RESULTS: Across Canada, 133/1000 (13.3%) and 261/~6419 (~4.1%) optometrists responded to the survey in 2007 and 2021, respectively. No significant difference was found in the number of years practicing, days per week in practice and total number of patients seen per week. The modal age optometrists recommended children be seen for their first eye examination changed from 3-4 years in 2007 (53%) to 6-12 months in 2021 (61%). In 2007, 87% of respondents provided eye examinations to children <2 years, increasing to 94% in 2021 (p = 0.02). Despite a reduction in the recommended age between the two survey years, the most frequent age children were seen for their first eye examination was 3-4 years (30% in both surveys) and the most common age seen in a typical week remained unchanged (4-6 years-56% 2007; 66% 2021). CONCLUSION: Although optometrists' willingness to provide paediatric eye care increased over the past 14 years, the number of children seen in a typical week did not change. Barriers to determine why more children are not being seen at an earlier age need to be investigated.

ISCEV guidelines for calibration and verification of stimuli and recording instruments (2023 update).

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.

Flicker electroretinogram in newborn infants.

PURPOSE: To develop and validate a flicker electroretinogram (ERG) protocol in term-born neonates as a potential tool for assessing preterm infants at risk of developing retinopathy of prematurity. METHODS: A custom flicker ERG protocol was developed for use with the hand-held RETeval® electrophysiology device. Feasibility of measuring flicker ERG through closed eyelids and without mydriasis was established in a pilot study enabling optimisation of the test protocol. Following this, healthy term-born neonates (gestational age 37-42 weeks) were recruited at the Neonatology clinic of the University Hospital Zurich. Flicker ERG recordings were performed using proprietary disposable skin electrodes during the first four days of life when the infants were sleeping. Flicker stimuli were presented at 28.3 Hz for a stimulus series at 3, 6, 12, 30, and 50 cd·s/m2, with two measurements at each stimulus level. Results were analysed offline. Flicker ERG peak times and amplitudes were derived from the averaged measurements per stimulus level for each subject. RESULTS: 28 term-born neonates were included in the analysis. All infants tolerated the testing procedure well. Flicker ERG recording was achieved in all subjects with reproducible flicker ERG waveforms for 30 and 50 cd·s/m2 stimuli. Reproducible ERGs were recorded in the majority of infants for the weaker stimuli (with detectable ERGs in 20/28, 25/28, and 27/28 at 3, 6, and 12 cd·s/m2, respectively). Flicker ERG amplitudes increased with increasing stimulus strength, with peak times concurrently decreasing slightly. CONCLUSION: Flicker ERG recording is feasible and reliably recorded in sleeping neonates through closed eyelids using skin electrodes and without mydriasis. Flicker ERG amplitude decreases for lower luminance flicker but remains detectable for 3 cd·s/m2 flicker in the majority of healthy term-born neonates. These data provide a basis to study retinal function in premature infants using this protocol.

ISCEV Standard for full-field clinical electroretinography (2022 update).

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.

Modulation of binocular rivalry with rapid monocular visual stimulation.

Rapid visual stimulation can increase synaptic efficacy by repeated synaptic activation. This long-term potentiation-like (LTP-like) effect can induce increased excitability in the human visual cortex. To examine the effect of rapid visual stimulation on perception, we tested the hypothesis that rapid monocular visual stimulation would increase the dominance of the stimulated eye in a binocular rivalry task. Participants (n = 25) viewed orthogonal 0.5 cpd gratings presented in a dichoptic anaglyph to induce binocular rivalry. Rivalry dynamics (alternation rate, dominance, and piecemeal durations) were recorded before and after 2 min of rapid monocular stimulation (9 Hz flicker of one grating) or a binocular control condition (9 Hz alternation of the orthogonal gratings viewed binocularly). Rapid monocular stimulation did not affect alternation rates or piecemeal percept duration. Unexpectedly, the rivalry dominance of the stimulated eye was significantly reduced. A further experiment revealed that this effect could not be explained by monocular adaptation. Together, the results suggest that rapid monocular stimulation boosts dominance in the non-stimulated eye, possibly by activating homeostatic interocular gain control mechanisms.

Repeated measurements of ERGs and VEPs using chloral hydrate sedation and propofol anesthesia in young children.

