The influence of congenital corneal opacity on ERGs obtained using an abbreviated protocol.

BACKGROUND: Visual electrophysiology may be used to assess visual potential in infants with congenital corneal opacities (CCO). It is essential to recognize confounding effects from these opacities on the flash electroretinogram (ERG). METHODS: ERGs were recorded in awake children employing skin electrodes placed at the lower eyelid crease, both referred to a midfrontal electrode (Fz). A hand-held stimulator was used to present a mixed rod-cone and a dim white stimulus. Recordings were carried out before and after penetrating keratoplasty (PK), when performed. RESULTS: Five infants under the age of 12 months with visually significant CCO were evaluated. In all cases, initial ERGs employing the mixed rod-cone stimulus showed well-defined a-wave with reduced amplitude b-wave. Reduction of stimulus intensity resulted in an increase in the b-wave and normalization of the b:a ratio from 1.1 (range 0.7 to 1.3) to 2.8 (range 1.5 to 4.3). In three cases who underwent PK, the postoperative ERGs recorded with a mixed rod-cone stimulus were normal in waveform shape with a mean b:a ratio of 2.0 (range 1.7 to 3.0). CONCLUSION: Selective reduction of the scotopic bright flash ERG b-wave is typically caused by retinal dysfunction that is post-phototransduction or inner retinal. In infants with CCO, scotopic ERGs to bright flashes can show a reduced b:a ratio that improves or normalizes either after PK or stimulus intensity reduction. The study highlights that media opacity can contribute to the generation of an ERG with reduced b-wave in the absence of inner retinal dysfunction.

Mapping degeneration of the visual system in long-term follow-up after childhood hemispherectomy - A series of four cases.

OBJECTIVE: Although hemidisconnection surgery may eliminate or reduce seizure activity in patients with epilepsy, there are visual, cognitive and motor deficits which affect patients' function post-operatively, with varying severity and according to pathology. Consequently, there is a need to map microstructural changes over long time periods and develop/apply methods that work with legacy data. METHODS: In this study, we applied the novel single shell 3-Tissue method to data from a cohort of 4 patients who were scanned 20-years following childhood hemidisconnection surgery and presented with variable clinical outcomes. We have successfully reconstructed tractography of the whole visual pathway from single shell diffusion data with reduced number of gradient directions. RESULTS: All patients presented with degeneration of the visual system characterised by low fractional anisotropy and high mean diffusivity. There were no apparent microstructural differences between both optic nerves that could explain the different level of visual function across patients. However, we provide evidence suggesting an association between the level of visual function and DTI metrics within the remaining components of the visual system, particularly the optic tract, of the contralateral hemisphere post-surgery. SIGNIFICANCE: We believe this study suggests that diffusion MRI can be used to monitor the integrity of the visual system following hemispherectomy and if extended to larger cohorts and a greater number of time-points, including pre-surgically, can provide a clearer picture of the natural history of visual system degeneration. This knowledge may in turn help to identify patients at greatest risk of poor visual outcomes that might benefit from rehabilitation therapies.

Giant pattern VEPs in children.

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.

An ERG and OCT study of neuronal ceroid lipofuscinosis CLN2 Battens retinopathy.

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.

What can visual electrophysiology tell about possible visual-field defects in paediatric patients.

Recognising a potential visual-field (VF) defect in paediatric patients might be challenging, especially in children before the age of 5 years and those with developmental delay or intellectual disability. Visual electrophysiological testing is an objective and non-invasive technique for evaluation of visual function in paediatric patients, which can characterise the location of dysfunction and differentiate between disorders of the retina, optic nerve and visual pathway. The recording of electroretinography (ERG) and visual-evoked potentials (VEP) is possible from early days of life and requires no subjective input from the patient. As the origins of ERG and VEP tests are known, the pattern of electrophysiological changes can provide information about the VF of a child unable to perform accurate perimetry. This review summarises previously published electrophysiological findings in several common types of VF defects that can be found in paediatric patients (generalised VF defect, peripheral VF loss, central scotoma, bi-temporal hemianopia, altitudinal VF defect, quadrantanopia and homonymous hemianopia). It also shares experience on using electrophysiological testing as additional functional evidence to other tests in the clinical challenge of diagnosing or excluding VF defects in complex paediatric patients. Each type of VF defect is illustrated with one or two clinical cases.

