Introduction
Cerebral visual impairment (CVI) results from damage to cerebral visual processing structures. It is the most common cause of pediatric visual impairment in developed countries and ...rising in prevalence in developing nations. There is currently limited understanding on how neurologic, developmental, and ophthalmic factors predict outcome for pediatric CVI.
Method
A retrospective manual chart review of pediatric CVI patients seen at the tertiary pediatric hospital neurology and neuro-ophthalmology service between 2010 and 2019 was conducted. Patients were stratified into severity groups (based on a custom CVI grading score), and followed over time to identify outcome predictors. Collected baseline characteristics included perinatal, genetic, developmental, and neurologic history, along with neuroimaging and fundoscopic findings on examination. Longitudinal data collected included age, seizure control, and type of therapy received. Linear mixed-effect models were used for longitudinal CVI grade outcome analysis.
Results
A total of 249 individuals spanning 779 patient visits were identified. Mean age at diagnosis was 18.8 ± 16.8 months (2–108 months). About 64.3% were born at term age. Perinatal history revealed hypoxic ischemic encephalopathy (HIE) in 16.5%, intraventricular hemorrhage (IVH) in 11.6%, and seizures in 21.7%. At presentation, 60.3% had a diagnosis of cerebral palsy and 84.7% had developmental delay. Among all subjects, 78.6% had epilepsy; 33.8% had an epileptic encephalopathy, with spasms/hypsarrhythmia being most common. Abnormal neuroimaging was present in 93.8%. Genetic anomalies were present in 26.9%. Baseline visual examination revealed no blink-to-light (BTL) in 24.5%; only BTL in 34.5%, fixation/tracking in 26.5%, and optokinetic drum follow in 14.4%. Longitudinal data analysis showed that perinatal history of HIE, a positive epilepsy history, using multiple (≥3) epilepsy medications, cerebral palsy, and abnormal fundoscopic findings were all negatively associated with CVI grade change over time. After controlling for significant confounders, receiving any type of therapy early childhood intervention (ECI), physical and occupational therapy (PT/OT), refractive error correction or glasses was significantly associated with longitudinal improvement in CVI grade compared to patients who did not receive any therapy, with glasses yielding the largest benefit.
Conclusion
This study offers extensive insights into neurologic, developmental and ophthalmologic features in patients with moderate to severe CVI. In concordance with previous findings, aspects of perinatal history and epilepsy/seizure control may help inform severity and prognosis in the general neurology or ophthalmology clinic. Conversely, these aspects, as well as genetic and specific epilepsy traits may alert vision health care providers in the clinic to pursue visual evaluation in at-risk individuals. Longitudinal follow-up of CVI patients showed that interventional therapies demonstrated vision function improvement greater than no therapy and maturational development.
Diabetic retinopathy (DR) is a microvascular complication of type 2 diabetes (T2D) and a major cause of vision loss worldwide. The TODAY study reported a DR prevalence of 51% among patients with ...youth onset T2D (average T2D duration 13.3 years, mean age of 26.4 years). Prevalence rates of DR in youth-onset T2D with shorter duration and younger age is unclear.
In a multicenter analysis, eye exams or retinal images from patients with youth-onset T2D at Cincinnati Children’s, Johns Hopkins, and University of Wisconsin were assessed for presence of DR using t-tests and fisher’s exact test.
The study included 228 youth (mean age 16.5±3.5years, mean T2D duration 3.0±2.6 years). Seven participants (3%) were positive for DR. Compared to youth negative for DR (n=221), those with DR (n=7) had a longer duration of diabetes (5.3±3.1 v. 2.9±2.6years, p=0.015) and higher hemoglobin A1c at the time of the diabetic eye exam (10.0±2.1 v. 7.5±2.6%, p=0.012). There were no differences in age, race/ethnicity, sex, or types of medication prescribed between those with and without DR. Of those with DED, when compared to all other ethnicities, NH Black youth had a higher rate of positive diabetic eye exams (p=0.04).
Our study found a lower prevalence of DR in youth with T2D at younger age and shorter duration of diabetes. Further work is needed to determine the inflection point when the incidence of DR increases.
Disclosure
R.Channa: None. R.M.Wolf: Research Support; Dexcom, Inc., Boehringer Ingelheim Inc. A.S.Shah: None. V.S.Shah: None. M.Bahrainian: None. E.A.Brown: None. T.Liu: None. B.Magella: None. H.Lehmann: None. M.D.Abràmoff: Board Member; Digital Diagnostics, Consultant; AbbVie Inc., NovaGo Therapeutics AG, Other Relationship; Digital Diagnostics, Stock/Shareholder; Digital Diagnostics.
