An unexpected turn: a case of torsional anomalous retinal correspondence after myectomy of previously anteriorized inferior oblique muscles in a child.

We report a case of torsional diplopia caused by presumed torsional anomalous retinal correspondence after myectomy of previously asymmetrically anteriorized inferior oblique muscles for inferior oblique overaction. Given this patient's experience, it may be prudent to operate with caution on previously anteriorized inferior oblique muscles, especially when anteriorization is performed at a very young age.

Comparison of Eye Tracking and Teller Acuity Cards for Visual Acuity Assessment in Pediatric Cortical/Cerebral Visual Impairment.

PURPOSE: To compare eye tracking and Teller acuity cards (TAC) for assessment of visual acuity in children with cortical, or cerebral, visual impairment (CVI). DESIGN: Reliability and validity study. METHODS: We recruited 41 children with CVI from a single academic pediatric neuro-ophthalmology clinic. All children performed eye tracking to measure visual acuity, and 26 children completed TAC assessment by a masked examiner. Additionally, 2 pediatric neuro-ophthalmologists graded visual behavior using the 6-level Visual Behavior Scale (VBS). Eye tracking and TAC were performed at baseline and at 1 month. Test-retest reliability of eye tracking and TAC were assessed using the intraclass correlation coefficient (ICC). Eye tracking and TAC visual acuities were correlated with one another and VBS scores using the Spearman correlation coefficient. RESULTS: Test-retest reliability was excellent for eye tracking measurement of visual acuity (ICC = 0.81, P < .0001). For pediatric CVI, TAC test-retest reliability was fair (ICC = 0.42, P = .04). There was a moderate correlation between eye tracking and TAC (r = 0.43, P = .03) and between TAC and VBS score (r = 0.50, P = .009), and a strong correlation between eye tracking grating acuity and VBS score (r = 0.72, P < .0001). CONCLUSIONS: In our cohort of children with CVI, grating acuity measured by eye tracking demonstrated higher test-retest reliability and stronger correlation with pediatric neuro-ophthalmologic assessment of visual behavior than Teller acuity. Objective determination of gaze direction by an eye tracking camera may be more accurate than human assessment in this population. Future research is needed to determine the optimal methods of longitudinal assessment of visual function and functional vision in children with CVI.

The Nictavi Tarsus Patch: A New Device for Achieving Temporary Eyelid Closure in Lagophthalmos.

Purpose: To evaluate the effectiveness, tolerability, and safety of the Nictavi Tarsus Patch™ (NTP) in inducing temporary eyelid closure for the management of lagophthalmos in the pediatric and young adult population. Methods: We prospectively enrolled 20 patients <21 years of age who had previously been managed for lagophthalmos to trial the NTP in clinic. Inter-palpebral fissure distance (IPFD) was compared before and after the placement of the NTP in the eyes-closed position using paired t-tests. Subjects then underwent a 3-night home trial with the NTP, and parent and subject perceptions of effectiveness, comfort, and complications with the patch were analyzed using Likert scale survey questions. Results: Twenty subjects ages 2-20 years with paralytic (65%) and non-paralytic (35%) lagophthalmos were enrolled. The NTP improved lagophthalmos from a mean pre-placement IPFD of 3.3 mm to post-placement IPFD of 0.4 mm (p < 0.01). Overall, 80% of subjects achieved successful eyelid closure defined as ≤1 mm of post-placement IPFD. When stratified by subtype, 100% of subjects with paralytic lagophthalmos achieved successful eyelid closure compared to 71% of subjects with non-paralytic lagophthalmos. On a scale of 1 (worst) to 5 (best), parents rated the NTP at 4.3±0.7 for comfort while wearing, 4.3±1.0 for comfort in removing, 4.6±0.7 for ease of use, and 4.3±0.9 for effectiveness. Ninety-three percent of parents reported preferring NTP to other eyelid closure methods previously tried and indicated that they would use it again. Conclusion: The NTP is an effective, tolerable, and safe method of eyelid closure for children and young adults.

Association of prepregnancy body mass index and gestational weight gain on severity of optic nerve hypoplasia.

