Carole M. Panton

Values of electroretinogram responses according to axial length

Accurate interpretation of electroretinograms (ERGs) requires knowledge of effects of axial myopia on ERG responses. Our purpose was to derive expected changes of ERG responses according to axial length, to stimulus conditions that conform to the International Society for Clinical Electrophysiology of Vision (ISCEV) Standard for Electroretinography. ERGs from 60 subjects were recorded. The subjects were assigned to one of three groups according to the level of myopia. Thirty-three subjects had high myopia (−6.00 D to −14.50 D; mean age, 31 years), eight had mild myopia (−3.00 D to −5.00; mean age, 28 years), and 19 had a small refractive error (+0.75 D to −2.75 D; mean age, 27 years). No subjects had myopic retinopathy. Stimulus-response curves were fitted to dark-adapted b-wave amplitudes and maximum amplitude and semi-saturation constants derived. Axial lengths, measured with A scan ultrasound, ranged from 22.2 mm to 30.0 mm. Analysis of variance and post hoc t-tests revealed significant difference between subjects with high myopia and subjects with small refractive error for ERG amplitude data. There were no significant differences between the three groups for implicit times, the ratio of b- to a-wave and semi-saturation constant. There is linear reduction in the logarithmic transform of ERG amplitude with increasing axial length, related more to axial length than refractive error. We provide relative slope and intercept values, allowing labs to derive expected ERG amplitudes according to axial length. These derivations are valid for persons with no retinopathy.

Time courses for maturation of electroretinogram responses from infancy to adulthood.

The purpose of this study was to determine how responses in the normal human electroretinogram (ERG) change with subject age. We studied 62 children, 10 days to 15 years old, and 30 subjects 15–37 years old, using the standard protocol established by the International Society for Clinical Electrophysiology of Vision, with Burian-Allen bipolar contact-lens electrodes. We measured rod response, maximal response, oscillatory potentials (OPs), cone response, flicker response, and b-wave amplitude/log intensity (V/log I) curve. A logistic growth curve was used to describe the developmental changes. Dark- and light-adapted ERG a- and b-wave amplitudes reached adult levels by three to five years of age, although b-wave amplitudes of scotopic rod-mediated responses were slower to reach maturity than mixed rod-cone mediated responses. In early infancy OPs were the most immature of the ERG responses, although the rate of development thereafter exceeded that of the other responses such that OP amplitudes were within adult levels by two years of age. Amplitudes of the ERG responses in 21 children sedated with chloral hydrate did not differ significantly from 21 who had not been sedated. ERG responses developed at varying rates, reflecting different developmental stages in photoreceptors, middle retinal layers and more proximal retina.

Ocular phenotypes of three genetic variants of Bardet-Biedl syndrome

Bardet–Biedl syndrome is a genetically heterogeneous multisystem disorder that causes severe visual impairment. Retinitis pigmentosa (RP), hypogonadism, digit and renal anomalies, obesity, and a variable degree of mental retardation characterize the disorder. Eight different loci have been identified on 2q31(BBS5), 3p13 (BBS3), 4q27 (BBS7), 11q13 (BBS1), 14q32 (BBS8), 15q22.3 (BBS4), 16q21 (BBS2), and 20p12 (BBS6). The ocular manifestations of Bardet–Biedl syndrome include an early and severe rod‐cone dystrophy causing legal blindness in the second decade. Features of systemic phenotypic variability were proposed to distinguish patients mapped to either the BBS2, BBS3, or BBS4 loci but no phenotype–genotype correlation has been established for the ocular phenotype. We studied the three original families used for the identification of BBS2, BBS3, and BBS4 loci to define the ocular phenotypes of patients (n = 34) and obligate carriers (n = 32) using clinical examination and electroretinography (ERG). RP was severe and early in all cases. Myopia was associated with BBS3 and BBS4, but not BBS2. One patient with Bardet–Biedl syndrome also had iris and chorioretinal colobomata, features suggestive of Biemond syndrome.

The Hospital for Sick Children, Toronto, Longitudinal ERG study of children on vigabatrin.

The purpose of this longitudinal study was to identify changes in ERG responses associated with vigabatrin treatment. We accomplished this by recording longitudinally ERGs in children before and during vigabatrin treatment and comparing results between children on vigabatrin monotherapy and those taking additional anticonvulsive medications. Thirty-three children on vigabatrin therapy were tested; the duration between visits was approximately 6 months. Thirteen children were assessed initially before starting vigabatrin therapy and seven were assessed soon after (age range 1.5–126 months, median 6 months). The remaining 13 patients were already on vigabatrin at the time of initial visit (age range 6.5–180 months, median 16 months). ERGs were tested using the standard protocol established by the International Society for Clinical Electrophysiology of Vision, with Burian-Allen bipolar contact-lens electrodes. In addition to standard responses we recorded photopic oscillatory potentials (OPs). All 33 patients were tested longitudinally on at least two occasions and 11 were tested on three occasions. For children whose only anticonvulsive drug was vigabatrin there was a significant curvature (quadratic function, p<0.05) of the predicted cone b-wave amplitude with time; exhibited as increase in b-wave amplitude followed by subsequent decrease. Descriptive data demonstrated the same pattern in the group taking anticonvulsive medications in addition to vigabatrin. In most children the flicker amplitude declined between 6 months and 1 year of vigabatrin treatment. Our data demonstrated that rod responses, which may be abnormal before initiation of vigabatrin, did not change substantially with vigabatrin treatment.

