Pediatric abusive head trauma: visual outcomes, evoked potentials, diffusion tensor imaging, and relationships to retinal hemorrhages.

PURPOSE: Function and anatomy of the visual system were evaluated in children with abusive head trauma (AHT). The relationships between retinal hemorrhages at presentation were examined with outcome measures. METHODS: Retrospective review of data in children with AHT for 1) visual acuity at last follow-up, 2) visual evoked potentials (VEP) after recovery, 3) diffusion metrics of white matter tracts and grey matter within the occipital lobe on diffusion tensor imaging (DTI), and 4) patterns of retinal hemorrhages at presentation. Visual acuity was converted into logarithm of minimum angle of resolution (logMAR) after correction for age. VEPs were also scored by objective signal-to-noise ratio (SNR). RESULTS: Of 202 AHT victims reviewed, 45 met inclusion criteria. Median logMAR was reduced to 0.8 (approximately 20/125 Snellen equivalent), with 27% having no measurable vision. Thirty-two percent of subjects had no detectable VEP signal. VEPs were significantly reduced in subjects initially presenting with traumatic retinoschisis or hemorrhages involving the macula (p < 0.01). DTI tract volumes were decreased in AHT subjects compared to controls (p < 0.001). DTI metrics were most affected in AHT victims showing macular abnormalities on follow-up ocular examination. However, DTI metrics were not correlated with visual acuity or VEPS. There was large inter-subject variability within each grouping. DISCUSSION: Mechanisms causing traumatic retinoschisis, or traumatic abnormalities of the macula, are associated with significant long-term visual pathway dysfunction. AHT associated abnormalities of the macula, and visual cortical pathways were more fully captured by VEPs than visual acuity or DTI metrics.

Optical Coherence Tomography and Visual Outcomes in Pediatric Abusive Head Trauma.

PURPOSE: Compare follow-up optical coherence tomography (OCT) with visual function in children with abusive head trauma (shaken baby syndrome). METHODS: Retrospective follow-up studies of 3 children who were victims of abusive head trauma (AHT) within the first year of life. RESULTS: OCTs showed disrupted retinal layering, thick detached internal limiting membrane, focal posterior vitreous separation, and multilayered tractional retinoschisis. Significant vision loss occurred in 3 out of 4 eyes with a history of traumatic retinoschisis. Normal visual acuity and low-normal visual evoked potentials were measured in a child with foveal distortion, reduced global nerve fiber layer thickness, detached internal limiting membrane, and history of vitreous hemorrhage. DISCUSSION: Significant abnormalities of retinal anatomy can be detected on OCT years after AHT. OCTs and assessment of visual pathways help to elucidate causes of visual dysfunction in children with AHT.

Cerebral Visual Impairment Characterized by Abnormal Visual Orienting Behavior With Preserved Visual Cortical Activation.

Purpose: Children with cerebral visual impairment (CVI) often have abnormal visual orienting behaviors due to impaired or damaged visual cortex. Alternatively, visual-cortical function is intact but visual information is not transformed downstream into an appropriate oculomotor output (visuomotor dysfunction). We examined visual, anatomic, and oculomotor assessments to distinguish visuomotor dysfunction from CVI associated with severely reduced visual-cortical response. Methods: We reviewed the medical records from children with CVI having abnormal visual orienting behaviors, normal ocular examinations, and born near term. Relevant data were visual evoked potentials (VEPs), Teller card acuity, eye movements recorded by video-oculography (VOG), and neuroimaging (magnetic resonance imaging [MRI]) including diffusion tensor imaging (DTI) tractography. Results: Thirty subjects had visuomotor dysfunction based on a normal VEP; of these 33% had a normal MRI and 67% had white matter abnormalities associated with metabolic disease and/or decreased volume of brain parenchyma. VOG recordings showed smooth pursuit gains were uniformly reduced and saccades were dysmetric but followed the main sequence. Ten subjects had severe CVI based on VEPs at noise levels; visual acuities and MRI findings overlapped those of the visuomotor dysfunction group. Developmental delay, seizures, microcephaly, and hypotonia were common across all groups. All subjects with an abnormal conventional MRI had abnormal metrics on DTI tractography from the occipital lobe. Conclusions: A subset of patients with CVI have abnormal visual orienting behaviors despite a normal VEP (visuomotor dysfunction). A majority have abnormal white matter metrics on tractography suggesting a downstream defect in sensorimotor transformation. Clinically, visuomotor dysfunction is indistinguishable from severe CVI.

