John P. Kelly

Longitudinal measures of visual function, tumor volume, and prediction of visual outcomes after treatment of optic pathway gliomas.

PURPOSEnTo examine longitudinal changes in visual acuity, tumor volume, and visual evoked potentials (VEP) before and after treatment in children with optic pathway gliomas.nnnDESIGNnRetrospective cohort study.nnnPARTICIPANTSnTwenty-one patients (0.7-9 years of age).nnnMETHODSnPatients initially were treated either by chemotherapy (n = 18) or radiotherapy (n = 3). Patients were followed up with serial magnetic resonance imaging, age-corrected visual acuity measurements in logarithm of the minimum angle of resolution (logMAR) units, and pattern VEP. Longitudinal visual outcome data were obtained on average for 9 years (range, 4-16 years). Tumor volumes before and after treatment were estimated in 15 patients. Multivariate regression was used to predict visual outcomes.nnnMAIN OUTCOME MEASURESnVisual acuity, relative tumor volumes, and VEP.nnnRESULTSnBefore treatment, 81% of patients had reduced visual acuity and 81% had optic nerve pallor, whereas all had a reduced VEP in 1 or both eyes. After initial treatment, tumor volume decreased in 53%, stabilized in 27%, and progressively increased in 20%. Treatment arrested the rapid decline in visual acuity loss and stabilized visual acuity for 4 to 5 years. The rate of visual acuity decline was not correlated with tumor shrinkage. Sixty-two percent of patients required additional treatment with either chemotherapy or radiation because of tumor growth or progressive loss of visual function. Visual acuity at last examination was stable or improved in 33% of patients, but on average declined 0.4 logMAR units. Visual acuity was 20/200 or better in 1 eye of 62% of patients. The rate of visual acuity decline was predicted weakly by tumor volume at presentation (R(2) = 0.19; P<0.009). Visual acuity at last examination was predicted best by visual acuity and tumor volume at presentation (R(2) = 0.66; P<0.001).nnnCONCLUSIONSnSystemic chemotherapy arrested the decline in visual acuity and stabilized vision on average for 5 years. At presentation, VEPs were a more sensitive indicator of optic pathway damage than visual acuity or optic nerve appearance. Although tumor reduction or stabilization was achieved in 80% of patients, pre-existing visual damage, indexed by objective measures of tumor volume and visual function, limited visual outcomes.nnnFINANCIAL DISCLOSURE(S)nThe author(s) have no proprietary or commercial interest in any materials discussed in this article.

Fatal paroxysmal tachycardia associated with focal myocarditis of the Purkinje system in a 14-month-old girl

A fatal case of paroxysmal tachycardia associated with focal myocarditis of the Purkinje system is described. A viral tropism for the muscle cells of the Purkinje system is postulated.

Crouzon Syndrome: Relationship of Rectus Muscle Pulley Location to Pattern Strabismus

PURPOSEnInvestigate the relationship between the extorsion of the rectus muscle pulleys and the V-pattern exotropia and overelevation in adduction observed in Crouzon syndrome.nnnMETHODSnTwenty children with Crouzon syndrome had assessment of eye alignment. The horizontal and vertical positions of the four rectus muscle pulleys were estimated from coronal CT images. Eye alignment was simulated in Orbit 1.8 software by shifting the corresponding location of the rectus muscle pulley array.nnnRESULTSnEleven of the 20 patients had a V-pattern exotropia with displacements of each rectus muscle pulley ranging from 2 to 7 mm. The remaining nine patients were orthotropic with <2 mm displacement of the rectus muscle pulleys. Simulated displacements (>2 mm) of either the horizontal or vertical rectus muscle pulleys produced a similar strabismus pattern. The amount of V-pattern exotropia observed clinically was highly correlated with the amount predicted by pulley displacements in Orbit 1.8 (r(2) = 0.63; P < 0.0001). The displacement of vertical and horizontal rectus muscle pairs was significantly higher for patients having overelevation in adduction.nnnCONCLUSIONSnRotation of the four rectus muscle pulleys relative to the corresponding rotation planes of the globe changes the direction and magnitude of their active and passive pulling forces in a gaze-dependent manner. Extorsion of the horizontal and vertical rectus muscle pulleys in Orbit 1.8 reproduces the pattern strabismus observed in Crouzon syndrome. The high correlation between the predicted magnitude of the V-pattern exotropia and observed exotropia indicates that extorsion of the rectus muscle pulleys primarily accounts for the pattern strabismus.

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

PURPOSEnSubjects 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).nnnMETHODSnClinical 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.nnnRESULTSnInfantile 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.nnnCONCLUSIONSnDown 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.

Waveform variance and latency jitter of the visual evoked potential in childhood

PurposeRecording the visual evoked potential (VEP) in young children is challenging due to movement artifacts with variable fixation or attention. This study examined the effects of latency jitter, noise, and waveform consistency on the averaging of the VEP across childhood age.MethodsStimuli were contrast-reversing (1.4xa0Hz) checkerboards of 163xa0arcxa0minutes and pattern-onset-offset of 0.5 cycle/degree horizontal sine-wave gratings. Subjects were 79 normal children (0.3–16xa0years age; mean 6.9). Results were compared to recordings of EEG noise only (noise controls). Epochs underwent four averaging methods: (1) latency jitter correction using cross-correlation, (2) correction of phase shifts across a limited bandwidth in the Fourier domain, (3) selection of epochs based on consistency in the time domain, and (4) selection of epochs based on phase consistency in the Fourier domain. Signal-to-noise ratios (SNR) were estimated in both the time and Fourier domains.ResultsCompared to standard averaging, all methods improved the amplitude of the primary peak (P100) while generating mild changes in latency. All methods also increased amplitudes of residual peaks in noise controls. In VEPs with an adequate SNR, selective averaging in the Fourier domain provided the greatest improvement in amplitude (61xa0% increase; pxa0<xa00.0001) without prolongation in latency. Correction of latency jitter did not consistently improve amplitude but caused latency prolongation in 24xa0% of subjects. There was no age-related effect of any averaging method for either stimulus.ConclusionsSince latency jitter correction does not improve VEP amplitude more than selective averaging, recording artifacts in children are dominated by random phase components rather than inducing latency jitter.

