Retinal defect in children with infantile spasms of varying etiologies: An observational study.

OBJECTIVE: To determine the prevalence of retinal defect in children with infantile spasms (IS) unrelated to treatment with vigabatrin and clarify if specific primary etiologies for IS are associated with retinal defect more than others. METHODS: This was an observational cohort study including 312 patients (176 male, 136 female) with IS who were vigabatrin-naive. Participants ranged from 1.7 to 34.7 months of age (mean 8.8 months). Electroretinograms (ERGs) were performed according to the International Society for Clinical Electrophysiology of Vision. Retinal defect was identified as abnormal if the 30-Hz flicker ERG amplitude was lower than the age-corrected normal 95% prediction interval. The primary etiology for IS, as determined by the treating pediatric neurologist(s), was obtained from patient health records and classified into 1 of 9 etiologic subgroups: (1) genetic disorders alone, (2) genetic-structural disorders, (3) structural-congenital, (4) structural-acquired (perinatal), (5) structural-acquired (postnatal), (6) metabolic disorders, (7) immunologic disorders, (8) infectious, and (9) unknown causes. RESULTS: Fifty-nine of the 312 vigabatrin-naive children (18.9%) showed retinal defect and the prevalence of retinal defect was highest (24.4%) in the structural-acquired (perinatal) subgroup, which included hypoxic-ischemic defect. Retinal function compared across subgroups showed no significant difference. CONCLUSIONS: Care is required in diagnosing retinal toxicity, which would be enhanced by baseline flicker ERG in children with IS prior to starting vigabatrin.

Hand-held, dilation-free, electroretinography in children under 3 years of age treated with vigabatrin.

PURPOSE: The anti-epileptic drug vigabatrin is associated with reduction in light-adapted 30-Hz flicker electroretinogram (ERG) amplitude. Ophthalmological assessments, including ERGs, monitor retinal health during vigabatrin treatment. RETeval™ is a hand-held ERG device adapted for dilation-free ERG assessment. To evaluate the usefulness of RETeval™ for vigabatrin ERG assessment, we evaluated intra-visit reliability and clinical feasibility of RETeval™ ERG assessment in children under 3 years of age undergoing vigabatrin treatment. METHODS: In this prospective study, children underwent 30-Hz flicker ERG assessment with RETeval™ before routine vigabatrin monitoring including sedated-ERG using the Espion E2 Colour Dome. Intraclass correlation coefficient (ICC) statistics identified the degree of intra-visit reliability from two repeated measurements of the same participant within one testing session. The omega squared (ω2) statistic identified the level of association between RETeval™ and Espion light-adapted 30-Hz flicker responses. RESULTS: Nine children completed RETeval™ ERG testing. The intra-visit ICCs for the RETeval™ 30-Hz flicker amplitude (µV) were high: 0.81 (right eye) and 0.86 (left eye), while the implicit times (ms) were 0.79 (right eye) and 0.42 (left eye). The RETeval™ 30-Hz flicker amplitude was positively associated with the Espion 30-Hz flicker response (ω2 = 0.71). The Bland-Altman plot showed no bias in the mean difference of amplitudes between the two systems. CONCLUSION: This is the first study to assess the utility of RETeval™ device in children under 3 years of age undergoing vigabatrin treatment. RETeval™ demonstrated high intra-visit reliability with responses consistent with the standard Espion ERG. RETeval™ may be beneficial for assessment of retinal toxicity in young children treated with vigabatrin.

Demonstration of anatomical development of the human macula within the first 5 years of life using handheld OCT.

PURPOSE: To demonstrate the anatomical development of the human macula using handheld spectral domain optical coherence tomography (SD-OCT) during the first 5 years of life. METHODS: This study is a cross-sectional, observational case series. Thirty-five normal eyes of 35 full-term/late preterm infants and children under 5 years of age were included. Handheld SD-OCT was used to image the macula of each eye. The data were analyzed using the Duke OCT Retinal Analysis Program v17 software. Retinal thickness maps were generated for the total retinal thickness (TRT), the inner retinal layers thickness (IRL), and the photoreceptor layer thickness (PRL). Based on the early treatment diabetic retinopathy study macular map, average thickness measurements were taken at 4 circles centered on the fovea (diameter): the foveal center (0.5 mm), sector 1 (S1) (1 mm), sector 2 (S2) (3 mm), sector 3 (S3) (6 mm). RESULTS: The median age at participation was 24 months (range 5-52 months). The TRT increased throughout the first 5 years of life, and this increase was statistically significant at the foveal center and S1 (p = 0.01, p = 0.016, respectively). The IRL did not show any significant change in thickness from birth and throughout the first 5 years of life. The PRL thickness showed thickening in the first 24 months of age at the foveal center and S1 which was statistically significant at S1 (p = 0.066, p = 0.016, respectively). Interestingly, this PRL thickness increase plateaus beyond 24 months of age. The photoreceptors inner segment/outer segment (IS/OS) band was identified as a distinct layer in all our subjects. CONCLUSION: Our findings conform with the literature that the anatomical development of the macular IRL completes before 5 months of age and hence before the PRL. We also identify 24 months of age as an important developmental milestone for photoreceptors development in the human macula.