A reduced visual pathway response in infantile nystagmus syndrome.

PURPOSE: To investigate visual cortical responses in children with infantile nystagmus syndrome (INS) and the potential contribution of foveation periods. METHODS: The medical records of children with INS who had visual evoked potential (VEP) recordings to reversing checkerboards and onset of horizontal gratings were reviewed retrospectively. VEP recordings underwent objective selective averaging for extraction of brief periods having consistent amplitude and timing with the stimulus presentation. VEP amplitude, latency, and signal-to-noise ratios (SNR) were compared to results from published age-matched controls under the same conditions. Relative foveation in INS subjects was determined from the proportion of time a video-oculography recording met eye position and velocity criteria. RESULTS: A total of 26 children met inclusion criteria. Selective averaging increased VEP amplitude and SNR in INS by 270%-420% compared to standard averaging (P < 0.0001). The INS change in VEP response was greater for reversing checkerboard stimulation than horizontal-grating onset and was significantly greater than that in controls (P < 0.001). Latency was not changed by selective averaging. Relative foveation was correlated with increasing VEP amplitude (P = 0.02) and number of trials chosen for selective averaging (P < 0.01). After selective averaging, relative foveation correlated with VEP amplitude to reversing checkerboards only (P = 0.007). CONCLUSIONS: Nystagmus likely causes a reduced visual cortical response in children with INS. A significantly larger response can be extracted from brief periods during nystagmus eye movements, supporting the hypothesis that the INS visual system generates a larger cortical signal during brief foveation periods.

Two Missense CACNA1A Variants in a Single Family with Variable Neurobehavioral, Cerebellar, Epileptic, and Oculomotor Features.

We describe two novel missense variants in CACNA1A segregating in a family with variable severity of ataxia/oculomotor dysfunction, neurobehavioral impairments, and epilepsy. The most severe outcome occurred in a compound heterozygous proband, which could represent variable expression of the paternal allele or biallelic modulation of calcium channel function. Acetazolamide and lamotrigine were effective for seizure control.

Matching Misaligned Spectralis OCTs to a Reference Scan in Pediatric Glaucoma with Poor Fixation and Nystagmus.

Purpose: Poor fixation or nystagmus in children causes misalignment errors when measuring circumpapillary retinal nerve fiber layer (cpRNFL) thickness by simultaneous scanning laser ophthalmoscope imaging/optical coherence tomography (SLO/OCT). We investigated a method to assess cpRNFL from misaligned SLO/OCT scans. Methods: Heidelberg Spectralis SLO/OCT scans from a single clinical examination were retrospectively analyzed when automated eye tracking was unreliable. Retinal layer thickness was measured at overlapping match locations between a reference and misaligned scans based on the position data from simultaneously acquired SLO images. Three layers were segmented: cpRNFL, internal limiting membrane to outer nuclear layer (ILM-ONL), and total retinal thickness (TR). Accuracy was defined as the difference in thickness between the reference and misaligned scans at their match locations after correction for scan angle. Results: Thirty-five subjects, evaluated for glaucomatous nerve loss, met inclusion criteria. Group-averaged accuracy was -2.7, 1.4, and 0.3 µm for cpRNFL, ILM-ONL, and TR thickness, respectively. Across all layers, interobserver intraclass correlation coefficients ranged from 0.97 to 0.63 and the maximum Bland-Altman 95% limits of agreement were -21.6 to 20.7 µm. Variability was greatest for cpRNFL thickness and least for TR thickness. Increased variability was associated with lower signal-to-noise ratio but not with image-motion indices of shear, rotation, and scale. Conclusions: Retinal layer thickness can be compared to a reference cpRNFL OCT scan when poor fixation and nystagmus causes misalignment errors. The analysis can be performed post hoc using multiple misaligned scans from standard SLO/OCT protocols. Translational Relevance: Our method allows for assessment of cpRNFL in children who fail eye tracking.