BACKGROUND: Optic nerve hypoplasia (ONH) is a birth defect of unknown etiology and a leading cause of visual impairment in developed countries. Recent studies suggest that factors of deprivation and exposures of poor nutritional status, such as lower gestational weight gain (GWG), may be associated with increased risk of ONH. The present study describes the prenatal features of mothers of ONH cases, including prepregnancy BMI and GWG, and the associations with clinical features of disease severity. METHODS: Retrospective study of prenatal records for cases of ONH enrolled in a research registry. Prepregnancy BMI and GWG were compared to maternal characteristics and clinical findings of ONH severity including bilaterality, hypopituitarism, and neuroradiographic abnormalities. RESULTS: Compared to population-based normative data of births in the United States, mothers of ONH cases (n = 55) were younger (23.3 vs. 25.8 years; p = 0.03), with higher incidence of inadequate GWG (34.0% vs. 20.4%; p = 0.03) predominantly in the first and second trimesters. The presence of major brain malformations was associated with younger maternal age (21.6 [IQR 19.4, 24.7] vs. 24.9 years [IQR 22.1, 28.5] [p = 0.02]), primiparity (44.1% vs. 13.3%; p = 0.05) and decreased prepregnancy BMI (20.9 kg/m2 [19, 22.5] vs. 25.5 kg/m2 [21.3, 28.2]; p < 0.01). CONCLUSION: Decreased prepregnancy BMI and inadequate GWG correlated with clinical features of ONH severity, specifically bilateral disease and presence of major brain malformations.

Full-field Scotopic Threshold Improvement after Voretigene Neparvovec-rzyl Treatment Correlates with Chorioretinal Atrophy.

PURPOSE: To analyze demographic and ophthalmic data in patients with and without chorioretinal atrophy after voretigene neparvovec-rzyl (VN) to identify possible causes for this phenomenon. DESIGN: Retrospective cohort study with longitudinal follow-up. PARTICIPANTS: A total of 71 eyes of 38 patients aged 2 to 44 years with RPE65-mediated retinal dystrophy treated with VN across 2 large gene therapy centers in the United States and Germany. METHODS: Patients treated with VN who developed atrophy were compared with those who did not. MAIN OUTCOME MEASURES: Gender, age, surgical center, spherical equivalent refraction, best-corrected visual acuity (BCVA), baseline full-field scotopic threshold testing (FST), and posttreatment change in FST. RESULTS: A total of 20 eyes of 12 patients developed atrophy after treatment with VN (28% of all eyes). There was no significant difference in gender, age, surgical center, or spherical equivalent refraction between the atrophy group and the no atrophy group. However, patients between school age and young adulthood were predominantly affected, whereas the youngest and the oldest patients did not develop atrophy. Baseline BCVA was better in patients who developed atrophy than those who did not (P = 0.006). The postoperative improvement in FST at 1 month was significantly higher in the atrophy group than in the no atrophy group (P = 0.0005), and this difference remained statistically significant at 1 year (P = 0.0001). There was no correlation to baseline FST, to inflammation, or to which eye was treated first. CONCLUSIONS: The degree of FST improvement after VN appears to be strongly correlated with the development of VN-related chorioretinal atrophy. This finding raises the possibility that atrophy may develop as a toxic or metabolic sequela of vector-mediated RPE65 expression. In light of the expanding number of retinal gene therapy clinical trials, this complication warrants further study because it may not be limited to VN. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

The Pediatric Optic Neuritis Prospective Outcomes Study: Two-Year Results.

