Pediatric oral fluorescein angiography: a retrospective review from a single institution.

PURPOSE: To describe our experience with locally developed evidence-based guidelines for oral fluorescein angiography (FA) for retinal imaging in children. METHODS: The medical records of consecutive pediatric patients (≤18 years of age) at University of Pittsburgh Medical Center Children's Hospital Eye Center who underwent oral FA between November 1, 2018, and April 1, 2022, were reviewed retrospectively. Adherence to or deviation from the guidelines was noted at the time of testing. RESULTS: A total of 55 patients aged 3-18 with 79 examinations were included. No patient was excluded from the retrospective case review because of lack of recorded data. The main indications for oral FA included uveitis, retinal vasculopathy, disk pathology, and retinal lesions. Three children had transient side effects, and 1 had delayed urticaria 4 hours after examination. No child had anaphylaxis. One patient had suboptimal imaging due to nonadherence to the guidelines-recommended fasting protocol. All other examinations (78/79), where guidelines were followed, provided images adequate for clinical decision making. CONCLUSIONS: Based on our experience, we recommend that oral FA be considered, especially in children where intravenous access is less well tolerated while awake. Informed consent that includes the possibility of delayed side effects is advisable.

Prognostic value of transient pattern visual evoked potentials in children with cerebral visual impairment.

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.

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.

Quantitative MRI demonstrates abnormalities of the third ventricle subventricular zone in neurofibromatosis type-1 and sporadic paediatric optic pathway glioma.

BACKGROUND: The subventricular zone of the third ventricle (TVZ) is a germinal stem cell niche, identified as the possible location of optic pathway glioma (OPG) cell origin. Paediatric OPGs are predominantly diagnosed as low-grade astrocytomas, which are either sporadic or are associated with neurofibromatosis type-1 (NF1). These tumours often cause a significant impairment to visual acuity (VA). Infiltrative/invasive tumour activity is associated with increased apparent diffusion coefficient (ADC) and cerebral blood flow (CBF). This study aimed to determine whether TVZ imaging features differed between sporadic-OPG, NF1-OPG and controls, and whether the ADC and CBF profile at the germinal stem cell niche (the TVZ) correlated with the primary outcome of VA. METHODS: ADC and CBF MRI data were acquired from 30 paediatric OPG patients (median age 6 years; range 8 months-17 years), along with VA measurements, during clinical surveillance of their tumour. Values for mean ADC and maximum CBF were measured at the TVZ, and normalized to normal-appearing grey matter. These values were compared between the two OPG groups and the healthy control subjects, and multivariate linear regression was used to test the linear association between these values and patient's VA. RESULTS: In the TVZ, normalized mean ADC was higher in NF1-associated OPG patients (N = 15), compared to both sporadic OPG patients (N = 15; p = 0.010) and healthy controls (N = 14; p < 0.001). In the same region, normalized maximum CBF was higher in sporadic OPG patients compared to both NF1-OPG patients (p = 0.016) and healthy controls (p < 0.001). In sporadic OPG patients only, normalized mean ADC in the TVZ was significantly correlated with visual acuity (R2 = 0.41, p = 0.019). No significant correlations were found between TVZ CBF and ADC values and visual acuity in the NF1-associated OPG patients. CONCLUSION: Quantitative MRI detects TVZ abnormalities in both sporadic and NF1-OPG patients, and identifies TVZ features that differentiate the two. TVZ features may be useful MRI markers of interest in future predictive studies involving sporadic OPG.

Clinical use of the Insight Inventory in cerebral visual impairment and the effectiveness of tailored habilitational strategies.