Optical coherence tomography findings in Cohen syndrome.

Cohen syndrome is a rare disease that causes myopia and retinal degeneration in the setting of developmental delay and characteristic craniofacial features. We report optical coherence tomography (OCT) abnormalities in 4 patients with Cohen syndrome, 2 of whom have longitudinal follow-up. All subjects had schisis-like changes, with cystoid spaces in the inner retina as well as diffuse outer retinal atrophy sparing the subfoveal region. Ophthalmologic findings in 1 patient led to the work-up that resulted in a diagnosis of Cohen syndrome, suggesting that characteristic retinal abnormalities visualized by fundus examination and OCT may represent distinguishing features of this syndrome.

Retinal and visual function in infants with non-accidental trauma and retinal hemorrhages.

PURPOSE: To investigate retinal function and visual outcomes in infants with retinal hemorrhages due to non-accidental trauma (NAT). METHODS: This is a retrospective review of full-field or multifocal electroretinogram (ERG) recordings, visual acuity in log minimum angle of resolution (logMAR), clinical status, and neuroimaging. Multifocal ERGs from the central 40° were compared to corresponding fundus imaging. Visual acuity was measured by Teller cards at follow-up. ERGs were compared to controls recorded under anesthesia. RESULTS: Sixteen children met inclusion criteria (14 recorded during the acute phase and 2 during long-term follow-up). During the acute phase, ERGs (n = 4 full field; n = 10 multifocal ERG) showed abnormal amplitude, latency, or both in at least one eye. Ten subjects had significantly reduced responses in both eyes, 3 of which had an ERG dominated by a negative waveform (absent b-wave or P1). The remaining six subjects had responses in one eye that were near normal (≥ 50% of controls). ERGs were sometimes abnormal in local areas without hemorrhage. ERGs could be preserved in local areas adjacent to traumatic retinoschisis. Two subjects with reduced visual acuity had belated ERGs: One had an abnormal macular ERG and the other had a normal macular ERG implying cortical visual impairment. At follow-up, 10 of 14 subjects had significant visual acuity loss (≥ 0.7 age-corrected logMAR); four subjects had mild vision loss (≤ 0.5 age-corrected logMAR). Visual acuity outcome was not reliably associated with the fundus appearance in the acute phase. All subjects with a negative ERG waveform had severe vision loss on follow-up. CONCLUSIONS: Retinal dysfunction was common during the acute phase of NAT. A near normal appearing fundus did not imply normal retinal function, and ERG abnormality did not always predict a poor visual acuity outcome. However, a negative ERG waveform was associated severe visual acuity loss. Potential artifacts of retinal hemorrhages and anesthesia could not fully account for multifocal ERG abnormalities. Retinal function can be preserved in areas adjacent to traumatic retinoschisis.

Visual Function, Brain Imaging, and Physiological Factors in Children With Asymmetric Nystagmus due to Chiasmal Gliomas.