VIGABATRIN TOXICITY IN INFANCY IS ASSOCIATED WITH RETINAL DEFECT IN ADOLESCENCE: A Prospective Observational Study.

PURPOSE: The purpose was to determine whether vigabatrin (VGB) (Sabril)-attributed retinal toxicity defined by electroretinogram in early childhood is associated with visual system defect in adolescents after discontinuation of VGB. METHODS: This prospective cross-sectional study included 24 children previously treated with VGB and monitored in early childhood by electroretinogram for VGB-attributed retinal defects. Ten had been diagnosed with VGB-attributed retinal defect (Group I) and 14 had no VGB-attributed retinal defect (Group II). Outcome measures were extent of monocular visual fields using Goldmann kinetic perimetry and RNFL thickness at the optic nerve head, using optical coherence tomography. RESULTS: Of those able to complete testing (6 eyes Group I and 16 eyes Group II), Goldmann results revealed results of visual field loss in Group I and not in Group II. The optical coherence tomography results demonstrated attenuation of the RNFL in all 6 eyes of Group I participants and in only 1 eye of 10 Group II participants. Optical coherence tomography data were nonoverlapping between Group 1 and Group II eyes. CONCLUSION: The VGB-attributed retinal toxicity identified by means of electroretinogram in infancy was associated with visual field loss and RNFL attenuation of the retinal nerve when tested in adolescence.

Measuring recovery of visual function in children with papilledema using sweep visual evoked potentials.

PURPOSE: To assess visual function in children with papilledema using sweep visual evoked potentials (VEP) to determine whether vision function improved following treatment. METHODS: Contrast sensitivity and grating acuity were prospectively measured by using sweep visual evoked potential testing in children with mild or moderate acute papilledema. A subset of children were tested longitudinally before and after treatment. Subject data was compared with that of age-matched controls using the Wilcoxon-Mann-Whitney test. RESULTS: A total of 9 subjects (age range, 9-16 years) and 11 controls were included; 5 subjects were studied longitudinally. The control group's logMAR grating acuity (mean, 0.09; range, -0.13 to 0.36) was better than that of the papilledema group (mean, 0.36; range 0.15-0.59). Four patients showed recovery of contrast sensitivity following treatment of their raised intracranial pressure between first and last visit. CONCLUSIONS: In our study cohort, sweep VEP was able to detect early improvement in contrast sensitivity despite absence of apparent clinical change in disk edema in children undergoing treatment for raised intracranial pressure.

Cone-Photoreceptor Density in Adolescents With Type 1 Diabetes.

PURPOSE: Changes to retinal structure and function occur in individuals with diabetes before the onset of diabetic retinopathy. It is still unclear if these changes initially affect vascular or neural retina, or if particular retinal areas are more susceptible than others. This paper examines the distribution of cone photoreceptor density in the retina of adolescents with type 1 diabetes. METHODS: This cross-sectional prospective study includes 29 adolescents and young adults with type 1 diabetes and no diabetic retinopathy and 44 control participants recruited at the Hospital for Sick Children. Adaptive-optics enhanced retinal imaging of the cone photoreceptor mosaic was performed in four quadrants at an eccentricity of ∼7° from the fovea. After image registration and averaging, cone photoreceptors were counted and photoreceptor density was calculated. Analysis of variance with repeated measures was used to assess the differences in photoreceptor density between groups. RESULTS: Cone density was similar in both control participants and participants with diabetes. There was a small effect of retinal hemisphere; participants with diabetes did not show the expected radial asymmetry observed in control participants. CONCLUSIONS: Cone density in the parafoveal retina is not reduced in adolescents with type 1 diabetes.

Vigabatrin retinal toxicity in children with infantile spasms: An observational cohort study.