Occlusion therapy improves phase-alignment of the cortical response in amblyopia.

The visual evoked potential (VEP) generated by the amblyopic visual system demonstrates reduced amplitude, prolonged latency, and increased variation in response timing (phase-misalignment). This study examined VEPs before and after occlusion therapy (OT) and whether phase-misalignment can account for the amblyopic VEP deficits. VEPs were recorded to 0.5-4cycles/degree gratings in 10 amblyopic children (2-6years age) before and after OT. Phase-misalignment was measured by Fourier analysis across a limited bandwidth. Signal-to-noise ratios (SNRs) were estimated from amplitude and phase synchrony in the Fourier domain. Responses were compared to VEPs corrected for phase-misalignment (individual epochs shifted in time to correct for the misalignment). Before OT, amblyopic eyes (AE) had significantly more phase-misalignment, latency prolongation, and lower SNR relative to the fellow eye. Phase-misalignment contributed significantly to low SNR but less so to latency delay in the AE. After OT, phase-alignment improved, SNR improved and latency shortened in the AE. Raw averaged waveforms from the AE improved after OT, primarily at higher spatial frequencies. Correcting for phase-misalignment in the AE sharpened VEP peak responses primarily at low spatial frequencies, but could not account for VEP waveform improvements in the AE after OT at higher spatial frequencies. In summary, VEP abnormalities from the AE are associated with phase-misalignment and reduced SNR possibly related to desynchronization of neuronal activity. The effect of OT on VEP responses is greater than that accounted for by phase-misalignment and SNR alone.

Evaluation and treatment of failed nasolacrimal duct probing in Down syndrome

PURPOSEnTo elucidate the mechanisms underlying failed nasolacrimal duct (NLD) probing in children with Down syndrome (DS) utilizing computed tomography (CT) scans and histopathology of nasal mucosa.nnnMETHODSnThe medical records of children with DS and NLD obstruction confirmed by dye disappearance testing who failed NLD surgery were retrospectively reviewed. Dimensions of the bony NLD and presence of postductal mucosal obstruction were obtained from CT scans. Histopathology of the nasal mucosa was performed in a subset of patients. Subsequent treatment was topical or intranasal corticosteroids or submucosal corticosteroids alone or combined with surgical reduction of the inferior turbinate.nnnRESULTSnA total of 9 subjects (age range, 8-10 years) and 43 age-matched controls were included. Both groups demonstrated a logarithmic increase in NLD and maxilla dimensions with increasing age; however, the transverse diameter of the NLD was consistently 1-2 mm smaller in children with DS ≤5 years age (n = 4) than in age-matched controls. The transverse diameter in DS children overlapped that of controls after 5 years age. Histopathology revealed abnormal lymphoplasmacytic inflammation of the mucosa in 4 of 5 biopsies of DS patients, consistent with chronic infection, allergic disease, or immune dysregulation. The postductal obstruction was successfully treated with topical or intranasal corticosteroids or by surgical reduction of the inferior turbinate submucosa with corticosteroid injection.nnnCONCLUSIONSnBefore 5 years of age, NLD obstruction in children with DS was associated with reduced dimensions of the NLD and hypertrophic nasal mucosa. In DS children older than 5 years of age, the dimensions of the NLD are normal and postductal obstruction due to hypertrophic nasal mucosa should be considered.

Anatomic features and function of the macula and outcome of surgical tenotomy and reattachment in achiasma.

OBJECTIVEnTo examine the anatomic features and function of the macula in achiasma and to compare visual acuity, eye movements, foveation, and eye velocity before and after tenotomy and reattachment (T&R) surgery.nnnDESIGNnCase series.nnnPARTICIPANTSnTwo children with isolated achiasma.nnnMETHODSnOphthalmologic examinations, brain magnetic resonance imaging, full-field and multifocal electroretinography (ERG), visual evoked potentials (VEPs), spectral-domain optical coherence tomography (OCT), eye-movement recordings, and unilateral T&R in 1 patient.nnnMAIN OUTCOME MEASURESnVisual acuity before and after surgery, macular anatomic features and function, and eye velocity before and after T&R surgery in 1 patient.nnnRESULTSnMagnetic resonance imaging and VEP confirmed absence of decussation of retinofugal fibers in both patients. Visual acuity was 20/100 and 20/200. The anatomic features and function of the fovea and macula were normal by OCT and multifocal ERG. After T&R, there was a marked reduction in horizontal eye velocity and monocular visual acuity improved to 20/80.nnnCONCLUSIONSnThe finding that the macula is normal in achiasma suggests that reduced acuity is the result of retinal image motion from nystagmus. Two-muscle T&R reduces horizontal retinal image motion and can improve visual acuity in achiasma or patients with infantile nystagmus.

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

PURPOSEnTo assess visual and ocular motor function in children with polymicrogyria (PMG).nnnMETHODSnThe medical records of 15 children (0.4-4xa0years 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.nnnRESULTSnExtent 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 (Pxa0=xa00.4). Follow-up visual acuity was available for 9 children; 3 improved and 6 failedxa0to 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.nnnCONCLUSIONSnAll 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.