AIM: To investigate the utility of the Insight Inventory (a structured clinical inventory completed by caregivers) for assessment of children with cerebral visual impairment; and to investigate effectiveness of tailored habilitational strategies derived from the responses to the Insight Inventory. METHOD: Fifty-one eligible children (26 males, 25 females; mean age 9y 5mo, SD 3y, range 5-16y) were recruited from Great Ormond Street Hospital, London. They underwent baseline assessment including neuro-ophthalmological and neuropsychological evaluations, and parent- and child-reported ratings on a questionnaire-based measure of quality of life. Parents also completed the Insight Inventory. On the basis of responses to the Inventory, families received individualized habilitational strategies. Follow-up assessments 6 months later included repeating the Insight Inventory and quality of life questionnaires. RESULTS: Correlations were found between the Insight Inventory and the Wechsler Intelligence Scale for Children, Fourth Edition, the Beery-Buktenica Test of Visual-Motor Integration, and the Benton Facial Recognition Test, suggesting that the Insight Inventory is an effective tool to estimate visual-perceptual difficulties. At 6 months follow-up, caregiver reports indicated significant improvements in the quality of life of children below the age of 12 years. INTERPRETATION: The Insight Inventory is a simple questionnaire which covers practical aspects of cognitive visual function in everyday life. It provides in-depth information about the aspects that children struggle with. It can also guide programmes of individualized habilitation strategies, which may enhance the quality of life of younger children. WHAT THIS PAPER ADDS: Questionnaire scores demonstrate biologically plausible correlations with formal neuropsychological tests of visual function. After administration of matched practical habilitational strategies, younger children showed improvement in quality of life and functional vision scores.

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.

Serial, Visually-Evoked Potentials for the Assessment of Visual Function in Patients with Craniosynostosis.

This study aimed to evaluate the effect of craniofacial surgical intervention on the visual pathway's function by comparing pre- to post-operative patterned, visually-evoked potentials (pVEP). A retrospective review was conducted on craniosynostosis patients who had pre- and post-craniofacial surgery pVEP testing. The pVEP measured grade in terms of amplitude latency and morphology of the waveforms. The pre- and post-operative results were compared. The study identified 63 patients (mean age at preoperative pVEP of 16.9 months). Preoperatively, 33 patients (52.4%) had abnormal pVEP. Nine patients had evidence of intracranial hypertension, and of those, eight (88.9%) had abnormal pVEP. Within 6 months postoperatively, 24 of 33 patients (72.7%) with abnormal preoperative pVEP developed normal postoperative pVEP, while all 30 patients with normal preoperative VEP maintained their normal results postoperatively. Significant improvements in pVEP latency in patients with broad or delayed latency waveforms was evident for subjects with preoperative grades 2-4 (grade 2, p = 0.015; grade 3, p = 0.029; grade 4; p = 0.007), while significant postoperative increase in amplitude was significant for patients with abnormally low amplitude grade 3 and 5 waveforms (grade 3, p = 0.011; grade 5, p = 0.029). Serial pVEP testing represents a useful tool for the early detection of visual pathway dysfunction and follow up visual pathway function in craniosynostosis. Surgical intervention for craniosynostosis can result in the reversal of preoperative pVEP abnormalities seen in these patients, resulting in the normalization of the pVEP waveform, amplitude and latency, depending on the preoperative pVEP abnormality.

Serial Visual Evoked Potentials in Patients with Craniosynostosis and Invasive Intracranial Pressure Monitoring.

This study aimed to detect the ability of pattern visual evoked potentials to detect visual pathway dysfunction in a cohort of patients with craniosynostosis who also had invasive intracranial pressure measurement. A retrospective review was conducted on craniosynostosis patients who had invasive intracranial pressure measurement and at least one pattern visual evoked potentials test. Reversal pattern visual evoked potentials were performed with both eyes open. Thirteen patients met the inclusion criteria (mean age at intracranial pressure measurement, 5.7 years). Seven patients had raised intracranial pressure, and of these, five (71.4 percent) had abnormal or deteriorated pattern visual evoked potentials parameters on serial testing, whereas all patients (100 percent) with normal intracranial pressure had normal pattern visual evoked potentials amplitude and latency. Four of the five patients (80 percent) with raised intracranial pressure and abnormal pattern visual evoked potentials did not show evidence of papilledema. The mean latency in patients with raised intracranial pressure (118.7 msec) was longer than in those with normal intracranial pressure (108.1 msec), although it did not reach statistical significance (p = 0.09), whereas the mean amplitude in patients with raised intracranial pressure (12.4 µV) was significantly lower than in patients with normal intracranial pressure (23.3 µV) (p = 0.03). The authors' results showed that serial pattern visual evoked potentials testing was able to detect visual pathway dysfunction resulting from raised intracranial pressure in five of seven craniosynostosis patients, and of these five patients, 80 percent had no evidence of papilledema, demonstrating the utility of serial pattern visual evoked potentials in follow-up of the visual function in craniosynostosis patients. CLINICAL QUESTION/LEVEL OF EVIDENCE:: Diagnostic, II.