OBJECTIVES: To determine time to vigabatrin (VGB, Sabril; Lundbeck, Deerfield, IL) induced retinal damage in children with infantile spasms (IS) and to identify risk factors for VGB-induced retinal damage (VGB-RD). METHODS: Observational cohort study including 146 participants (68 female, 81 male) with IS, an age-specific epilepsy syndrome of early infancy, treated with VGB. Participants ranged from 3 to 34.9 months of age (median 7.6 months). The median duration of VGB treatment was 16 months (range 4.6-78.5 months). Electroretinograms (ERGs) were performed according to the Standards of the International Society for Clinical Electrophysiology of Vision. Inclusion required baseline (pre-VGB or within 4 weeks of starting VGB treatment) and at least 2 follow-up ERGs. Significant reduction from baseline of the 30-Hz ERG flicker amplitude on 2 consecutive visits identified VGB-RD. Kaplan-Meier survival analyses depicted the effect of duration of VGB on VGB-RD. RESULTS: These data represent the largest survival analysis of children treated with VGB who did not succumb to retinal toxicity during the study. Thirty of the 146 participants (21%) showed VGB-RD. The ERG amplitude reduced with duration of VGB treatment (p = 0.0004) with no recovery after VGB cessation. With 6 and 12 months of VGB treatment, 5.3% and 13.3%, respectively, developed VGB-RD. There was neither effect of age of initiation of VGB treatment nor sex of the child on survival statistics and no significant effect of cumulative dosage on the occurrence of VGB-RD. CONCLUSIONS: Minimizing VGB treatment to 6 months will reduce the prevalence of VGB-RD in patients with IS.

OTX2 mutations cause autosomal dominant pattern dystrophy of the retinal pigment epithelium.

PURPOSE: To identify the genetic cause of autosomal-dominant pattern dystrophy (PD) of the retinal pigment epithelium (RPE) in two families. METHODS AND RESULTS: Two families with autosomal-dominant PD were identified. Eight members of family 1 (five affected) were subjected to whole-genome SNP genotyping; multipoint genome-wide linkage analysis identified 7 regions of potential linkage, and genotyping four additional individuals from family 1 resulted in a maximum logarithm of odds score of 2.09 observed across four chromosomal regions. Exome sequencing of two affected family 1 members identified 15 shared non-synonymous rare coding sequence variants within the linked regions; candidate genes were prioritised and further analysed. Sanger sequencing confirmed a novel heterozygous missense variant (E79K) in orthodenticle homeobox 2 (OTX2) that segregated with the disease phenotype. Family 2 with PD (two affected) harboured the same missense variant in OTX2. A shared haplotype of 19.68 cM encompassing OTX2 was identified between affected individuals in the two families. Within the two families, all except one affected demonstrated distinct 'patterns' at the macula. In vivo structural retinal imaging showed discrete areas of RPE-photoreceptor separation at the macula in all cases. Electroretinogram testing showed generalised photoreceptor degeneration in three cases. Mild developmental anomalies were observed, including optic nerve head dysplasia (four cases), microcornea (one case) and Rathke's cleft cyst (one case); pituitary hormone levels were normal. CONCLUSIONS: This is the first report implicating OTX2 to underlie PD. The retinal disease resembles conditional mice models that show slow photoreceptor degeneration secondary to loss of Otx2 function in the adult RPE.

The characterization of retinal phenotype in a family with C1QTNF5-related late-onset retinal degeneration.

PURPOSE: To describe the clinical, spectral-domain optical coherence tomography and electrophysiological features of C1QTNF5-associated late-onset retinal degeneration in a molecularly confirmed pedigree. METHODS: Five members of a family participated, and affected individuals (n = 4) underwent detailed ophthalmologic evaluation including fundus autofluorescence and spectral-domain optical coherence tomography imaging and electroretinography. Electrooculography was performed in three individuals. RESULTS: The visual acuity was initially normal and worsened with time. Anterior segment abnormalities included peripupillary iris atrophy and long anterior insertion of zonules. Peripapillary atrophy, drusenoid deposition, and scalloped sectorial chorioretinal atrophy were observed in all older individuals (n = 3). Fundus autofluorescence demonstrated hypofluorescent areas corresponding to regions of chorioretinal atrophy. The spectral-domain optical coherence tomography demonstrated multiple areas of retinal pigment epithelium-Bruch membrane separation with intervening homogeneous deposition that corresponded to the drusenoid lesions and areas of chorioretinal atrophy. Electrooculography was normal in one individual and showed abnormally low dark trough measures in older individuals (n = 2). Electroretinography was normal in early stages (n = 1), but showed marked abnormalities in the rod system (n = 3), which was predominantly inner retinal (n = 2) in late stages. CONCLUSION: Late-onset retinal degeneration is a progressive degeneration, and anterior segment abnormalities present early. The widespread sub-retinal pigment epithelium deposition seen on spectral-domain optical coherence tomography in older individuals appears to be a characteristic in late stages. Electrooculography demonstrates abnormalities only in late stages of the disease.