Enhanced neuro-ophthalmologic evaluation to support separation of craniopagus twins.

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.

Case report: Unilateral optic nerve aplasia and developmental hemi-chiasmal dysplasia with VEP misrouting.

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.

Pattern-onset and OFFset visual evoked potentials in the diagnosis of hemianopic field defects.

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.

Misaligned foveal morphology and sector retinal dysfunction in AKT1-mosaic Proteus syndrome.

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.

Microstructural Investigations of the Visual Pathways in Pediatric Epilepsy Neurosurgery: Insights From Multi-Shell Diffusion Magnetic Resonance Imaging.

BACKGROUND: Surgery is a key approach for achieving seizure freedom in children with focal onset epilepsy. However, the resection can affect or be in the vicinity of the optic radiations. Multi-shell diffusion MRI and tractography can better characterize tissue structure and provide guidance to help minimize surgical related deficits. Whilst in adults tractography has been used to demonstrate that damage to the optic radiations leads to postoperative visual field deficits, this approach has yet to be properly explored in children. OBJECTIVE: To demonstrate the capabilities of multi-shell diffusion MRI and tractography in characterizing microstructural changes in children with epilepsy pre- and post-surgery affecting the occipital, parietal or temporal lobes. METHODS: Diffusion Tensor Imaging and the Spherical Mean Technique were used to investigate the microstructure of the optic radiations. Furthermore, tractography was used to evaluate whether pre-surgical reconstructions of the optic radiations overlap with the resection margin as measured using anatomical post-surgical T1-weighted MRI. RESULTS: Increased diffusivity in patients compared to controls at baseline was observed with evidence of decreased diffusivity, anisotropy, and neurite orientation distribution in contralateral hemisphere after surgery. Pre-surgical optic radiation tractography overlapped with post-surgical resection margins in 20/43 (46%) children, and where visual data was available before and after surgery, the presence of overlap indicated a visual field deficit. CONCLUSION: This is the first report in a pediatric series which highlights the relevance of tractography for future pre-surgical evaluation in children undergoing epilepsy surgery and the usefulness of multi-shell diffusion MRI to characterize brain microstructure in these patients.

Altered visual population receptive fields in human albinism.

Albinism is a congenital disorder where misrouting of the optic nerves at the chiasm gives rise to abnormal visual field representations in occipital cortex. In typical human development, the left occipital cortex receives retinal input predominantly from the right visual field, and vice-versa. In albinism, there is a more complete decussation of optic nerve fibers at the chiasm, resulting in partial representation of the temporal hemiretina (ipsilateral visual field) in the contralateral hemisphere. In this study, we characterize the receptive field properties for these abnormal representations by conducting detailed fMRI population receptive field mapping in a rare subset of participants with albinism and no ocular nystagmus. We find a nasal bias for receptive field positions in the abnormal temporal hemiretina representation. In addition, by modelling responses to bilateral visual field stimulation in the overlap zone, we found evidence in favor of discrete unilateral receptive fields, suggesting a conservative pattern of spatial selectivity in the presence of abnormal retinal input.

Occipital Petalia and Albinism: A Study of Interhemispheric VEP Asymmetries in Albinism with No Nystagmus.

The purpose of this study was to assess chiasmal misrouting in a cohort of children with albinism with no nystagmus using hemifield visual evoked potentials (VEP) measures. METHODS: Monocular VEPs were recorded and analyzed from three electrodes (O1, Oz, and O2 referred to Fz) from 16 children with albinism without nystagmus. Pattern reversal (full field and hemifield stimulation), full field pattern appearance and flash stimuli were used to evoke VEPs for each eye. RESULTS: The amplitude of the pattern reversal VEPs to stimulation of the hemifield corresponding to the crossing pathways were as expected significantly larger than those to the non-crossing in each eye ((right eye p = 0.000004), (left eye p = 0.001)). Pattern reversal VEPs recorded from the left hemisphere were also larger than those from the right and most evident when comparing the crossing pathways of each eye (p = 0.004). CONCLUSIONS: This study has demonstrated electrophysiological differences in visual pathway function of the left and right hemisphere in subjects with albinism like that previously described in controls. Nasal field stimulation activated crossing and non-crossing pathways in patients with albinism and as a result, nasal hemifield VEPs in albinism are less lateralized compared to what is found in normal subjects.

ERGs on the brain: the benefits of simultaneous flash retinal and cortical responses in paediatric cerebral visual impairment.

