Optic Atrophy and Inner Retinal Thinning in CACNA1F-related Congenital Stationary Night Blindness.

Hemizygous pathogenic variants in CACNA1F lead to defective signal transmission from retinal photoreceptors to bipolar cells and cause incomplete congenital stationary night blindness in humans. Although the primary defect is at the terminal end of first-order neurons (photoreceptors), there is limited knowledge of higher-order neuronal changes (inner retinal) in this disorder. This study aimed to investigate inner retinal changes in CACNA1F-retinopathy by analyzing macular ganglion cell layer-inner plexiform layer (GCL-IPL) thickness and optic disc pallor in 22 subjects with molecularly confirmed CACNA1F-retinopathy. Detailed ocular phenotypic data including distance and color vision, refraction and electroretinogram (ERG) were collected. Distance vision was universally reduced (mean: 0.42 LogMAR), six had abnormal color vision and myopia was common (n = 15; mean: -6.32 diopters). Mean GCL-IPL thickness was significantly lower in patients (55.00 µm) compared to age-matched controls (n = 87; 84.57 µm; p << 0.001). The GCL-IPL thickness correlated with scotopic standard (p = 0.04) and bright-flash (p = 0.014) ERG b/a ratios and photopic b-wave amplitudes (p = 0.05). Twenty-one patients had some degree of disc pallor (bilateral in 19). Fifteen putative disease-causing, including five novel variants were identified. This study establishes macular inner retinal thinning and optic atrophy as characteristic features of CACNA1F-retinopathy, which are independent of myopia and could impact potential future treatment strategies.

Long-term follow-up of torsional augmentation surgery in a case of congenital ocular tilt reaction with head tilt.

Torsional augmentation surgery was used to correct the anomalous head position (AHP) in a child with congenital ocular tilt reaction (OTR). The underlying neuropathology was hypoplasia involving the right hemicerebellum and contralateral brainstem. Postoperatively there was an acceptable and variable resolution of head tilt sustained over a 25-year follow-up period. These findings suggest that early torsional augmentation surgery can effectively correct stable OTR head tilt in congenital cases over the long term.

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.

Pediatric orbital cellulitis in the Haemophilus influenzae vaccine era.

PURPOSE: To evaluate the microbiology of pediatric orbital cellulitis in blood cultures and abscess drainage cultures following the introduction of the Haemophilus influenzae serotype b (Hib) vaccine. METHODS: The medical records of all pediatrics patients (aged <18 years) at a tertiary pediatric hospital during the period January 2000 to July 2011 with a computed tomography orbital imaging querying "orbital cellulitis," "periorbital cellulitis," "preseptal cellulitis," or "post-septal cellulitis" were retrospectively reviewed. The records, microbiology, and radiology of these patients were reviewed to assess the rates and complications of H. influenzae orbital cellulitis, including bacteremia and meningitis. RESULTS: A total of 149 patients were diagnosed with preseptal or orbital cellulitis, of whom 101 (mean age, 7.2 ± 4.0) had true orbital cellulitis. No patients grew H. influenzae from blood cultures. Of the 101 patients, 30 (29.7%) required surgical drainage and had abscess drainage fluid sent for microbiology. Of these, 18 (64.3%) had a positive culture: 4 (13.3%) grew H. influenzae from their abscess drainage fluid samples; 1 grew H. influenzae alone; and 3 had mixed growth that included H. influenzae. The patients positive for H. influenzae were significantly older and had significantly larger abscesses. CONCLUSIONS: Although there were no cases of H. influenzae bacteremia or meningitis in our cases of orbital cellulitis, abscess drainage fluid microbiology indicated that H. influenzae remains a cause of orbital cellulitis. H. influenzae abscess volume was significantly larger than other bacterial abscesses and was associated with abscesses of mixed bacterial growth in older children.

Functional-structural correlations in the afferent visual pathway in pediatric demyelination.