PURPOSE: Asymmetric nystagmus can be an important presenting sign of optic pathway gliomas in young children. We investigated the causes of asymmetric nystagmus in children with chiasmal or suprasellar optic pathway gliomas compared with children with similar optic pathway gliomas and stable gaze. METHODS: Longitudinal magnetic resonance imaging before and after treatment, age-corrected visual acuity, ocular examinations, video-oculography, visual evoked potentials, and retinal nerve fiber layer thickness were retrospectively reviewed. RESULTS: Twenty-two children were included (eight with asymmetric nystagmus and 14 with stable gaze). Subjects with asymmetric nystagmus presented at a younger age than those with stable gaze (2.0 vs 5.6 years; P < 0.001). None had neurofibromatosis type 1. Visual acuity, visual evoked potentials, nerve fiber layer, severity of optic atrophy, hydrocephalus, tumor volume, and tumor locations did not differ between those with asymmetric nystagmus and stable gaze. Asymmetric nystagmus resolved shortly after treatment, even though the average visual acuity did not improve. Changes in visual acuity or tumor volume were not different between those with asymmetric nystagmus and stable gaze after treatment. Eye movement recording from two subjects with asymmetric nystagmus revealed an asymmetric pendular-oscillation with vertical components. One subject with stable gaze developed asymmetric nystagmus with tumor growth into the rostral midbrain and associated unilateral vision loss. Another subject with tumor growth into the rostral midbrain acquired vertical saccade dysmetria. CONCLUSION: We hypothesize that asymmetric nystagmus associated with optic pathway gliomas is caused by subclinical abnormalities to retinal axons that connect to gaze holding centers in the rostral midbrain. Direct compression of the rostral midbrain was a possible factor to asymmetric nystagmus in some subjects. However, many subjects with stable gaze also show midbrain compression.

Retinal Findings in Young Children With Increased Intracranial Pressure From Nontraumatic Causes.

OBJECTIVES: Increased intracranial pressure (ICP) has been suggested in legal settings as an alternative cause of retinal hemorrhages (RHs) in young children who may have sustained abusive head trauma. We assessed the prevalence and characteristics of RHs in children with increased ICP. METHODS: We conducted a prospective, multicenter study of children <4 years old with newly diagnosed increased ICP as determined by using direct measurement and/or clinical criteria. Infants who were premature, neonates, and suspected survivors of abusive head trauma were excluded on the basis of nonocular findings. Fundus examinations were performed; extent, number, and type of RH in each of 4 distinct retinal zones were recorded. RESULTS: Fifty-six children (27 boys) were studied (mean age 15.4 months; range 1-43 months). All of the children had elevated ICP that required intervention. One child had papilledema. No child (0%; 95% confidence interval: 0%-6.4%) or eye (0%; 95% confidence interval: 0%-3.3%) was found to have an RH. Causes of increased ICP included hydrocephalus, intraventricular hemorrhage, congenital malformations, malfunctioning shunts, and the presence of intracranial space-occupying lesions. CONCLUSIONS: Although acute increased ICP can present in children with a pattern of peripapillary superficial RHs in the presence of papilledema, our study supports the conclusion that RHs rarely occur in the absence of optic disc swelling and do not present beyond the peripapillary area in the entities we have studied.

Clinical Outcomes in Children With Orbital Cellulitis and Radiographic Globe Tenting.

PURPOSE: Axial displacement of the globe with tenting centered on the optic nerve-globe junction is a predictor of visual loss in adults. The purpose of this study was to determine the visual outcomes of children with orbital cellulitis and globe tenting. METHODS: The records of 46 consecutive children with orbital cellulitis at a single tertiary children's hospital were reviewed retrospectively. Initial and final visual acuities were available for 34 of 46 patients (74%). Globe tenting was defined by an angle of 130° or less at the optic nerve-globe junction as derived from sagittal CT or MRI. Visual acuities of 4 children with globe tenting (mean age, 10.3 ± 3.3 years) were compared with those of 30 children without globe tenting (mean age, 10.8 ± 3.5 years). Final logarithm of the minimum angle of resolution visual acuities were analyzed. RESULTS: The mean posterior globe angle was 124.5° ± 8.0° in patients with globe tenting, compared with 145.6° ± 7.4° in the affected eye of the patients without globe tenting (p = 0.002). Final visual acuity was logarithm of the minimum angle of resolution = 0 following treatment in patients with globe tenting and logarithm of the minimum angle of resolution = 0.02 in patients without tenting (p = 0.70). DISCUSSION: We propose that the increased elastic compliance of the optic nerve sheath and sclera in children may contribute to better visual outcomes. CONCLUSIONS: Pediatric orbital cellulitis with globe tenting may not lead to devastating vision loss as previously seen in adults.