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.

Trans-synaptic Retrograde Degeneration Following Hemispherectomy in Childhood.

Trans-synaptic retrograde degeneration (TRD) in the human visual system has been established. However there are few studies demonstrating macular thinning of the Retinal Ganglion cell Layer and/or Inner Plexiform layer (RGCL-IPL), corresponding to an acquired homonymous hemianopia. We report a 17 year old with a homonymous hemianopia, secondary to a hemispherectomy for intractable epilepsy. Three years following hemispherectomy, Optical Coherence Tomography (OCT) revealed evidence of TRD, corresponding to his complete homonymous hemianopia. Macular maps of the RGCL-IPL thickness provides useful additional information to measurements of optic nerve Retinal Nerve Fibre Layer Thickness (RNFL) in identifying TRD in acquired homonymous hemianopia.

Visual Function 20 Years After Childhood Hemispherectomy for Intractable Epilepsy.

PURPOSE: To investigate visual function in adults post hemispherectomy in childhood. DESIGN: Noncomparative case series. METHODS: All participants underwent visual acuity, binocular function, visual field, optical coherence tomography (OCT) of the retinal nerve fiber layer (RNFL), and monocular pattern reversal visually evoked potentials (prVEP). PARTICIPANTS: Six adults who had a hemispherectomy in childhood (median 21.5 years postoperative). MAIN OUTCOME MEASURES: Comparison was made of visual acuity, visual field height, global RNFL thickness, and prVEP amplitude evoked by full- and half-field stimulation. Comparison of the eye ipsilateral to the side of surgery to the contralateral eye was achieved employing paired t tests to the visual function measures. RESULTS: All participants had homonymous hemianopia. The residual seeing visual field was constricted in all cases when compared with normative data despite crossing the midline into the blind hemifield in 11 of 12 eyes. This observation was supported by prVEP to stimuli presented in the blind half field. The height of the visual field was smaller in the eye contralateral to the side of surgery compared with the ipsilateral side (P = .047). Visual acuity and RNFL thickness also showed greater diminution in the contralateral eye (P = .040 and P = .0004). Divergent strabismus was found in 4 participants with greater field loss. CONCLUSIONS: Adults post hemispherectomy in childhood may have better visual function in the eye ipsilateral to the side of the hemispherectomy compared with the contralateral eye. Possible mechanisms of the interocular difference are discussed. Though visual fields and prVEP responses demonstrate evidence of reorganization into the blind half field, they also reveal significant unexpected constriction of the functional field.

Multichannel visual evoked potentials in the assessment of visual pathways in children with marked brain abnormalities.

PURPOSE: To demonstrate how multichannel visual evoked potentials (VEPs) can provide quantitative measures of visual function in children with marked cortical anatomy abnormalities. METHODS: Four children with marked brain pathology (2 holoprosencephaly, 2 giant interhemispheric cysts with hydrocephalus) underwent pattern reversal and flash VEP recordings from 16 equally distributed electrodes. Voltage maps of the major VEP components were constructed, and their distributions were compared to the magnetic resonance imaging (MRI) findings. RESULTS: No reproducible responses were evident in 1 case, and responses were present, but, as expected based on the MRI finding, not over the occipital electrodes in 3 cases. Thus, the standard clinical VEP electrode placement would not have detected responses. The distribution of responses during monocular testing obtained in 2 cases suggested normal decussation of the visual pathways at the chiasm, and voltage mapping indicated which part of the abnormally positioned brain tissue is functional visual cortex. CONCLUSIONS: In children with markedly abnormal brain anatomy, multichannel VEP recordings can provide quantifiable measures of visual pathway function detected in atypical locations. VEPs provide a quantifiable measure of visual function that could be used to assist in determining visual acuity levels, and offered a baseline for monitoring in the context of raised intracranial pressure. These recordings were also able to identify functional anatomical structures that were not apparent on MRI. In a clinical setting, the use of additional recordings from nonstandard electrode placement based on the MRI findings is suggested.

A case of internal ophthalmoplegia associated with varicella zoster.

The authors report a case of internal ophthalmoplegia in a 5-year-old boy presenting after primary varicella infection. This is an uncommon and mostly irreversible ocular manifestation after chickenpox. The internal ophthalmoplegia showed a potential mild improvement with oral acyclovir. Consideration should be given to starting treatment on presentation in such cases.