PURPOSE: Sedation with chloral hydrate or anesthesia using propofol allow ocular examination and testing in young children, but these drugs may affect electrophysiologic recordings. We compared the flash and pattern ERGs and VEPs recorded with each drug in a cohort of young children enrolled in a prospective study of optic nerve hypoplasia (ONH) syndrome. METHODS: ERGs and VEPs to light-adapted, standard, full-field flashes, to standard and steady-state pattern-reversal (PR) were recorded with cycloplegia in 9 participants. Age range at the first session, with chloral hydrate was 8-23 mo; at the second session with propofol it was 20-29 mo. Examiners masked to the drug and clinical conditions measured the waveforms for longitudinal, paired comparisons between the sessions. RESULTS: Flash ERG amplitudes did not differ between sessions; peak times were longer at the second session (propofol) by clinically insignificant amounts (< 2 ms, p = 0.002). Standard PERGs had larger amplitudes and later peaks in the second session (propofol) than with chloral hydrate (P50 2.9 vs 4.7 µV, p = 0.016 and 43 vs 52 ms, p < 0.001; N95 4.0 vs 6.1 µV, p = 0.003 and 91 vs 98.5 ms p = 0.034.). These differences were present for those with an interval of  > 10 mo between sessions (n = 5, 10 eyes) but not for those with a shorter inter-test interval (< 8 mo, p > 0.05, n = 4). Magnitudes of the steady-state PERGs did not differ between tests but the waveforms had earlier peaks at the second test with propofol. Flash VEP waveforms were present in 10/18 eyes and showed 72% agreement for recordability between sessions. Standard pattern VEPs were recordable in only a few eyes in this cohort with ONH. CONCLUSIONS: Light-adapted flash ERG waveforms were generally similar with chloral hydrate and with propofol. Larger PERGs with later peaks, found in the second session (propofol) could reflect maturation of the PERG generators, as the differences found were associated with a greater age difference between the sessions, but we do not rule out that small differences in the waveforms may be drug-related. There are insufficient VEP data from these children with ONH to identify drug-related or maturational effects on VEPs.

VEP estimation of visual acuity: a systematic review.

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.

ISCEV extended protocol for VEP methods of estimation of visual acuity.

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.

ISCEV extended protocol for the stimulus-response series for light-adapted full-field ERG.

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.

Isoflurane and ketamine:xylazine differentially affect intraocular pressure-associated scotopic threshold responses in Sprague-Dawley rats.

PURPOSE: Amplitudes of electroretinograms (ERG) are enhanced during acute, moderate elevation of intraocular pressure (IOP) in rats anaesthetised with isoflurane. As anaesthetics alone are known to affect ERG amplitudes, the present study compares the effects of inhalant isoflurane and injected ketamine:xylazine on the scotopic threshold response (STR) in rats with moderate IOP elevation. METHODS: Isoflurane-anaesthetised (n = 9) and ketamine:xylazine-anaesthetised (n = 6) rats underwent acute unilateral IOP elevation using a vascular loop anterior to the equator of the right eye. STRs to a luminance series (subthreshold to -3.04 log scotopic cd s/m2) were recorded from each eye of Sprague-Dawley rats before, during, and after IOP elevation. RESULTS: Positive STR (pSTR) amplitudes for all conditions were significantly smaller (p = 0.0001) for isoflurane- than for ketamine:xylazine-anaesthetised rats. In addition, ketamine:xylazine was associated with a progressive increase in pSTR amplitudes over time (p = 0.0028). IOP elevation was associated with an increase in pSTR amplitude (both anaesthetics p < 0.0001). The absolute interocular differences in IOP-associated enhancement of pSTR amplitudes for ketamine:xylazine and isoflurane were similar (66.3 ± 35.5 vs. 54.2 ± 24.1 µV, respectively). However, the fold increase in amplitude during IOP elevation was significantly higher in the isoflurane- than in the ketamine:xylazine-anaesthetised rats (16.8 ± 29.7x vs. 2.1 ± 2.7x, respectively, p = 0.0004). CONCLUSIONS: The anaesthetics differentially affect the STRs in the rat model with markedly reduced amplitudes with isoflurane compared to ketamine:xylazine. However, the IOP-associated enhancement is of similar absolute magnitude for the two anaesthetics, suggesting that IOP stress and anaesthetic effects operate on separate retinal mechanisms.

Predictive value of N95 waveforms of pattern electroretinograms (PERGs) in children with optic nerve hypoplasia (ONH).