OBJECTIVE: We evaluated the relationship of optical coherence tomography (OCT)-measured ganglion cell layer (GCL) and retinal nerve fiber layer (RNFL) thickness to other functional measures of afferent visual pathway competence including high-contrast visual acuity (HCVA) and low-contrast visual acuity (LCVA), visual field sensitivity, and color vision perception in a pediatric population with demyelinating disorders. METHODS: This was a cross-sectional evaluation of 37 children, aged 8-18 years, with pediatric demyelinating disorders (n = 74 eyes), and 18 healthy controls (n = 36 eyes), who were recruited from the University of Toronto, Hospital for Sick Children and the University of Calgary, Alberta Children's Hospital, Canada. A standardized visual battery, including spectral-domain OCT, visual fields, LCVA, and HCVA, was performed in all subjects. RESULTS: Mean RNFL thickness was 26 µm (25.6%) lower in patients with demyelination (76.2 µm [3.7]) compared to controls (102.4 µm [2.1]) (p < 0.0001). Mean GCL thickness was 20% lower in patients as compared to controls (p < 0.0001). Mean GCL and RNFL thickness were strongly correlated (r = 0.89; p < 0.0001), yet in contrast to RNFL thickness, no differences in GCL thickness were noted between optic neuritis (ON) eyes and non-ON eyes of patients. HCVA and LCVA and visual field mean deviation scores decreased linearly with lower RNFL thickness. CONCLUSION: GCL thickness was decreased in patients regardless of history of ON. The retina may be a site of primary neuronal injury in pediatric demyelination.

The effect of adding orbital computed tomography findings to the Chandler criteria for classifying pediatric orbital cellulitis in predicting which patients will require surgical intervention.

PURPOSE: To assess the effect of adding orbital computerized tomography (CT) findings to the Chandler criteria for classifying pediatric orbital cellulitis in predicting which patients will require surgical intervention. METHODS: The medical records of patients with orbital CT at a tertiary pediatric hospital from January 2000 to March 2011 were reviewed retrospectively. CT images of cases with radiology report of postseptal orbital involvement were further reviewed by a neuroradiologist. RESULTS: Of 101 cases of orbital cellulitis, 71 (mean age, 7.1 ± 4.0) were successfully managed with systemic antibiotics alone; 30 patients (mean age, 7.2 ± 4.3) required surgical intervention. Bony destruction on CT was significantly associated with surgical intervention (P = 0.02), and the size of the subperiosteal abscess (SPA) was significantly correlated with management outcome. Patients who were managed with systemic antibiotics alone had a mean SPA volume of 2.1 ± 2.4 mL; those who had undergone surgical intervention had a mean SPA volume of 14.3 mL ± 16.8 mL (P < 0.0001). If SPA volume is <3.8 mL, then the probability of surgery is 12%; if SPA is >3.8 mL, the probability of surgery is 71% (P < 0.0001). CONCLUSIONS: Adding radiological characteristics such as presence of bony destruction on CT and size of SPA to the Chandler orbital cellulitis classification scheme increases the ability to more accurately predict which patients will require surgical intervention.

The optic disc is minimal in children with idiopathic intracranial hypertension.

This study sought to characterize the optic disc morphology, particularly the cup-to-disc ratio of the optic nerve head in children with idiopathic intracranial hypertension. The medical charts and digital optic disc photos of children with confirmed diagnosis of idiopathic intracranial hypertension were reviewed retrospectively. The optic disc area, cup area, and cup-to-disc ratio were measured digitally using VISUPAC software, and the mean values of those parameters were compared to the published norms. Of children with idiopathic intracranial hypertension, 83% had absence of the physiological cup of the optic disc, compared to 10% of children in the general population of the same age. The median disc area was 2.2 mm(2), and median cup area was 0.0mm(2), compared to the published norms of 2.69 mm(2) and 0.44 mm(2), respectively. There is very significantly high prevalence of small optic disc cups in children with idiopathic intracranial hypertension, with the cup being absent on majority of cases in our patient cohort. This may signal an underlying systemic predisposition to the development of intracranial hypertension.

Transient visual loss and isolated disk edema in juvenile nasopharyngeal angiofibroma.

Juvenile nasopharyngeal angiofibroma is a well-described but rare benign tumor that mainly affects adolescent boys. Although it is capable of extravagant local extension and tissue destruction, the tumor is amenable to effective therapy. Ocular or visual complications have been little noted in the literature. We report a case whose sole symptom was unilateral transient visual impairment and findings were limited to a nonspecific optic disk edema.

