Peripheral retinal finding on fluorescein angiography in neuronal ceroid lipofuscinosis type 2 (CLN2).

Classically, peripheral vascular changes in the retina in patients with neuronal ceroid lipofuscinosis type 2 (CLN2) are described as vascular attenuation seen in the late stages of disease on the Weill Connell Ophthalmic Severity Score (WCOSS) staging system. We describe isolated, mild, peripheral vasculitis with peripheral arteriolar dropout identified by fluorescein angiography in patients with a WCOSS grade of stage 2. We believe this vasculitis represents an early vasodegenerative phase of disease that leads to the vascular attenuation seen in later stages of the disease.

Yearly Occurrence and Seasonality of Neuro-ophthalmic Manifestations of Pediatric Lyme Disease.

PURPOSE: To review the neuro-ophthalmic manifestations of Lyme disease at a central Ohio pediatric tertiary care center. METHODS: A retrospective chart review of patients diagnosed as having Lyme disease from September 2015 to September 2020 was completed. Demographic information, diagnosis dates, and manifestations of Lyme disease were recorded. Patients were excluded for age older than 18 years or lack of corroborated Lyme disease diagnosis. Descriptive statistics were performed. RESULTS: Of the 212 cases of pediatric Lyme disease reviewed, 50 patients had neuroborreliosis. The data showed an increase in Lyme disease and neuroborreliosis cases from 2018 to 2020, with a preponderance of diagnoses in the summer months. Twenty-four patients had meningitis, and 6 of these patients (25%) were diagnosed as having bilateral optic disc edema that was clinically consistent with intracranial hypertension. CONCLUSIONS: Papilledema in the setting of Lyme meningitis may be more common than previously reported in central Ohio. If Lyme disease meningitis is suspected, an opening pressure should be recorded at the time of lumbar puncture and, if elevated, an ophthalmologic evaluation for optic nerve edema is indicated. [J Pediatr Ophthalmol Strabismus. 20XX;X(X):XXX-XXX.].

Secondary Intracranial Hypertension in Pediatric Lyme Meningitis.

Lyme disease is the most common vector-borne disease in the United States and has been associated with secondary intracranial hypertension. We reviewed 11 pediatric patients with Lyme-associated secondary intracranial hypertension. All patients presented with headache, ten had papilledema, 7 with a rash, and 5 with a cranial nerve palsy. All patients were treated with acetazolamide, and 3 received combination therapy with furosemide. Three patients were considered to have fulminant intracranial hypertension because of the severity in their presenting courses. Two of the fulminant intracranial hypertension patients were treated with a temporary lumbar drain in addition to medications, whereas 1 fulminant intracranial hypertension patient was treated exclusively with medical therapy alone. The addition of a lumbar drain decreased the time to resolution of papilledema compared to medical management alone. Final visual acuity was 20/20 in each eye of all patients, suggesting that a titrated approach to therapy depending on the severity of presentation can result in good visual outcomes in these cases. Additionally, symptoms can recur after medication wean, so patients should be monitored closely with any discontinuation of intracranial pressure lowering medications.

Low-Dose 0.01% Atropine Eye Drops vs Placebo for Myopia Control: A Randomized Clinical Trial.