PURPOSE: As part of a long-term, prospective study of prenatal and clinical risk factors for optic nerve hypoplasia (ONH) at Children's Hospital Los Angeles, pattern ERGs (PERGs) were evaluated for prognostic value using an automated objective and robust analytical method. METHODS: Participants were 33 children with ophthalmoscopically diagnosed ONH [disc diameter-to-disc macula ratio (DD/DM) less than 0.35 in one or both eyes on fundus photographs]. Using cycloplegia and chloral hydrate sedation in one session before 26 months of age, we recorded PERGs to checkerboard reversal using five check sizes. Participants were followed with clinical and psychometric testing until 5 years of age. PERGs were analysed using automated robust statistics based on magnitude-squared coherence and bootstrapping optimized to objectively quantify PERG recovery in the challenging recordings encountered in young patients. PERG measures in the fixating or better-seeing eyes were compared with visual outcome data. RESULTS: PERG recording was complete to at least three check sizes in all eyes and to all five sizes in 79%. Probability of recording a PERG that is significantly different from noise varied with check size from 73% for the largest checks to 30% for the smallest checks (p = 0.002); smaller waveforms were associated with earlier implicit times. The presence of significant PERGs in infancy is associated with better visual outcomes; the strongest association with visual outcome was for the threshold check size with a significant N95 component (ρ = 0.398, p = 0.02). CONCLUSIONS: Automated statistically robust signal-processing techniques reliably and objectively detect PERGs in young children with ONH and show that congenital deficits of retinal ganglion cells are associated with diminished or non-detectable PERGs. The later negativity, N95, was the best indicator of visual prognosis and was most useful to identify those with good visual outcomes (≤0.4 LogMAR). Although PERGs reflect function of the inner layers of the central retina, they lack the specificity required to determine prognosis reliably in individual cases.

ISCEV standard for clinical visual evoked potentials: (2016 update).

Visual evoked potentials (VEPs) can provide important diagnostic information regarding the functional integrity of the visual system. This document updates the ISCEV standard for clinical VEP testing and supersedes the 2009 standard. The main changes in this revision are the acknowledgment that pattern stimuli can be produced using a variety of technologies with an emphasis on the need for manufacturers to ensure that there is no luminance change during pattern reversal or pattern onset/offset. The document is also edited to bring the VEP standard into closer harmony with other ISCEV standards. The ISCEV standard VEP is based on a subset of stimulus and recording conditions that provide core clinical information and can be performed by most clinical electrophysiology laboratories throughout the world. These are: (1) Pattern-reversal VEPs elicited by checkerboard stimuli with large 1 degree (°) and small 0.25° checks. (2) Pattern onset/offset VEPs elicited by checkerboard stimuli with large 1° and small 0.25° checks. (3) Flash VEPs elicited by a flash (brief luminance increment) which subtends a visual field of at least 20°. The ISCEV standard VEP protocols are defined for a single recording channel with a midline occipital active electrode. These protocols are intended for assessment of the eye and/or optic nerves anterior to the optic chiasm. Extended, multi-channel protocols are required to evaluate postchiasmal lesions.

ISCEV Standard for full-field clinical electroretinography (2015 update).

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.

Comparison of human expert and computer-automated systems using magnitude-squared coherence (MSC) and bootstrap distribution statistics for the interpretation of pattern electroretinograms (PERGs) in infants with optic nerve hypoplasia (ONH).

PURPOSE: Pattern electroretinograms (PERGs) have inherently low signal-to-noise ratios and can be difficult to detect when degraded by pathology or noise. We compare an objective system for automated PERG analysis with expert human interpretation in children with optic nerve hypoplasia (ONH) with PERGs ranging from clear to undetectable. METHODS: PERGs were recorded uniocularly with chloral hydrate sedation in children with ONH (aged 3.5-35 months). Stimuli were reversing checks of four sizes focused using an optical system incorporating the cycloplegic refraction. Forty PERG records were analysed; 20 selected at random and 20 from eyes with good vision (fellow eyes or eyes with mild ONH) from over 300 records. Two experts identified P50 and N95 of the PERGs after manually deleting trials with movement artefact, slow-wave EEG (4-8 Hz) or other noise from raw data for 150 check reversals. The automated system first identified present/not-present responses using a magnitude-squared coherence criterion and then, for responses confirmed as present, estimated the P50 and N95 cardinal positions as the turning points in local third-order polynomials fitted in the -3 dB bandwidth [0.25 … 45] Hz. Confidence limits were estimated from bootstrap re-sampling with replacement. The automated system uses an interactive Internet-available webpage tool (see http://clinengnhs.liv.ac.uk/esp_perg_1.htm). RESULTS: The automated system detected 28 PERG signals above the noise level (p ≤ 0.05 for H0). Good subjective quality ratings were indicative of significant PERGs; however, poor subjective quality did not necessarily predict non-significant signals. P50 and N95 implicit times showed good agreement between the two experts and between experts and the automated system. For the N95 amplitude measured to P50, the experts differed by an average of 13% consistent with differing interpretations of peaks within noise, while the automated amplitude measure was highly correlated with the expert measures but was proportionally larger. Trial-by-trial review of these data required approximately 6.5 h for each human expert, while automated data processing required <4 min, excluding overheads relating to data transfer. CONCLUSIONS: An automated computer system for PERG analysis, using a panel of signal processing and statistical techniques, provides objective present/not-present detection and cursor positioning with explicit confidence intervals. The system achieves, within an efficient and robust statistical framework, estimates of P50 and N95 amplitudes and implicit times similar to those of clinical experts.