Bi-allelic mutations of CCDC88C are a rare cause of severe congenital hydrocephalus.

Congenital or infantile hydrocephalus is caused by genetic and non-genetic factors and is highly heterogeneous in etiology. In recent studies, a limited number of genetic causes of hydrocephalus have been identified. To date, recessive mutations in the CCDC88C gene have been identified as a cause of non-syndromic congenital hydrocephalus in three reported families. Here, we report the fourth known family with two affected individuals with congenital hydrocephalus due to a homozygous mutation in the CCDC88C gene identified by whole exome sequencing. Our two newly described children, as well as the previously published ones, all shared several features including severe infantile-onset hydrocephalus, mild to severe intellectual delay, varying degrees of motor delay, and infantile onset seizures. All identified homozygous mutations in CCDC88C abolish the PDZ binding site necessary for proper CCDC88C protein function in the Wnt signaling pathway. Our report further establishes CCDC88C as one of the few known recessive causes of severe prenatal-onset hydrocephalus. Recognition of this syndrome has important diagnostic and genetic implications for families identified in the future.

Does eye velocity due to infantile nystagmus deprive visual acuity development?

PURPOSE: To use eye movement recordings of young children to determine whether eye velocity from infantile nystagmus (IN) deprives the developing visual system of normal visual acuity. METHODS: The video-oculography recordings and visual acuity measurements (including Teller cards) of 15 children ≤6.0 years of age with IN without visual sensory disease (idiopathic IN) were reviewed retrospectively. Eye velocity that would limit visual acuity development was predicted from both empirical adult data adjusted for age and a temporal limitation model using published photoreceptor density data with age. Foveal alignment onto a target was measured in 5 subjects using confocal retinal imaging. RESULTS: All subjects had periods (85-2440 ms) during which eye velocity was below the limit that would reduce age-appropriate visual acuity. The percentage of time eye velocity was below the limit varied by 4%-54% across all eye movement recordings. Eye movement metrics (eye position variability, average eye velocity, maximum duration of foveation, and the nystagmus optimal foveation fraction) correlated poorly with age or with age-corrected visual acuity (r2 < 0.27 for each metric). Longitudinal visual acuity development overlapped between subjects with different nystagmus waveforms. CONCLUSIONS: Eye velocity was not predicted to completely deprive visual acuity development in subjects with idiopathic IN. Nystagmus may decrease visual acuity development in children with idiopathic IN by interfering with visual-cortical development in the context of increased visual noise due to image motion with imprecise foveation.

Optical Coherence Tomography in Optic Nerve Hypoplasia: Correlation With Optic Disc Diameter, Nerve Fiber Layer Thickness, and Visual Function.

BACKGROUND: The correlation between optic disc diameters (DDs) with average retinal nerve fiber layer thickness (RNFLT) and visual function in children with optic nerve hypoplasia (ONH) having nystagmus is unknown. METHODS: Data were obtained from a retrospective review of 28 children (mean age: 9.4 years; ±5.1). Optic DD was defined as the maximal horizontal opening of Bruch membrane with spectral optical coherence tomography combined with a confocal laser ophthalmoscope. Average RNFLT was obtained from circumpapillary b-scans. RNFLT was also remeasured at eccentricities that were proportionate with DD to rule out potential sampling artifacts. Visual function was assessed by visual acuity at last follow-up and by visual evoked potentials (VEP) in 11 patients. The eye with the larger DD, which had better visual acuity, was analyzed to exclude potential effects of amblyopia. RESULTS: DD was correlated with average RNFLT (r = 0.61), visual acuity (r = 0.32), and VEPs (r = 0.66). The relationship between RNFLT and DD was as follows: average RNFLT (µm) = 0.074 * DD (µm) - 18.8. RNFLT also correlated with the ratio of horizontal optic DD to macula-disc-margin distance (DD:DM; r = 0.59). RNFLT measured at eccentricities proportionate with DD showed progressive decrease in thickness only for DDs <1,100 µm. All patients with DD <1,000 µm had subnormal visual acuity, whereas those with DD <1,200 µm had subnormal VEPs. CONCLUSIONS: DD correlates with average RNFLT and with visual function in children with ONH. Using OCT imaging, DD can be obtained in children with nystagmus and provides objective information.