Importance: Controlling myopia progression is of interest worldwide. Low-dose atropine eye drops have slowed progression in children in East Asia. Objective: To compare atropine, 0.01%, eye drops with placebo for slowing myopia progression in US children. Design, Setting, and Participants: This was a randomized placebo-controlled, double-masked, clinical trial conducted from June 2018 to September 2022. Children aged 5 to 12 years were recruited from 12 community- and institution-based practices in the US. Participating children had low to moderate bilateral myopia (-1.00 diopters [D] to -6.00 D spherical equivalent refractive error [SER]). Intervention: Eligible children were randomly assigned 2:1 to 1 eye drop of atropine, 0.01%, nightly or 1 drop of placebo. Treatment was for 24 months followed by 6 months of observation. Main Outcome and Measures: Automated cycloplegic refraction was performed by masked examiners. The primary outcome was change in SER (mean of both eyes) from baseline to 24 months (receiving treatment); other outcomes included change in SER from baseline to 30 months (not receiving treatment) and change in axial length at both time points. Differences were calculated as atropine minus placebo. Results: A total of 187 children (mean [SD] age, 10.1 [1.8] years; age range, 5.1-12.9 years; 101 female [54%]; 34 Black [18%], 20 East Asian [11%], 30 Hispanic or Latino [16%], 11 multiracial [6%], 6 West/South Asian [3%], 86 White [46%]) were included in the study. A total of 125 children (67%) received atropine, 0.01%, and 62 children (33%) received placebo. Follow-up was completed at 24 months by 119 of 125 children (95%) in the atropine group and 58 of 62 children (94%) in the placebo group. At 30 months, follow-up was completed by 118 of 125 children (94%) in the atropine group and 57 of 62 children (92%) in the placebo group. At the 24-month primary outcome visit, the adjusted mean (95% CI) change in SER from baseline was -0.82 (-0.96 to -0.68) D and -0.80 (-0.98 to -0.62) D in the atropine and placebo groups, respectively (adjusted difference = -0.02 D; 95% CI, -0.19 to +0.15 D; P = .83). At 30 months (6 months not receiving treatment), the adjusted difference in mean SER change from baseline was -0.04 D (95% CI, -0.25 to +0.17 D). Adjusted mean (95% CI) changes in axial length from baseline to 24 months were 0.44 (0.39-0.50) mm and 0.45 (0.37-0.52) mm in the atropine and placebo groups, respectively (adjusted difference = -0.002 mm; 95% CI, -0.106 to 0.102 mm). Adjusted difference in mean axial elongation from baseline to 30 months was +0.009 mm (95% CI, -0.115 to 0.134 mm). Conclusions and Relevance: In this randomized clinical trial of school-aged children in the US with low to moderate myopia, atropine, 0.01%, eye drops administered nightly when compared with placebo did not slow myopia progression or axial elongation. These results do not support use of atropine, 0.01%, eye drops to slow myopia progression or axial elongation in US children. Trial Registration: ClinicalTrials.gov Identifier: NCT03334253.

Prevalence of cerebrotendinous xanthomatosis among patients diagnosed with early-onset idiopathic bilateral cataracts: final analysis.

Cerebrotendinous xanthomatosis (CTX) is a rare, autosomal recessive bile acid synthesis disorder caused by pathologic variants in CYP27A1, a gene involved in bile acid synthesis. Impaired function in this gene leads to accumulation of plasma cholestanol (PC) in various tissues, often in early childhood, resulting in such clinical signs as infantile diarrhea, early-onset bilateral cataracts, and neurological deterioration. The current study aimed to identify cases of CTX in a population of patients with a greater CTX prevalence than the general population, to facilitate early diagnosis. Patients diagnosed with early-onset, apparently idiopathic, bilateral cataracts between the ages of 2 and 21 years were enrolled. Genetic testing of patients with elevated PC and urinary bile alcohol (UBA) levels was used to confirm CTX diagnosis and determine CTX prevalence. Of 426 patients who completed the study, 26 met genetic testing criteria (PC ≥ 0.4 mg/dL and positive UBA test), and 4 were confirmed to have CTX. Prevalence was found to be 0.9% in enrolled patients, and 15.4% in patients who met the criteria for genetic testing.

Case Series of Rapid Surgical Interventions in Fulminant Intracranial Hypertension.