PURPOSE: Pediatric optic neuritis (ON) is a rare disease that has not been well characterized. The Pediatric ON Prospective Outcomes Study (PON1) was the first prospective study to our knowledge aiming to evaluate visual acuity (VA) outcomes, including VA, recurrence risk, and final diagnosis 2 years after enrollment. DESIGN: Nonrandomized observational study at 23 pediatric ophthalmology or neuro-ophthalmology clinics in the United States and Canada. PARTICIPANTS: A total of 28 (64%) of 44 children initially enrolled in PON1 (age 3-<16 years) who completed their 2-year study visit. METHODS: Participants were treated at the investigator's discretion. MAIN OUTCOMES MEASURES: Age-normal monocular high-contrast VA (HCVA). Secondary outcomes included low-contrast VA (LCVA), neuroimaging findings, and final diagnoses. RESULTS: A total of 28 participants completed the 2-year outcome with a median enrollment age of 10.3 years (range, 5-15); 46% were female, and 68% had unilateral ON at presentation. Final 2-year diagnoses included isolated ON (n = 11, 39%), myelin oligodendrocyte glycoprotein-associated demyelination (n = 8, 29%), multiple sclerosis (MS) (n = 4,14%), neuromyelitis optica spectrum disease (NMOSD) (n = 3, 11%), and acute disseminated encephalomyelitis (n = 2, 7%). Two participants (7%; 95% confidence interval [CI], 1-24) had subsequent recurrent ON (plus 1 participant who did not complete the 2-year visit); all had MS. Two other participants (7%) had a new episode in their unaffected eye. Mean presenting HCVA was 0.81 logarithm of the minimum angle of resolution (logMAR) (∼20/125), improving to 0.14 logMAR (∼20/25-2) at 6 months, 0.12 logMAR (∼20/25-2) at 1 year, and 0.11 logMAR (20/25-1) at 2 years (95% CI, -0.08 to 0.3 [20/20+1-20/40-1]). Twenty-four participants (79%) had age-normal VA at 2 years (95% CI, 60-90); 21 participants (66%) had 20/20 vision or better. The 6 participants without age-normal VA had 2-year diagnoses of NMOSD (n = 2 participants, 3 eyes), MS (n = 2 participants, 2 eyes), and isolated ON (n = 2 participants, 3 eyes). Mean presenting LCVA was 1.45 logMAR (∼20/500-2), improving to 0.78 logMAR (∼20/125+2) at 6 months, 0.69 logMAR (∼20/100+1) at 1 year, and 0.68 logMAR (∼20/100+2) at 2 years (95% CI, 0.48-0.88 [20/50+1-20/150-1]). CONCLUSIONS: Despite poor VA at presentation, most children had marked improvement in VA by 6 months that was maintained over 2 years. Associated neurologic autoimmune diagnoses were common. Additional episodes of ON occurred in 5 (18%) of the participants (3 relapses and 2 new episodes).

Neovascularization of the optic disc and peripheral retinal ischemia in a child with a novel variant in ALMS1 (Alström syndrome).

Purpose: The ophthalmologic findings in Alström syndrome include cone-rod dystrophy, optic atrophy, optic disc drusen, and retinal telangiectasias with exudative retinopathy. Here we describe peripheral retinal non-perfusion with neovascularization of the disc (NVD) in a child with Alström syndrome-related cone-rod dystrophy. Observations: A six-year-old girl with a diagnosis of Alström syndrome based on a homozygous nonsense likely pathogenic variant in ALMS1 (NM_015120.4:c.4746C > G; p.Tyr1582Ter) was seen in the ophthalmology clinic for nystagmus, photophobia, and poor vision with non-recordable scotopic and photopic electroretinography (ERG) responses. On routine follow-up exam, she was found to have optic disc hyperermia and apparent swelling. Brain and orbital magnetic resonance imaging (MRI) and lumbar puncture with opening pressure measurement were unremarkable. Because the optic disc findings were persistent, she underwent examination under anesthesia with fluorescein angiography, which revealed bilateral neovascularization of the optic disc (NVD) with peripheral retinal non-perfusion. Systemic workup including hemoglobin A1C measurement was normal. She underwent four sessions of bilateral panretinal photocoagulation and three intravitreal injections of anti-vascular endothelial growth factor (VEGF) with subsequent improvement of the NVD in both eyes. Conclusions and importance: Neovascularization of the optic disc may arise in Alström syndrome as a sequela of peripheral retinal ischemia. This finding may be partially responsive to panretinal photocoagulation and intravitreal anti-VEGF therapy.

Characteristics and Outcomes of Idiopathic and Non-idiopathic Ocular Motor Apraxia in Children.