Blue flash ERG PhNR changes associated with poor long-term glycemic control in adolescents with type 1 diabetes.

PURPOSE: To investigate the relationship between long-term glycemic control and photopic negative response (PhNR) changes in the blue flash ERG in adolescents with type 1 diabetes (T1D) without diabetic retinopathy (DR). METHODS: After light adaptation, ERG responses to 1.60 cd·s/m(2) blue (420 nm) flashes (blue flash ERG) and 3.0 cd·s/m(2) white flashes (LA 3.0 ERG) were recorded in 22 patients (age range, 12 to 19 years) and 28 age-similar control subjects. The primary outcome measure was the amplitude of the PhNR. Secondary outcome measures were the amplitude and implicit time of the a-wave and b-wave. Multiple regression analyses were conducted with glycated hemoglobin (HbA(1c)) values and the time since diagnosis of T1D as covariates. RESULTS: Blue flash ERG PhNR amplitudes were reduced (P = 0.005) in patients compared with control subjects. Multiple regression analysis demonstrated that a 1-unit increase in HbA(1c) was associated with a 15% decrease in the blue flash ERG PhNR amplitude (r = 0.61, P = 0.003). Compared with controls blue flash ERG a-waves (P = 0.03) and b-waves (P = 0.02) were delayed in patients but were not significantly associated with HbA(1c) or time since diagnosis of T1D. None of the ERG measures in the LA 3.0 ERG were significantly different in patients compared with controls. CONCLUSIONS: Poorer long-term glycemic control is associated with worsening inner retinal dysfunction involving short-wavelength cone pathways of adolescents with T1D and no clinically visible DR. Future studies are warranted to determine whether changes in the blue flash ERG PhNR are a predictive marker of subclinical DR.

A novel p.Gly603Arg mutation in CACNA1F causes Åland island eye disease and incomplete congenital stationary night blindness phenotypes in a family.

PURPOSE: To report, for the first time, that X-linked incomplete congenital stationary night blindness (CSNB2A) and Åland island eye disease (AIED) phenotypes coexist in a molecularly confirmed pedigree and to present novel phenotypic characteristics of calcium channel alpha-1F subunit gene (CACNA1F)-related disease. METHODS: Two affected subjects (the proband and his maternal grandfather) and an unaffected obligate carrier (the proband's mother) underwent detailed ophthalmological evaluation, fundus autofluorescence imaging, and spectral-domain optical coherence tomography. Goldmann visual field assessment and full-field electroretinogram (ERG) were performed in the two affected subjects, and multichannel flash visual evoked potential was performed on the proband. Scotopic 15 Hz flicker ERG series were performed in both affected subjects to evaluate the function of the slow and fast rod pathways. Haplotype analysis using polymorphic microsatellite markers flanking CACNA1F was performed in all three family members. The proband's DNA was sequenced for mutations in the coding sequence of CACNA1F and nyctalopin (NYX) genes. Segregation analysis was performed in the family. RESULTS: Both affected subjects had symptoms of nonprogressive nyctalopia since childhood, while the proband also had photophobia. Both cases had a distance visual acuity of 20/50 or better in each eye, normal contrast sensitivity, and an incomplete type of Schubert-Bornschein ERGs. The proband also had high myopia, a mild red-green color deficit, hypopigmented fundus, and foveal hypoplasia with no evidence of chiasmal misrouting. Spectral-domain optical coherence tomography confirmed the presence of foveal hypoplasia in the proband. The clinical phenotype of the proband and his maternal grandfather fit the clinical description of AIED and CSNB2A, respectively. The fundus autofluorescence and the visual fields were normal in both cases; the scotopic 15 Hz flicker ERG demonstrated only fast rod pathway activity in both. Both affected cases shared the same haplotype across CACNA1F. The proband carried a novel hemizygous c.1807G>C mutation (p.G603R) in the CACNA1F gene. The change segregated with the disease phenotypes and was not identified in 360 control chromosomes. No mutations were identified in NYX. CONCLUSIONS: This report of a missense mutation in CACNA1F causing AIED and CSNB2A phenotypes in a family confirms that both diseases are allelic and that other genetic or environmental modifiers influence the expression of CACNA1F. This is the first report to suggest that in CACNA1F-related disease, the rod system activity is predominantly from the fast rod pathways.