AIMS: Examine ophthalmologic outcomes and complications of lumbar drain and cerebrospinal fluid shunts in pediatric fulminant intracranial hypertension. METHODS: Patients under 21 years of age with a diagnosis of fulminant intracranial hypertension with temporary lumbar drain only, shunt after lumbar drain, and shunt only were included. Parameters investigated include lumbar drain data, medication freedom, time to resolution of papilledema, improvement in cranial nerve palsy, afferent pupillary defects, visual fields, visual acuity, and complications of each intervention. RESULTS: Four patients had temporary lumbar drain, 2 temporary lumbar drain and cerebrospinal fluid shunt, and 3 shunt only. All achieved medication freedom and resolution of papilledema and cranial nerve palsies (if present). Most had resolution of preprocedure afferent pupillary defects. Minor residual visual field deficits occurred in 67%, and all had visual acuity improvement. One patient's lumbar drain dislodged, and one patient had 2 cerebrospinal fluid shunt revisions. CONCLUSION: Temporary lumbar drain with medical therapy may be a viable first approach to fulminant intracranial hypertension.

Intracranial Hypertension Recurrence Risk After Wean of Intracranial Pressure-Lowering Medication.

BACKGROUND: The proportion of children with recurrent signs and symptoms of intracranial hypertension after medication wean has been reported to be between 18% and 50%. Few studies have reported intracranial hypertension recurrence risk in children while adjusting for each individual's observed follow-up time after medication wean. In addition, the role of intracranial hypertension etiology on the risk of disease recurrence has not been widely studied. METHODS: The medical charts of patients with intracranial hypertension treated with intracranial pressure-lowering medication were analyzed retrospectively for disease recurrence. Baseline characteristics from diagnosis were recorded in addition to information regarding duration of therapy, medication wean, and recurrence. Survival analyses as well as Poisson regression models with time under observation as an offset were performed. RESULTS: One hundred and thirty-three patients were included in the study. The cumulative risk of intracranial hypertension recurrence increased rapidly within the first six months after medication wean and was 1.5% at one month, 9.5% at three months, and 20% at six months. This risk leveled off near 12 to 18 months. CONCLUSIONS: While the cumulative risk of intracranial hypertension recurrence increases most dramatically within the first six months after medication wean, it does not appear to taper until 12 to 18 months. Given the possibility of delayed or asymptomatic recurrences, long-term follow-up is ideal, although patients can likely be seen less frequently after the first 12 to 18 months after medication wean.

Sleep Disturbance in Pediatric Intracranial Hypertension.

STUDY OBJECTIVES: There is a well-established association between headache disorders and sleep disturbances in children, but it is unknown if sleep disturbance plays a role in pediatric intracranial hypertension. The objective of this study was to examine sleep issues related to pediatric intracranial hypertension. METHODS: Patients with intracranial hypertension who were followed in the Pediatric Intracranial Hypertension Clinic were recruited between July 2017 and September 2018. Demographic data was collected from the electronic medical record in addition to patient and parent completed questionnaires. Information on sleep behaviors was gathered using the Children's Sleep Habits Questionnaire, and control data was obtained from patient siblings. Statistical analyses were performed using paired t-tests or two-sample t-tests, as appropriate. RESULTS: Sixty-two pairs of patients and matched sibling controls were compared. There was a statistically significant difference in total sleep disturbance score (control mean 44.3; patient mean 48.1; n=33 pairs, t=-2.2, p=0.035) as well as subscale scores of sleep onset delay (control mean 1.4; patient mean 1.7; n=52 pairs, t=-2.53, p=0.014), parasomnias (control mean 8.5; patient mean 9.5; n=42 pairs, t=-2.59, p=0.013), and sleep disordered breathing (control mean 3.1; patient mean 3.4; n=44 pairs, t=-2.61, p=0.013). There was no difference found in bedtime resistance, sleep duration, sleep anxiety, night wakings, and daytime sleepiness subscales. Furthermore, there was no difference in total sleep disturbance score between patient subsets including: primary versus secondary intracranial hypertension, body mass index, pubertal status, presence of headaches, or intracranial hypertension treatment. CONCLUSIONS: This observational study suggests that pediatric intracranial hypertension is associated with a modest increase in sleep disturbances.

Sleep disturbance in pediatric intracranial hypertension.