PURPOSE: To systematically compare idiopathic and non-idiopathic ocular motor apraxia (OMA) in children. METHODS: A retrospective chart review was conducted of all children (< 18 years) diagnosed as having OMA from 2010 to 2020. Demographics, clinical characteristics, and oculomotor outcomes were compared for children with idiopathic and non-idiopathic OMA. RESULTS: Thirty-seven children were included, 17 (46%) with idiopathic OMA and 20 (54%) with non-idiopathic OMA. Among patients with non-idiopathic OMA, Joubert syndrome was the most frequent underlying diagnosis (30%). Strabismus (45% vs 12%, P = .04), nystagmus (30% vs 0%, P = .02), and vertical saccade involvement (25% vs 0%, P = .049) were significantly more common in non-idiopathic than idiopathic OMA, respectively. Neuroimaging abnormalities (90% vs 18%, P < .0001) and developmental delays (100% vs 59%, P = .002) were also more frequent in non-idiopathic than idiopathic OMA, respectively. Endocrine disorders (most commonly growth hormone deficiency) were diagnosed in 12% and 20% of children with idiopathic and non-idiopathic OMA, respectively (P = .67). On survival curve analysis, improvement in OMA occurred faster and more frequently in children with idiopathic than non-idiopathic OMA (median time to improvement 56 vs 139 months, respectively, P = .034). CONCLUSIONS: Non-idiopathic OMA is associated with a higher rate of vertical saccade involvement, nystagmus, and developmental delays. These findings should prompt neuroimaging in children with OMA. Additionally, endocrine disorders may be more frequent in children with OMA than the general pediatric population. [J Pediatr Ophthalmol Strabismus. 2022;59(5):326-331.].

Etiology and Outcomes of Acquired Pediatric Sixth Nerve Palsies.

BACKGROUND: Acquired sixth nerve (CN6) palsies in children may be benign or associated with an underlying neurologic condition. In children who presented with isolated (no associated neurologic or ophthalmic symptoms or signs) CN6 palsies, the rate of newly diagnosed neurologic disorders (such as tumors) is unclear. Moreover, the factors associated with spontaneous resolution and amblyopia in children with acquired CN6 palsies are unknown. METHODS: We retrospectively reviewed the charts of all children younger than 18 years diagnosed with CN6 palsy at our institution from 2010 to 2020. We recorded ophthalmologic and neurologic history and examination findings, neuroimaging results, etiology of CN6 palsy, and outcomes including spontaneous resolution and amblyopia. We assessed etiologies of isolated and nonisolated CN6 palsies as well as frequency and factors associated with spontaneous resolution and amblyopia (in children ≤7 years). RESULTS: One hundred seventy-two children met inclusion criteria. Twenty CN6 palsies (12%) were isolated at presentation. Most isolated cases were presumed postviral or postvaccination (50%) or idiopathic (30%), but 2 cases (10%) were associated with newly diagnosed tumors. Spontaneous resolution occurred in 59% of CN6 palsies at a median of 12.3 weeks and was associated with older age (P = 0.03) and nontumor etiology (P = 0.006). Amblyopia developed in 18% of children at risk, exclusively in those with anisometropia, pre-existing strabismus, or younger than 12 months. CONCLUSIONS: Our findings and chart reviews suggest that approximately 10% of isolated acquired pediatric CN6 palsies are associated with a newly diagnosed brain tumor. This risk must be discussed with parents when considering immediate vs delayed neuroimaging. In addition, infants and children ≤7 years with secondary amblyogenic risk factors (anisometropia or pre-existing strabismus) require close follow-up to monitor and treat amblyopia.

Increase in Pediatric Pseudotumor Cerebri Syndrome Emergency Department Visits, Inpatient Admissions, and Surgeries During the COVID-19 Pandemic.