Ocular manifestations of the Johanson-Blizzard syndrome.

Johanson-Blizzard syndrome is a rare autosomal-recessive congenital disorder characterized by hypoplastic nasal alae, midline scalp defects, deafness, microcephaly, hypothyroidism, absent permanent teeth, malabsorption, and failure to thrive. The literature was reviewed to define the reported spectrum of ocular manifestations, which are not well documented. We found that nasolacrimal system malformations are a common feature of Johanson-Blizzard, whereas intraocular malformations are rare. This report describes the ophthalmologic findings and management of 2 affected children.

Natural history and outcome of optic pathway gliomas in children.

BACKGROUND: The optimal management of optic pathway gliomas (OPGs) is complicated by their variable natural history, the association with neurofibromatosis type 1 (NF1) and difficulties in defining progression and response to treatment. METHODS: This study is a retrospective review of all children presenting to a single institution with an OPG between 1990 and 2004. RESULTS: Of the 133 children included, 78 (59%) had NF1; 87 (71 NF1) were observed initially, of whom 23 (11 NF1) subsequently required treatment. Forty-six patients received immediate treatment. Initial treatment, without or with an observation period, comprised chemotherapy alone (32, 11 NF1); debulking + chemotherapy (15, 4 NF1); gross total resection (6); radiotherapy (2); debulking + radiotherapy (3); and debulking only (12, 3 NF1). Overall, 16 patients were irradiated during the study period. Four children died (overall survival at 5 and 10 years was 97.6% and 94.6% for those who required treatment). Progression-free survival (PFS) for the 69 patients who needed treatment was 48%. There was no difference in PFS between chemotherapy versus chemotherapy + debulking or debulking alone. PFS for the NF1 patients who required treatment was similar to that of non-NF1 patients. Mean follow-up time was 9.0 (range 0.6-18.0, median 8.6) years. CONCLUSIONS: The study confirms the complexity of OPGs and that NF1 is a major determinant of the resultant behavior of the tumor.

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.

Head position-dependent changes in ocular torsion and vertical misalignment in skew deviation.

OBJECTIVES: To investigate whether ocular torsion and vertical misalignment differ in the upright vs supine position in skew deviation and to compare these findings with those in trochlear nerve palsy. METHODS: Ten patients with skew deviation, 14 patients with unilateral peripheral trochlear nerve palsy, and 12 healthy subjects were prospectively recruited. With subjects first in the upright position and then in the supine position, ocular torsion was measured by double Maddox rods and vertical misalignment was measured by the prism and alternate cover test. RESULTS: In patients with skew deviation, the abnormal torsion and vertical misalignment in the upright position decreased substantially with change to the supine position, whereas in patients with trochlear nerve palsy, it changed little between positions. Torsion was decreased by 83% in patients with skew deviation, 2% in patients with trochlear nerve palsy, and 6% in healthy subjects (P < .001). Similarly, vertical misalignment was decreased by 74% in patients with skew deviation and increased by 5% in patients with trochlear nerve palsy and 6% in healthy subjects (P < .001). CONCLUSIONS: Our findings provide the basis for additional clinical tests to support the classic 3-step test: ocular torsion and vertical misalignment that decrease from the upright position to the supine position indicate skew deviation, whereas torsion and vertical misalignment that do not change significantly between positions indicate trochlear nerve palsy.

Dissociated vertical deviation in patients with intermittent exotropia.