STUDY OBJECTIVES: There is a well-established association between headache disorders and sleep disturbances in children, but it is unknown whether sleep disturbance plays a role in pediatric intracranial hypertension. The objective of this study was to examine sleep issues related to pediatric intracranial hypertension. METHODS: Patients with intracranial hypertension in the Pediatric Intracranial Hypertension Clinic were recruited between July 2017 and September 2018. Demographic data were collected from the electronic medical record in addition to patient and parent completed questionnaires. Information on sleep behaviors was gathered using the Children's Sleep Habits Questionnaire, and control data were obtained from patient siblings. Statistical analyses were performed using paired t tests or two-sample t tests, as appropriate. RESULTS: Sixty-two pairs of patients and matched sibling controls were compared. We found a statistically significant difference in total sleep disturbance score (control mean, 44.3; patient mean, 48.1; n = 33 pairs, t = -2.2, P = .035), as well as subscale scores of sleep onset delay (control mean, 1.4; patient mean, 1.7; n = 52 pairs, t = -2.53, P = .014), parasomnias (control mean, 8.5; patient mean, 9.5; n = 42 pairs, t = -2.59, P = .013), and sleep-disordered breathing (control mean, 3.1; patient mean, 3.4; n = 44 pairs, t = -2.61, P = .013). No difference was found in bedtime resistance, sleep duration, sleep anxiety, night awakenings, and daytime sleepiness subscales. Furthermore, no difference was found in total sleep disturbance score between patient subsets, including primary vs secondary intracranial hypertension, body mass index, pubertal status, presence of headaches, or intracranial hypertension treatment. CONCLUSIONS: This observational study suggests that pediatric intracranial hypertension is associated with a modest increase in sleep disturbances.

Equivalence of Oral Fluorescein Angiography to Intravenous Fluorescein Angiography in Evaluating Pediatric Optic Nerve Pathology.

Differentiating true optic nerve edema from pseudo-optic nerve edema is a diagnostic dilemma faced by pediatric ophthalmologists. This case series suggests that oral fluorescein angiography is equivalent to intravenous fluorescein angiography in making this distinction. [J Pediatr Ophthalmol Strabismus. 2019;56:e68-e72.].

Surgical intervention in pediatric intracranial hypertension: incidence, risk factors, and visual outcomes.

PURPOSE: To evaluate the incidence of surgical intervention in pediatric intracranial hypertension (IH), evaluate the visual outcomes of surgically managed patients, and identify potential predictors for surgical intervention. METHODS: The medical records of patients with primary and secondary IH at Nationwide Children's Hospital from 2010 to 2017 were reviewed retrospectively. Presenting characteristics of medically and surgically managed patients were compared, and the clinical courses of surgically managed patients were reviewed. RESULTS: A total of 129 medically and 14 surgically managed patients were included. The surgical incidence was 9.8%. Final visual acuity in 27 of 28 surgically managed eyes was 20/25 or better. In combined primary and secondary IH patients, elevations in body mass index (BMI; OR = 1.06; 95% CI, 1.01-1.11; P = 0.022) and lumbar puncture opening pressures ≥52 cm H2O (OR = 6.17; 95% CI, 1.93-19.67; P = 0.002) were significantly associated with the likelihood of surgical intervention when assessed by univariate logistic regression; grade of papilledema >2 was of marginal significance. After controlling for BMI, a lumbar puncture opening pressure of ≥52 cm H2O was more likely to result in surgery (adjusted OR = 4.69; 95% CI = 1.39-15.98; P = 0.013). CONCLUSIONS: Most pediatric IH can be treated medically. Patients with lumbar puncture opening pressures ≥52 cm H2O at the time of diagnosis are at a higher risk of surgical intervention and should be monitored closely. Elevations in presenting BMI and grade of papilledema may also increase the odds of surgery.

Intracranial hypertension: a current review.