BACKGROUND: Pediatric pseudotumor cerebri syndrome (PTCS) is a vision-threatening condition that is associated with female sex and obesity in pubertal and postpubertal children. It is unknown whether the increase in childhood obesity during the COVID-19 pandemic has affected the rates and characteristics of pediatric PTCS. METHODS: We conducted a retrospective study of children evaluated for PTCS (inpatient or emergency department) at our children's hospital before (March 19, 2015 to March 19, 2020) and during (March 20, 2020 to February 20, 2021) the pandemic. We compared the monthly number of inpatient and emergency department encounters for pediatric PTCS before and during the pandemic. In addition, anthropometric and ophthalmologic characteristics of children evaluated for pediatric PTCS before and during the pandemic were compared. RESULTS: A total of 36 encounters in the 5 years before the pandemic and 26 encounters in the 11 months during the pandemic were identified. The median monthly number of encounters for pediatric PTCS was significantly higher during the pandemic compared with the 5 years before the pandemic (2 vs 0, P = 0.0021). Compared with prepandemic patients, children evaluated during the pandemic were older (median age 16 vs 14 years, P = 0.02), with higher rates of obesity (85% vs 66%, P = 0.05) and lower likelihood of reporting Caucasian race (4% vs 31%, P = 0.02). Pandemic patients had worse presenting visual acuity (median logMAR 0.14 vs 0.05, P = 0.05) and were more likely to have fulminant presentation (23% vs 6%, P = 0.04) and require surgical intervention (23% vs 6%, P = 0.04). CONCLUSIONS: At our children's hospital, the rate of inpatient admissions and emergency department visits for pediatric PTCS increased during the pandemic. The severity of disease and frequency of surgical treatment also increased. Racial and ethnic minorities seem to be disproportionately affected. These changes may be related to increasing rates of childhood obesity during the pandemic.

Validity and reliability of eye tracking for visual acuity assessment in children with cortical visual impairment.

BACKGROUND: Cortical visual impairment (CVI) is the leading cause of pediatric visual impairment in developed countries, but there is currently no evidence-based treatment. A method of visual assessment that captures multiple domains of visual functioning may facilitate evaluation of proposed therapies. We have developed an eye-tracking protocol that evaluates afferent, efferent, and higher-order visual parameters in children with CVI. We report its validity and reliability in assessing visual acuity. METHODS: We recruited 16 children with CVI between the ages of 12 months and 12 years. Visual acuity was assessed clinically using a previously published six-level scale of visual behavior. Grating acuity was assessed by eye tracking using forced-choice preferential looking, which was performed at baseline and 1 month for reliability testing. Validity was assessed by correlating clinical acuity with grating acuity by eye tracking. RESULTS: Clinical visual acuity ranged from 3 to 6 on the six-level scale, and grating acuity ranged from 0.25 to 20 cycles per degree (logMAR 0.18-2.08). There was strong correlation between grating acuity by eye tracking and clinical acuity assessment (ρ = -0.82; P = 0.0002). Test-retest reliability was excellent, with an intraclass correlation coefficient of 0.96 (95% CI, 0.88-0.99). CONCLUSIONS: Eye tracking demonstrates excellent reliability for visual acuity assessment and high correlation with clinical assessment of visual acuity in pediatric CVI. Future research is necessary to determine whether eye tracking can assess other visual and oculomotor parameters in children with CVI, a prerequisite for incorporating this technique into future clinical trials and patient care.

Ophthalmologic characteristics and outcomes of children with cortical visual impairment and cerebral palsy.

BACKGROUND: Cortical visual impairment (CVI) is the most common cause of pediatric visual impairment in developed countries, and cerebral palsy (CP) is diagnosed in approximately half of children with CVI. It is unknown whether children with CVI who also have CP (CVI+CP) have different characteristics and outcomes (with regard to visual acuity, strabismus, and response to strabismus surgery) than children with CVI without CP (CVI-CP). METHODS: The medical records of all children with CVI, with and without CP, evaluated at our institution between 2013 and 2019 were retrospectively reviewed. Presentation and outcomes of children with CVI+CP were compared to those with CVI-CP. RESULTS: A total of 151 children with CVI+CP and 153 children with CVI-CP were included. Children with CVI+CP were more likely to be diagnosed with significant refractive error (53.6% vs 41.2%; P = 0.03), optic atrophy (46.4% vs 32.7%; P = 0.01), and strabismus (82.8% vs 72.5%; P = 0.03) at presentation. Good ocular alignment after strabismus surgery was achieved in 30% of children with CVI+CP and 63.6% of children with CVI-CP (P = 0.48). Of 9 children with long-term (≥8 years) postoperative follow-up, 100% of CVI-CP patients achieved good outcomes compared with 0% of CVI+CP patients (P = 0.0079). Visual acuity at presentation and the percentage of patients who experienced improvement in visual acuity did not differ between groups. CONCLUSIONS: In our study cohort, children with CVI+CP had a higher likelihood of ophthalmic comorbidities and may have worse long-term strabismus surgery outcomes than children with CVI-CP.