PURPOSE: To determine whether the age of strabismus onset and the degree of stereopsis are related to the development of dissociated vertical deviation (DVD) in patients with intermittent exotropia and to describe the characteristics of DVD in patients with intermittent exotropia and DVD. METHODS: Retrospective record review of patients with (1) intermittent exotropia with DVD; (2) infantile esotropia with DVD; and (3) intermittent exotropia without DVD. Age of strabismus onset, stereopsis, strabismus measurements, and the response of DVD to the Bielschowsky head-tilt test were compared among the three groups. RESULTS: Fifty-two children with intermittent exotropia and DVD were identified. In patients with intermittent exotropia with DVD and intermittent exotropia without DVD group, the mean age of strabismus onset was 12.7 months and 28.9 months, respectively (p = 0.03), and mean stereopsis was 147 arcsec and 65 arcsec (p = 0.02). In patients with intermittent exotropia with DVD and infantile esotropia with DVD, the mean amount of DVD was 9.7(Delta) and 17.2(Delta), respectively (p < 0.01). Bielschowsky head-tilt test showed an increase of DVD on ipsilateral head tilt in 91% and 63.3%, respectively. CONCLUSIONS: Intermittent exotropia with DVD is characterized by earlier onset of strabismus and worse stereopsis, suggesting that these factors may be related to the development of DVD in patients with intermittent exotropia. Unlike DVD in infantile esotropia, DVD in intermittent exotropia was smaller in amount and demonstrated a more uniform response to the Bielschowsky head-tilt test.

Evaluation of vertical rectus muscles using ultrasound biomicroscopy.

PURPOSE: To evaluate the accuracy of ultrasound biomicroscopy (UBM) in measuring the distance (in mm) from limbus to the insertion of vertical rectus muscles (superior rectus and inferior rectus compared with the "gold standard" surgical caliper at the time of surgery. METHODS: Prospective, masked, observational study of 31 vertical rectus muscle insertions in which we compared the measurements from the limbus as measured by 50 MHz UBM, either preoperatively or at the time of anesthesia, with that measured by surgical caliper intraoperatively. Measurements (UBM and surgical) were evaluated by two different observers and analyzed using the Bland-Altman method. All UBM measurements were done by the same author. The intraclass correlation coefficient (ICC) and Pearson coefficient with 95% confidence intervals were used to quantify the degree of agreement between the two methods. RESULTS: Thirty-one vertical muscles were evaluated (13 superior rectus and 18 inferior rectus, of which 7 muscles were reoperations). The average for UBM measurements was 6.63 mm and for surgical caliper was 7.09 mm. The measurements for the two methods were all within +/-2 standard deviations of the mean. Only three measurements showed differences more than 1 mm. The ICC was 0.78 and Pearson coefficient was 0.85, indicating a "very good" correlation between the two methods. The longest distance from the limbus that could be accurately measured with the UBM was 12 mm. In one case a pseudotendon was differentiated from the true insertion of a previously recessed superior rectus muscle. CONCLUSIONS: The UBM and surgical measurements showed "very good" correlation when allowing for a margin of error of +/-1.0 mm between the two modalities, indicating that the UBM is a good predictor of the position of the vertical rectus muscles.

Obstructive sleep apnea syndrome with bilateral papilledema and vision loss in a 3-year-old child.

We describe bilateral papilledema and vision loss in a 3-year-old child with obstructive sleep apnea. Although lumbar puncture initially disclosed a normal opening pressure, cerebrospinal fluid (CSF) pressure monitoring during sleep confirmed intermittent episodes of elevated intracranial pressure corresponding to increased airway resistance. The association of obstructive sleep apnea and raised intracranial pressure is recognized in children with craniosynostosis but has not been reported in its absence.

Assessment of chemotherapeutic response in children with proptosis due to optic nerve glioma.

INTRODUCTION: Some children with optic pathway gliomas present with proptosis related to intraorbital tumor extension. The radiological assessment of chemotherapeutic response in these patients can be complicated by irregular tumor shape and lack of relation between tumor volume and cosmetic effect. METHOD: We propose that proptosis measurements and derivation of a proptosis index can be a useful adjunct to the measurement of tumor volume in the radiological assessment of chemotherapeutic response. The proptosis index was derived as the ratio of the difference in proptosis between eyes postchemotherapy to that prechemotherapy. A series of six patients with proptosis and the diagnosis of an optic nerve tumor from an optic pathway glioma registry demonstrate by case example the correlation between the proptosis index and the clinical and radiographic response to chemotherapy. CONCLUSIONS: We have found that a proptosis index <1 correlates with a chemotherapeutic maintained response and an index >1 correlates with progressive disease.

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.