Pathogenesis of X-linked RP3: insights from animal models.

Retinitis Pigmentosa (RP) is a genetically heterogeneous disorder characterized by rod and cone photoreceptor cell dysfunction. X-linked RP (XLRP) is one of the most severe forms of human retinal degeneration, as determined by age-of-set and progression, and accounts for six to 20 % of all RP cases. At least six XLRP loci have been identified, but RP3 is the major subtype of XLRP, accounting for 70 to 80 % of affected families. The RPGR gene is responsible for the RP3 form of XLRP and is mutated in 10-20 % of all RP patients. The pathogenesis of retinitis pigmentosa GTPase regulator (RPGR) mutant-causing RP is not clear, different animal models have been used to understand the pathogenesis of these diseases. In this brief review, we will summarize the functional characterization of RPGR and highlight recent studies in animal models, which will not only shed light on the disease mechanisms in XLRP but will also provide therapeutic strategies for RP treatment.

Flicker electroretinogram in preterm infants.

BACKGROUND: Infants born prematurely are at risk of developing retinopathy of prematurity, which is associated with abnormalities in retinal function as measured using electroretinography. The aim of this study was to record non-invasive flicker electroretinograms (ERGs) in preterm infants and compare function of moderate and very or extremely preterm infants. METHODS: In this non-randomized, cross-sectional study, 40 moderate preterm (gestational age (GA) 34 0/7 to 36 6/7 weeks, Group A) and 40 very or extremely preterm infants (GA ≤ 31 weeks, Group B) were recruited for flicker ERG recording through closed eyelids using the RETeval® device and skin electrodes. Group A was tested within the first week of life and Group B between 34th and 37th week postmenstrual age. Flicker stimuli were presented at 28.3 Hz with stimulus levels of 3, 6, 12, 30 and 50 cd•s/m2. Primary endpoints were peak time (ms) and amplitude (µV). RESULTS: Flicker ERGs were recordable in most infants with the highest proportion of reproducible ERGs at 30 cd•s/m2. Amplitudes increased with stronger flicker stimulation, while peak times did not differ significantly between stimulus levels nor groups. Amplitudes were significantly greater in Group B at the strongest stimulus level (Mann-Whitney-U-Test=198.00, Z = 4.097, p = <0.001). CONCLUSIONS: Feasibility of collecting flicker ERG data in most preterm infants was confirmed. We found no evidence of reduced retinal responses to flicker stimuli associated with extreme prematurity. Higher amplitudes in very and extremely preterm infants could indicate acceleration of retinal development following birth, triggered by visual stimulation.

Idiopathic, isolated fovea plana with bilateral off-centre multifocal ERGs.

BACKGROUND: The purpose of this paper is to report a case of idiopathic isolated fovea plana showing asymmetry in the multifocal electroretinogram (mfERG). METHODS: We carried out optical coherence tomography (OCT) imaging, macular pigment density measurement, genetic testing and electrophysiological testing with visual evoked potentials and mfERGs on a young, highly myopic female of Pakistani origin, who had good visual acuity and no nystagmus. RESULTS: OCT imaging revealed a complete absence of any foveal pit in either eye. Macular pigment density was normal and visual evoked potentials indicated normal chiasmal crossings, excluding albinism. Genetic testing revealed normal PAX6 coding data, excluding aniridia as a cause. mfERGs showed asymmetry consistent with off-centre fixation to the temporal side of the fovea in both eyes, but were otherwise normal. CONCLUSION: Lack of a foveal pit is a well-known finding in conditions such as oculocutaneous albinism and PAX6 gene-related aniridia. Isolated fovea plana is less common, and this case illustrates that the absence of a foveal pit does not necessarily result in a poor visual outcome. The finding of asymmetry in the mfERG in such a case is novel, and may indicate a functional adaptation to the structure of the fovea.