Repeated measurements of ERGs and VEPs using chloral hydrate sedation and propofol anesthesia in young children.

PURPOSE: Sedation with chloral hydrate or anesthesia using propofol allow ocular examination and testing in young children, but these drugs may affect electrophysiologic recordings. We compared the flash and pattern ERGs and VEPs recorded with each drug in a cohort of young children enrolled in a prospective study of optic nerve hypoplasia (ONH) syndrome. METHODS: ERGs and VEPs to light-adapted, standard, full-field flashes, to standard and steady-state pattern-reversal (PR) were recorded with cycloplegia in 9 participants. Age range at the first session, with chloral hydrate was 8-23 mo; at the second session with propofol it was 20-29 mo. Examiners masked to the drug and clinical conditions measured the waveforms for longitudinal, paired comparisons between the sessions. RESULTS: Flash ERG amplitudes did not differ between sessions; peak times were longer at the second session (propofol) by clinically insignificant amounts (< 2 ms, p = 0.002). Standard PERGs had larger amplitudes and later peaks in the second session (propofol) than with chloral hydrate (P50 2.9 vs 4.7 µV, p = 0.016 and 43 vs 52 ms, p < 0.001; N95 4.0 vs 6.1 µV, p = 0.003 and 91 vs 98.5 ms p = 0.034.). These differences were present for those with an interval of  > 10 mo between sessions (n = 5, 10 eyes) but not for those with a shorter inter-test interval (< 8 mo, p > 0.05, n = 4). Magnitudes of the steady-state PERGs did not differ between tests but the waveforms had earlier peaks at the second test with propofol. Flash VEP waveforms were present in 10/18 eyes and showed 72% agreement for recordability between sessions. Standard pattern VEPs were recordable in only a few eyes in this cohort with ONH. CONCLUSIONS: Light-adapted flash ERG waveforms were generally similar with chloral hydrate and with propofol. Larger PERGs with later peaks, found in the second session (propofol) could reflect maturation of the PERG generators, as the differences found were associated with a greater age difference between the sessions, but we do not rule out that small differences in the waveforms may be drug-related. There are insufficient VEP data from these children with ONH to identify drug-related or maturational effects on VEPs.

Methods of visual assessment in children with cortical visual impairment.

PURPOSE OF REVIEW: Cortical visual impairment (CVI) is the leading cause of pediatric visual impairment in developed countries. Currently, there is no standardized method of visual assessment in these children, who usually cannot participate in tests designed for typically developing children. A reproducible method of visual assessment that accurately reflects the multitude of visual deficits in CVI is critical to evaluate proposed therapies for this disorder. This review analyzes current research on methods of visual assessment in children with CVI. RECENT FINDINGS: Earlier studies focused on measuring visual acuity in children with CVI. More recent studies have emphasized other aspects of visual function, such as contrast sensitivity, motion detection, and visual search. Current research topics include questionnaires, functional vision assessment (CVI Range), neuropsychological tests of visual perception, and eye tracking. Eye tracking shows promise for visual assessment in both clinical and research settings because it is objective and quantitative, with the ability to assess diverse visual parameters. SUMMARY: Current research on visual assessment in children with CVI focuses on measuring deficits of visual function beyond visual acuity. This research represents an important step toward designing clinical trials to identify effective therapeutics for this increasingly prevalent disorder with heterogeneous manifestations.