Enhanced retinal responses in Huntington's disease patients.

BACKGROUND: Huntington's disease (HD) is a fatal progressive neurodegenerative disease characterized by chorea, cognitive impairment and psychiatric symptoms. Retinal examination of HD patients as well as in HD animal models have shown evidence of retinal dysfunction. However, a detailed retinal study employing clinically available measurement tools has not been reported to date in HD. OBJECTIVE: The goal of this study was to assess retinal responses measured by electroretinogram (ERG) between HD patients and controls and evaluate any correlation between ERG measurements and stage of disease. METHODS: Eighteen patients and 10 controls with inclusion criteria of ages 18-70 years (average age HD subjects: 52.1 yrs and control subjects: 51.9 yrs) were recruited for the study. Subjects with previous history of retinal or ophthalmologic disease were excluded. Retinal function was examined by full-field ERG in both eyes of each subject. Amplitudes and latencies to increasing flash intensities in both light- and dark-adaptation were measured in all subjects. Statistical analyses employed generalized estimating equations, which account for repeated measures per subject. RESULTS: We analyzed the b-wave amplitudes of ERG response in all flash intensities and with 30 Hz flicker stimulation. We found statistically significant increased amplitudes in HD patients compared to controls at light-adapted (photopic) 24.2 and 60.9 cd.sec/m2 intensities, dark-adapted (scotopic, red flash) 0.22 cd.sec/m2 intensity, and a trend toward significance at light-adapted 30 Hz flicker. Furthermore, we found a significant increase in light-adapted ERG response from female compared to male HD patients, but no significant difference between gender amongst controls. We also noted a positive association between number of CAG repeats and ERG response at the smallest light adapted intensity (3.1 cd.sec/m2). CONCLUSIONS: ERG studies revealed significantly altered retinal responses at multiple flash intensities in subjects with an HD expansion allele compared to controls. Significant differences were observed with either light-adapted tests or the dark-adapted red flash which suggests that the enhanced responses in HD patients is specific to the cone photoreceptor pathway.

The relationship of nystagmus waveform on the VEP response in infantile nystagmus syndrome: a small case series.

PURPOSE: The relationship between eye movements and the visual evoked potential (VEP) response was examined in two subjects with infantile nystagmus syndrome (INS). Changes in VEP amplitude were compared between periods of foveation versus periods of high-frequency nystagmus. An analysis is proposed that improves extraction of the checkerboard reversal VEP signal from subjects with INS. METHODS: INS subjects were 2 healthy children (12-13 years old) with 20/40 or better corrected acuity. Optical coherence tomography confirmed the optic nerves, retina, and fovea were within normal variation. VEPs were recorded to checkerboard reversal and to onset/offset of horizontal gratings while simultaneously recording the electrooculogram (EOG). VEP epochs underwent Fourier analysis, and epochs were examined for phase consistency with the mean. Foveation periods were compared to video-oculography recordings from a separate session. RESULTS: Optic nerve misrouting, such as crossed VEP asymmetry seen in albinism, or ipsilateral VEP asymmetry seen in achiasma, was not detected in either subject. By averaging only epochs in which EOG epochs showed foveation, VEP amplitude could be increased ≥59%. Averaging the VEP only on epochs with consistent phase at Oz increased VEP amplitude by ≥twofold; subsequent EOG epochs after this analysis mostly contained foveation periods or minimal EOG activity. Latency varied <14 ms across all analyses. CONCLUSIONS: The checkerboard reversal VEP signal is dependent on foveation periods in subjects with INS despite good visual acuity. Reduction in VEP amplitude due to retinal image motion induces noise and/or lack of phase locking in the VEP epochs. Selective averaging of epochs based on phase consistency improves the extraction of a VEP signal, likely when retinal image motion is minimized.