ISCEV standard for clinical electro-oculography (2010 update).

The clinical electro-oculogram (EOG) is an electrophysiological test of function of the outer retina and retinal pigment epithelium (RPE) in which changes in electrical potential across the RPE are recorded during successive periods of dark and light adaptation. This document presents the 2010 EOG Standard from the International Society for Clinical Electrophysiology of Vision (ISCEV: www.iscev.org ). This revision has been reorganized and updated, but without changes to the testing protocol from the previous version published in 2006. It describes methods for recording the EOG in clinical applications and gives detailed guidance on technical requirements, practical issues, and reporting of results. It is intended to promote consistent quality of testing and reporting within and between clinical centers.

Electroretinogram changes in a pediatric population with epilepsy: is vigabatrin acting alone?

Vigabatrin, a structural analogue of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA), is widely used as initial monotherapy in infantile spasms and add on therapy in partial onset seizures. Vigabatrin is associated with retinal toxicity causing constriction of the visual field. Our aim was to assess what effect add-on antiepileptic drug therapy has on the incidence of retinal toxicity in patients being treated with vigabatrin. Medication dosages, duration of treatment, and electroretinogram results were examined in a single center retrospective study. Retinal toxicity was detected in 18 of 160 patients (11.25%) over a 10-year period. A total of 14 (77%) were in the group treated with additional antiepileptic drugs, the other 4 received vigabatrin as monotherapy. We detected a significantly higher percentage of toxicity in the group of patients treated with vigabatrin and additional antiepileptic drugs. Our numbers were not sufficient to detect which drug or combination of drugs might be associated with higher risk.

Vigabatrin-associated reversible MRI signal changes in patients with infantile spasms.

PURPOSE: To evaluate the magnetic resonance imaging (MRI) of pediatric patients with infantile spasms (IS) treated with vigabatrin (VGB) in order to investigate whether VGB affects the brain. METHODS: One hundred seven pediatric patients diagnosed with IS and treated with (n = 95) >or=120 mg/kg/day VGB or without (n = 12) VGB were included. MRI and diffusion-weighted imaging (DWI) were retrospectively analyzed. RESULTS: Of the patients who had MRI scans during, but not before, VGB treatment (n = 81), 25 (30.9%) exhibited abnormal MRI signal intensity and/or restricted DWI in the deep gray nuclei and brainstem. Follow-up scans (performed in 15 of the 25 patients) revealed that these changes were reversible upon withdrawal of the medication. Analysis of patients undergoing scans before, during, and after VGB treatment (n = 14) revealed that four patients had abnormal MRI signal during treatment with VBG, two of whom reversed with cessation of VGB, one reversed without cessation of VGB, and another had persistent abnormal signal while being weaned from the VGB. Patients who had not received VGB treatment (n = 12) displayed normal imaging. Younger infants (

Paradoxical robust visual evoked potentials in young patients with cortical blindness.

The objective of this study was to review retrospectively cases of clinically blind children in whom robust pattern visual evoked potentials (VEPs) were recorded. VEP records from a 10-year period (1990-2000) were reviewed. We searched for charts of children who were clinically cortically blind, but in whom assessment of visual acuity, using visual evoked potentials (VEPs), was normal or close to normal. The majority (77.5%) of VEP and behavioral acuity measures were concordant (subset analysis). Of the 1,113 VEP records, 9 cases (<1% of records reviewed) had clinically compromised vision with fair to good levels of visual function using VEPs. The commonality among the cases was the presence of suspected cortical visual impairment with seizures and developmental delay. VEP acuity cannot be correlated unequivocally with visually guided behaviour. In specific cases, particularly cases with developmental delay and neuroradiographic abnormalities, a child who is behaviorally blind with no clinical evidence of vision may show robust VEPs even to small patterns. This finding might be consistent with a defect of the visual association cortex.

Reduced grating acuity associated with retinal toxicity in children with infantile spasms on vigabatrin therapy.