Visual electrodiagnostics and eye movement recording - World Society of Pediatric Ophthalmology and Strabismus (WSPOS) consensus statement.

Visual electrodiagnostics and eye movement recording are important additional clinical tools in evaluation, diagnosing and management of ophthalmic and neurological disorders. Due to their objectiveness and non-invasiveness they can play an important role in pediatric ophthalmology. The WSPOS (World Society of Pediatric Ophthalmology and Strabismus) consensus statement gives insight into basic principles and highlights the clinical application of both visual electrodiagnostic tests and eye movement recording.

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.

Leber Congenital Amaurosis Associated with Mutations in CEP290, Clinical Phenotype, and Natural History in Preparation for Trials of Novel Therapies.

PURPOSE: To investigate and describe in detail the demographics, functional and anatomic characteristics, and clinical course of Leber congenital amaurosis (LCA) associated with mutations in the CEP290 gene (LCA-CEP290) in a large cohort of adults and children. DESIGN: Retrospective case series. PARTICIPANTS: Patients with mutations in CEP290 identified at a single UK referral center. METHODS: Review of case notes and results of retinal imaging (color fundus photography, fundus autofluorescence [FAF] imaging, OCT), electrophysiologic assessment, and molecular genetic testing. MAIN OUTCOME MEASURES: Molecular genetic testing, clinical findings including visual acuity and retinal imaging, and electrophysiologic assessment. RESULTS: Forty patients with LCA-CEP290 were identified. The deep intronic mutation c.2991+1655 A>G was the most common disease-causing variant (23/40 patients) identified in the compound heterozygous state in 20 patients (50%) and homozygous in 2 patients (5%). Visual acuity (VA) varied from 6/9 to no perception of light, and only 2 of 12 patients with longitudinal VA data showed deterioration in VA in their better-seeing eye over time. A normal fundus was found at diagnosis in younger patients (mean age, 1.9 years), with older patients showing white flecks (mean age, 5.9 years) or pigmentary retinopathy (mean age, 21.7 years). Eleven of 12 patients (92%) with OCT imaging had preservation of foveal architecture. Ten of 12 patients (83%) with FAF imaging had a perifoveal hyperautofluorescent ring. Having 2 nonsense CEP290 mutations was associated with worse final VA and the presence of nonocular features. CONCLUSIONS: Detailed analysis of the clinical phenotype of LCA-CEP290 in a large cohort confirms that there is a window of opportunity in childhood for therapeutic intervention based on relative structural preservation in the central cone-rich retina in a significant proportion of patients, with the majority harboring the deep intronic variant potentially tractable to several planned gene editing approaches.

Early Onset Sixth-Nerve Palsy with Eccentric Fixation.

PURPOSE: To report four cases of early onset sixth-nerve palsy all of whom had eccentric fixation. METHODS: A retrospective case note review was undertaken of all cases presenting to the senior author's private and NHS practice with early onset sixth palsy between 2006 and 2012. As well as demographic information, details of ophthalmic, orthoptic, electrophysiological examinations, and radiological investigations that were extracted from the records. RESULTS: Four children with unilateral or asymmetric early onset sixth-nerve palsy were identified, of which three were congenital. All four had MRI and only one had a normal MRI. Age at presentation ranged from 14-42 months, but all four had marked esotropia and poor visual acuities in the worst affected eye with eccentric fixation, which became more easily or only noticeable after surgical correction. Three patients with congenital sixth-nerve palsy underwent vertical muscle transposition with Botulinum Toxin A (BTXA) to the ipsilateral medial rectus, and two of these patients also had Foster sutures to the transposed vertical muscles. The fourth patient had unilateral medial rectus recession and lateral rectus resection. The mean preoperative measurement was 55Δ ET (range 50-60Δ), and the mean postoperative measurement was 11Δ ET (range 16XT-25ET) at near, and 2Δ XT (range 15XT-14ET) at distance. CONCLUSIONS: We speculate that early onset paralytic strabismus due to congenital sixth-nerve palsy results in an inability to cross fixate which results in the development of eccentric fixation. Attempts to use reverse occlusion to negate the eccentric fixation failed. We therefore recommend early surgery for this condition to avoid this sequelae.

Reduction of severe visual loss and complications following intra-arterial chemotherapy (IAC) for refractory retinoblastoma.