VEP analysis methods in children with optic nerve hypoplasia: relationship to visual acuity and optic disc diameter.

PURPOSE: Assessing vision in young children with optic nerve hypoplasia (ONH) is challenging due to multi-directional infantile nystagmus, the range of optic nerve loss, and cognitive delay. This study examined visual evoked potential (VEP) responses and averaging techniques in children with ONH. The assumption is that EEG epochs with inconsistent temporal phase would be associated with nystagmus, signal reduction due to axon loss, and visual inattention. METHODS: A retrospective chart review was performed on 44 children (average age 2.2 years; SD 1.9). Optic disc diameter was estimated by ophthalmoscopy. Visual function was measured under binocular viewing and then compared to the eye with the larger optic disc to exclude secondary amblyopia. Visual acuity was measured by Teller cards or by recognition optotypes, and both measures were converted into log minimum angle of resolution (logMAR). VEPs were recorded to onset/offset of horizontal gratings and to reversing checkerboards. Signal-to-noise ratios (SNRs) were estimated from phase consistency across epochs in the Fourier domain. VEPs were also averaged after (1) correction of epochs for phase shifts across a limited bandwidth, or (2) selection of only epochs showing phase consistency. RESULTS: Optic disc diameter, logMAR, VEP amplitudes, and VEP SNR were all significantly inter-correlated. Optic disc diameter correlated best with VEP SNR (Spearman rho = 0.82; p < 0.001). Age-corrected logMAR correlated with optic disc diameter and VEP SNR (Spearman rho = -0.695 and 0.70, respectively; p < 0.001). VEP latency poorly correlated with optic disc diameter or logMAR. Correction of phase shifts or selection of epochs based on phase consistency significantly increased VEP amplitude and SNR for children with optic disc diameters <1000 microns. Correction of phase inconsistency did not improve the correlation of VEP parameters with optic disc diameter or with logMAR. CONCLUSIONS: In ONH, the size of the optic nerve is correlated with VEP SNR and logMAR. The results imply a direct relationship between the reduction in optic nerve axons and generalized reduction in visual function. Our calculation of VEP SNR provides objective assessment of optic nerve function that is independent of subjective scoring of VEP peaks.

Infantile Nystagmus and Abnormalities of Conjugate Eye Movements in Down Syndrome.

PURPOSE: Subjects with Down syndrome (DS) have an anatomical defect within the cerebellum that may impact downstream oculomotor areas. This study characterized gaze holding and gains for smooth pursuit, saccades, and optokinetic nystagmus (OKN) in DS children with infantile nystagmus (IN). METHODS: Clinical data of 18 DS children with IN were reviewed retrospectively. Subjects with constant strabismus were excluded to remove any contribution of latent nystagmus. Gaze-holding, horizontal and vertical saccades to target steps, horizontal smooth pursuit of drifting targets, OKN in response to vertically or horizontally-oriented square wave gratings drifted at 15°/s, 30°/s, and 45°/s were recorded using binocular video-oculography. Seven subjects had additional optical coherence tomography imaging. RESULTS: Infantile nystagmus was associated with one or more gaze-holding instabilities (GHI) in each subject. The majority of subjects had a combination of conjugate horizontal jerk with constant or exponential slow-phase velocity, asymmetric or symmetric, and either monocular or binocular pendular nystagmus. Six of seven subjects had mild (Grade 0-1) persistence of retinal layers overlying the fovea, similar to that reported in DS children without nystagmus. All subjects had abnormal gains across one or more stimulus conditions (horizontal smooth pursuit, saccades, or OKN). Saccade velocities followed the main sequence. CONCLUSIONS: Down syndrome subjects with IN show a wide range of GHI and abnormalities of conjugate eye movements. We propose that these ocular motor abnormalities result from functional abnormalities of the cerebellum and/or downstream oculomotor circuits, perhaps due to extensive miswiring.