Changes in the electroretinogram resulting from discontinuation of vigabatrin in children

Electroretinograms (ERGs) have been recorded longitudinally in children before and during treatment with the antiepileptic drug vigabatrin for the past 3.5 years. Vigabatrin induced changes in ERG responses occur in children; the most dramatic changes occur in the oscillatory potentials. The purpose of this study was to identify changes in ERG responses associated with discontinuation of vigabatrin treatment. If vigabatrin-induced changes reverse after discontinuation of the drug we infer that the original change is not an indicator of toxicity. ERG data were analyzed from 17 children who discontinued vigabatrin therapy. The duration of treatment ranged from 5 to 52 months, the age for the first ERG ranged from 6 to 38 months (median 10 months). ERGs were tested using the standard protocol established by the International Society for Clinical Electrophysiology of Vision, with Burian-Allen bipolar contact-lens electrodes. In addition to standard responses we recorded photopic oscillatory potentials (OPs). During vigabatrin treatment OPs show a greater change than other ERG responses, with the early occurring wavelets from the photopic OPs showing the greatest change. With discontinuation of vigabatrin the amplitude of the early wavelets of the photopic OPs increased dramatically compared with amplitudes while taking the drug (paired t-test, p=0.000075). The scotopic oscillatory potentials also show some recovery. Although changes in oscillatory potentials may occur with vigabatrin toxicity, a large change likely occurs with a non-toxic pharmacological effect of vigabatrin on GABAergic amacrine cells in the inner plexiform layer. Reduction of OPs in children on vigabatrin may not be related to toxicity.

Longitudinal changes in photopic OPs occurring with vigabatrin treatment

Purpose: Vigabatrin (γ-vinyl-GABA) is an antiepileptic drug successful in the management of infantile spasms. Photopic ERGs were tested in children followed longitudinally before and during vigabatrin treatment. Methods: Subjects were 26 infants (age range 1.5–24 months, median 7.6 months) on vigabatrin treatment who had been tested on multiple visits (two to four visits; mean, three visits). Eighteen of these were assessed initially before starting vigabatrin therapy and eight were assessed within 1 week of initiation of the drug. ERGs were recorded at 6-month intervals. Standard ISCEV protocol with Burian-Allen bipolar contact-lens electrodes (standard flash 2.0 cd.s/m2) was used. Although ISCEV standards were followed, a higher flash intensity (set at 3.6 cd.s/m2) was chosen for single-flash cone assessment to provide a better definition of OPs. Photopic OPs were divided into categories of early OPs and late OP (OP4). Responses were compared with age corrected limits extrapolated from our lab control database. Results: Results showed differential effects of vigabatrin on the summed early OP amplitudes versus the late OP (OP4) and cone b-wave amplitude. The early OPs showed significant decrease (p=0.0005, repeated measures analysis of variance) after 6 months and remained decreased for the duration of treatment. There was no significant change seen in the late OP. The cone b-wave amplitude showed initial increase (p=0.04) after 6 months, followed by a decrease after 18 months; a trend similar to that of the late OP. Conclusion: Early photopic OPs were disrupted more than the late OP, suggesting relative deficit in the ON (depolarizing) retinal pathways.

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.

Dynamic Fusional Vergence Eye Movements in Congenital Esotropia

Purpose: To evaluate whether a selected group of 9 children with history of congenital esotropia is capable of producing vergence eye responses to fusional disparity stimuli. Methods: Nine children with history of congenital esotropia and 5 age-matched children with normal binocular vision were examined. Using a full-field target, vergence responses to base out 3 prism diopters placed in front of both eyes were recorded. Results: In five patients, the initial response was a saccade generated by the dominant eye, followed by a disconjugate movement of one or both eyes. In two patients with long standing uncorrected strabismus, the responses were almost purely saccadic, while in two other patients, in whom early surgery resulted in fusional abilities, smooth vergence movements were recorded. Conclusion: This study adds further evidence that patients with history of congenital esotropia patients are capable of producing vergence eye movements in response to fusional disparity. The responses usually start with a saccade followed by a vergence response. The preference for initial saccadic or vergence response is correlated with sensorial tests of stereopsis and motor fusion and may be related to the size of the suppression scotoma in the deviating eye, the duration of misalignment, or both.