BACKGROUND: Intra-arterial chemotherapy (IAC) for retinoblastoma has been documented as causing visual loss and ocular motility problems. A lack of safety data has precluded its acceptance in all centres. METHODS: Retrospective cohort study of patients with retinoblastoma from 2013 to 2015 who had a healthy foveola and relapsed following systemic chemotherapy. All required IAC. The correlation of complications with doses of melphalan +/- topotecan used and putative catheterisation complications was assessed. Ocular complications were determined using vision, macular (including pattern visual evoked potentials (PVEPs)), retinal electroretinograms (ERGs) and ocular motility functions. Efficacy (tumour control) was also assessed. RESULTS: All eyes had age appropriate doses of melphalan with five having additional doses of topotecan. Severe physiological reactions requiring adrenaline were seen in six patients during the catheterisation procedure. Difficulty was documented in accessing the ophthalmic artery in 7/27 catheterisations. The median/mean number of courses of chemotherapy was three. No child had severe visual loss as assessed by age appropriate tests (median follow-up 20.9 months, range 3.7-35.2 months). One child had nasal choroidal ischaemia and a sixth nerve palsy. Post-IAC PVEPs were performed in eight and reported as normal. All post-IAC ERGs were normal apart from one (total dose 20 mg melphalan 0.8 mg topotecan). Tumour control was achieved in six of nine cases. CONCLUSION: The proportion of visual and ocular motility complications may be reduced by providing age-adjusted doses of melphalan. Dose rather than complications from catheterisation is the most important risk factor for ocular injury.

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.

Visual mismatch negativity to masked stimuli presented at very brief presentation rates.

Mismatch negativity (MMN) has been characterised as a 'pre-attentive' component of an event-related potential (ERP) that is related to discrimination and error prediction processes. The aim of the current experiment was to establish whether visual MMN could be recorded to briefly presented, backward and forward masked visual stimuli, given both below and above levels of subjective experience. Evidence of visual MMN elicitation in the absence of the ability to consciously report stimuli would provide strong evidence for the automaticity of the visual MMN mechanism. Using an oddball paradigm, two stimuli that differed in orientation from each other, a + and an ×, were presented on a computer screen. Electroencephalogram (EEG) was recorded from nine participants (six females), mean age 21.4 years. Results showed that for stimuli that were effectively masked at 7 ms presentation, there was little variation in the ERPs evoked to standard and deviant stimuli or in the subtraction waveform employed to delineate the visual MMN. At 14 ms stimulus presentation, when participants were able to report stimulus presence, an enhanced negativity at around 175 and 305 ms was observed to the deviant and was evident in the subtraction waveform. However, some of the difference observed in the ERPs can be attributed to stimulus characteristics, as the use of a 'lonely' deviant protocol revealed attenuated visual MMN components at 14 ms stimulus presentation. Overall, results suggest that some degree of conscious attention is required before visual MMN components emerge, suggesting visual MMN is not an entirely pre-attentive process.

THE PHYSIOLOGY OF THE RETINAL PIGMENT EPITHELIUM IN DANON DISEASE.

PURPOSE: Danon disease is caused by mutations in the lysosome-associated membrane protein-2 gene (LAMP2). In the eye, LAMP2 is expressed only in the retinal pigment epithelium. This study aimed to investigate the previously unreported impact of LAMP2 mutations on the electrooculogram generated by the retinal pigment epithelium. METHODS: Four members of a family with Danon disease were examined. All have mutations in c294G > A, of the LAMP2 gene on Xq24, by which no, or aberrant, protein will be formed. Electrooculograms to International Society for the Clinical Electrophysiology of Vision (ISCEV) standards were recorded with full-field electroretinography, Goldmann kinetic visual fields, and spectral optical coherence tomography with fundus autofluorescence imaging. RESULTS: Electrooculogram amplitude ratios of light rise:dark trough, the Arden index, fell at low-normal limits (range: 1.68-3.94) but misrepresent retinal pigment epithelium health, because the absolute dark trough voltages were abnormally low (median: 140 µV, range: 72-192 µV) as were the light rise amplitudes (median: 297 µV, range: 198-366 µV), and full-field electroretinograms were normal. Hyperfundus autofluorescence and hypofundus autofluorescence changes became more confluent and florid with increasing age of female patients. Goldmann visual field testing showed constriction of the central field. CONCLUSION: Low electrooculogram voltages indicate that the retinal pigment epithelium is unable to maintain its tight junctions in Danon disease.