Visual acuity and astigmatism in periocular infantile hemangiomas treated with oral beta-blocker versus intralesional corticosteroid injection.

BACKGROUND: Periocular infantile hemangiomas (PIH) can induce anisometropic astigmatism, a risk factor for amblyopia. Oral beta-blocker therapy has largely supplanted systemic or intralesional corticosteroids. The purpose of this study was to evaluate the effect and time course of these treatment modalities on visual acuity and induced astigmatism. METHODS: The medical records of patients with PIH treated with oral propanolol between November 2008 and July 2013 were retrospectively reviewed for data on visual acuity and astigmatism. Patients with incomplete pre- and post-treatment ophthalmic examinations were excluded. Results were compared to those of a similar cohort treated with intralesional corticosteroid injection. RESULTS: Mean astigmatism in affected eyes was 1.90 D before propranolol and 1.00 D after; patients showed a monophasic reduction in astigmatism over 12 months. By comparison, patients treated with corticosteroid injection showed a biphasic response, with an immediate steep decrease followed by a slow monophasic decline, paralleling propranolol-treated patients. Oral propranolol treatment caused a 47% reduction in mean induced astigmatism, less than the 63% reduction reported for the cohort treated with corticosteroid. No patient had visual acuity in the affected eye more than 1 standard devation below the age-matched norm, and none experienced significant side effects when treated with oral propranolol. CONCLUSIONS: In this patient cohort oral beta-blocker was well-tolerated. Treatment was therefore often initiated prior to the induction of significant astigmatism, with treatment effects comparable to steroid treatment. Visual outcomes were good. Early treatment may minimize the potential effect of astigmatism on postnatal visual development.

Visual sensory and ocular motor function in children with polymicrogyria: relationship to magnetic resonance imaging.

PURPOSE: To assess visual and ocular motor function in children with polymicrogyria (PMG). METHODS: The medical records of 15 children (0.4-4 years of age) with PMG documented by magnetic resonance imaging (MRI) and with age-corrected visual acuity measured by Teller acuity cards were reviewed retrospectively. Cortical function was assessed by pattern visually evoked potentials (VEP). Ocular motor function was assessed by video-oculography or clinical assessment. Results were compared to age-matched controls. RESULTS: Extent of PMG involvement varied from bilateral fronto-parietal to bilateral-diffuse. Nine children had involvement of the occipital lobe. Visual acuity at presentation was normal in 5 children (≥20/40 Snellen equivalent for age) and subnormal in 10 (average 20/200 equivalent). Visual acuity was similar in children with or without involvement of the occipital lobe (P = 0.4). Follow-up visual acuity was available for 9 children; 3 improved and 6 failed to improve (5 of whom had seizures). PMG involving the occipital lobe significantly reduced VEP amplitude and signal-to-noise ratios. Three infants without visually-guided behaviors had VEP responses. All 3 children with cytomegalovirus-related PMG without retinal disease had preserved visual function despite generalized MRI abnormalities. CONCLUSIONS: All children with PMG had recordable visual function either by visual acuity or VEP testing, however the majority did not show longitudinal improvement in acuity. Seizures may impose limits on visual acuity development. Children with cytomegalovirus-related PMG, microcephaly, and developmental delay can have normal visual acuity. Children with a recordable VEP but without visually guided behaviors may have a defect in sensorimotor transformation.