PURPOSE: To determine whether visual functions are decreased in children with infantile spasms and vigabatrin-attributed retinal toxicity. METHODS: Contrast sensitivity and grating acuity were measured by using sweep visual evoked potential (VEP) testing in 42 children with infantile spasms (mean age, 29.23 +/- 18.31 months). All children had been exposed to vigabatrin (VGB) for a minimum of 1 month. These children were divided into retinal toxicity and no toxicity groupings based on 30-Hz flicker amplitude reductions on the full-field electroretinogram. A multivariate analysis of variance (MANOVA) compared visual functions between children with and without retinal toxicity. RESULTS: The MANOVA showed that visual function was significantly affected by VGB retinal toxicity. Further univariate analysis revealed that grating acuity was significantly reduced in children with toxicity. No differences in contrast sensitivity were found between children with toxicity and those without. CONCLUSIONS: Reduced visual functions from VGB-attributed retinal toxicity can be detected in children with infantile spasms with the sweep VEP.

Rod a-wave analysis using high intensity flashes adds information on rod system function in 25% of clinical ERG recordings.

PURPOSE: To investigate whether rod a-wave analysis using high intensity flashes adds information above that obtained with standard ERG. METHODS: A total of 2,396 eyes were recorded. Patient age was 2.4 months-84.6 years. RESULTS: A-wave analysis of high intensity flashes provided additional information on rod system function in 25% of eyes recorded, most importantly in subjects with midretinal disease and artificially reduced rod responses. High intensity flashes also provided measurable responses for longitudinal monitoring in rod dystrophies with non-recordable rod ERGs. CONCLUSIONS: Clinical ERG testing would benefit greatly from adding high intensity flashes to its standard testing conditions.

Contrast sensitivity is reduced in children with infantile spasms.

PURPOSE: To investigate whether visual deficits in children with infantile spasm (IS) are the result of seizure activity or of treatment with the anticonvulsant drug vigabatrin (VGB). METHODS: Vision function was determined in three experiments by determining peak contrast sensitivity (CS) and grating acuity (GA) with the sweep visual evoked potential. Cross-sectional study A: 34 children, including 11 patients with childhood epilepsy with exposure to VGB for at least 6 months, 10 with childhood epilepsy exposed to antiepileptic drugs other than VGB, and 13 normally developing children. Cross-sectional study B: 32 children, including 16 with IS naïve to VGB and 16 normally developing children. Longitudinal study: seven children with IS naïve to VGB, with subsequent follow-up 5 to 10 months after starting VGB. RESULTS: In cross-sectional study A, the median CS was reduced by 0.5 log units (P = 0.025) in children with epilepsy exposed to VGB compared with those exposed to other antiepileptic drugs and normally developing children. In cross-sectional study B, the median CS was reduced by 0.25 log units (P = 0.0015) in children with IS (VGB naïve) compared with normally developing children. Longitudinal assessment showed no decrease in CS in children with IS who were followed up 5 to 10 months after starting VGB. There was no difference in GA among groups in any of the experiments. CONCLUSIONS: Patients with IS have CS deficits, but a sparing of GA. This deficit is present before VGB treatment and does not worsen with treatment onset. Results suggest that visual dysfunction is largely the result of the seizures themselves.

Screening and diagnosis of optic pathway gliomas in children with neurofibromatosis type 1 by using sweep visual evoked potentials.

PURPOSE: Neurofibromatosis type 1 (NF-1) is an autosomal dominant phakomatosis with a prevalence of 1 in 2000 to 1 in 5000. Up to 24% of these patients have optic pathway gliomas (OPGs). In the present study, the use of sweep visual evoked potentials (SVEPs) was investigated as a screening tool for identifying patients with NF-1 who had OPGs by comparing them to those patients with no OPGs and to normally developing children. METHODS: Contrast sensitivity and grating acuity were measured with the SVEP. Sixteen children with OPGs (OPG group), 14 children with NF-1 without OPGs (nOPG), and 16 aged-matched control subjects were recruited. All participants had best-corrected visual acuity of 6/9 or better. All were tested monocularly. RESULTS: Comparisons between groups by using the Tukey B test showed a significant reduction of mean log contrast sensitivity in the OPG group (1.55) compared with the nOPG (1.9, P = 0.006) and control (2.10, P < 0.001) group. There was no significant difference between the nOPG and control groups (P = 0.195). Grating acuity was comparable between groups, and no statistically significant differences were found. Log contrast sensitivity was moderately sensitive in identifying patients with OPG and was highly specific in screening out patients with no OPG. CONCLUSIONS: Children with OPGs have reduced contrast sensitivity when assessed using the SVEP. Children with no OPGs display no differences in visual functioning compared with control subjects. The findings suggest that the SVEP can be a useful and noninvasive screening tool for early detection of visual pathway gliomas in children with NF-1 and normal visual acuity.