PURPOSE OF REVIEW: To provide a current review of recent publications with regards to intracranial hypertension. RECENT FINDINGS: Attempts were made to provide pediatric data; however, the recent completion of the Idiopathic Intracranial Hypertension Treatment Trial (IIHTT) has provided a wealth of data with regards to adult intracranial hypertension.The pediatric incidence of intracranial hypertension ranges between 0.63 and 0.71 per 100 000 children. A majority of pediatric cases responded to acetazolamide, with resolution of headache averaging 3.8 weeks. Most patients require less than 1 year of treatment with male sex, older age at diagnosis, primary intracranial hypertension, and lack of headache being predictors of good response. Fluorescein angiography has the highest accuracy in distinguishing true papilledema from pseudopapilledema. The IIHTT found Frisen grade of papilledema was within 1 grade in 92.8% of patients. Monitoring of potassium levels is not required and aplastic anemia was not seen in patients taking acetazolamide. SUMMARY: Although the newer pediatric studies report incidence rates in pediatric intracranial hypertension are lower than seen in adults, intracranial hypertension is still a concern in pediatrics. There has been a wealth of information with regards to symptomatology, treatment, and outcomes from the IIHTT that will hopefully assist with management in the pediatric population.

A Dosing Study of Bevacizumab for Retinopathy of Prematurity: Late Recurrences and Additional Treatments.

PURPOSE: Intravitreal bevacizumab is increasingly used to treat severe retinopathy of prematurity (ROP), but it enters the bloodstream, and there is concern that it may alter development of other organs. Previously we reported short-term outcomes of 61 infants enrolled in a dose de-escalation study, and we report the late recurrences and additional treatments. DESIGN: Masked, multicenter, dose de-escalation study. PARTICIPANTS: A total of 61 premature infants with type 1 ROP. METHODS: If type 1 ROP was bilateral at enrollment, then the study eye was randomly selected. In the study eye, bevacizumab intravitreal injections were given at de-escalating doses of 0.25 mg, 0.125 mg, 0.063 mg, or 0.031 mg; if needed, fellow eyes received 1 dose level higher: 0.625 mg, 0.25 mg, 0.125 mg, or 0.063 mg, respectively. After 4 weeks, additional treatment was at the discretion of the investigator. MAIN OUTCOME MEASURES: Early and late ROP recurrences, additional treatments, and structural outcomes after 6 months. RESULTS: Of 61 study eyes, 25 (41%; 95% confidence interval [CI], 29%-54%) received additional treatment: 3 (5%; 95% CI, 1%-14%) for early failure (within 4 weeks), 11 (18%; 95% CI, 9%-30%) for late recurrence of ROP (after 4 weeks), and 11 (18%; 95% CI, 9%-30%) for persistent avascular retina. Re-treatment for early failure or late recurrence occurred in 2 of 11 eyes (18%; 95% CI, 2%-52%) treated with 0.25 mg, 4 of 16 eyes (25%; 95% CI, 7%-52%) treated with 0.125 mg, 8 of 24 eyes (33%; 95% CI, 16%-55%) treated with 0.063 mg, and 0 (0%; 95% CI, 0%-31%) of 10 eyes treated with 0.031 mg. By 6 months corrected age, 56 of 61 study eyes had regression of ROP with normal posterior poles, 1 study eye had developed a Stage 5 retinal detachment, and 4 infants had died of preexisting medical conditions. CONCLUSIONS: Retinal structural outcomes are very good after low-dose bevacizumab treatment for ROP, although many eyes received additional treatment.

Retinopathy of prematurity.

Premature infants born at 30 weeks' gestational age or younger, or 1500 g or smaller, are screened for retinopathy of prematurity (ROP). Guidelines for supplemental oxygen in neonatal intensive care units have decreased but not eliminated the incidence of severe ROP. The underlying cause for ROP is prematurity and low birth weight, and with the survival of smaller and younger babies, ROP continues to be a significant problem facing premature infants. Threshold ROP is treated with retinal photocoagulation, but newer treatments such as intraocular injections of bevacizumab (Avastin) are being used alone or in conjunction with laser.