Funding
National Eye Institute (R01EY033233, 5K23EY030911-03)
Purpose
The purpose of the study was to present a rare case of pediatric bilateral optic neuropathy and retinopathy, which was consistent with a diagnosis of autoimmune retinopathy. We also reviewed ...the most current literature and phenotypes associated with reported pediatric cases of autoimmune retinopathy.
Design
The design of the study was a case report, with a retrospective case series literature review.
Subjects
This study incorporated data from six subjects, with one presenting as an original case report and five being identified from the English-language literature published to date.
Materials and methods
The materials and methods involved a descriptive analysis of fundus findings, electrophysiologic testing, serum autoantibody testing, optical coherence tomography (OCT), brain MRI scanning, and fluorescein angiography, which were performed where available.
Main outcome measures
The study evaluated the clinical presentation and treatment outcomes of all subjects and followed their visual function over time.
Results
All six subjects had retinal abnormalities that were documented on imaging, while five out of the six subjects had optic nerve abnormalities. Electrophysiologic testing was performed on three subjects, all of whom recorded abnormal results. An underlying neoplastic disorder was described for four subjects. Serum autoantibody testing results were available for four subjects. The serum testing included using antibodies against a 22-kDa antigen, a 35-kDa optic nerve-derived antigen, a 62-kDa antigen, enolase, recoverin, tubulin, and pyruvate kinase M2. Our subject presented 12 years after resection of a ganglioglioma with asymmetric bilateral vision loss, disc edema in one eye, advanced disc pallor in the fellow eye, and bilateral subtle retinal infiltrates, despite having a normal fluorescein angiogram. OCT demonstrated asymmetric ganglion cell layer thinning, which is consistent with the vision loss. Our subject also had abnormal brain MRI findings of widespread pachymeningeal enhancement, but he had a normal cerebrospinal fluid composition. He was initially treated with high-dose pulse steroids, followed by intravenous immunoglobulin therapy. He experienced partial visual recovery in both eyes.
Conclusions
Pediatric autoimmune retinopathy and optic neuropathy are rare diseases that can present with unique signs and symptoms. In pediatric patients who present with symptoms of subacute progressive vision loss with negative inflammatory workups, a history of prior neoplasm, and/or clinical findings of progressive retinopathy or optic neuropathy, an autoimmune process should be considered in the differential.
Optic neuritis (ON) in children is uncommon. There are limited prospective data for visual acuity (VA) outcomes, associated diseases, and neuroimaging findings. Prospective data from a large sample ...would be useful for counseling families on treatment decisions and prognosis.
To prospectively study children with a first episode of ON, describe VA after 6 months, and ascertain the network's (Pediatric Eye Disease Investigator Group and Neuro-Ophthalmology Research Disease Investigator Consortium) ability to enroll pediatric patients with ON prospectively.
This nonrandomized cohort study was conducted from September 20, 2016, to July 20, 2018, at 23 sites in the United States and Canada in pediatric ophthalmology or neuro-ophthalmology clinics. A total of 44 children (aged 3-15 years) presented with a first episode of ON (visual loss, pain on eye movements, or both) within 2 weeks of symptom onset and at least 1 of the following in the affected eye: a distance high-contrast VA (HCVA) deficit of at least 0.2 logMAR below age-based norms, diminished color vision, abnormal visual field, or optic disc swelling. Exclusion criteria included preexisting ocular abnormalities or a previous episode of ON.
Primary outcomes were monocular HCVA and low-contrast VA at 6 months. Secondary outcomes were neuroimaging, associated diagnoses, and antibodies for neuromyelitis optica and myelin oligodendrocyte glycoprotein.
A total of 44 children (mean age SD, 10.2 3.5 years; 26 boys 59%; 23 White individuals 52%; 54 eyes) were enrolled in the study. Sixteen patients (36%) had bilateral ON. Magnetic resonance imaging revealed white matter lesions in 23 children (52%). Of these children, 8 had myelin oligodendrocyte glycoprotein-associated demyelination (18%), 7 had acute disseminated encephalomyelitis (16%), 5 had multiple sclerosis (11%), and 3 had neuromyelitis optica (7%). The baseline mean HCVA was 0.95 logMAR (20/200), which improved by a mean 0.76 logMAR (95% CI, 0.54-0.99; range, -0.70 to 1.80) to 0.12 logMAR (20/25) at 6 months. The baseline mean distance low-contrast VA was 1.49 logMAR (20/640) and improved by a mean 0.72 logMAR (95% CI, 0.54-0.89; range, -0.20 to 1.50) to 0.73 logMAR (20/100) at 6 months. Baseline HCVA was worse in younger participants (aged <10 years) with associated neurologic autoimmune diagnoses, white matter lesions, and in those of non-White race and non-Hispanic ethnicity. The data did not suggest a statistically significant association between baseline factors and improvement in HCVA.
The study network did not reach its targeted enrollment of 100 pediatric patients with ON over 2 years. This indicates that future treatment trials may need to use different inclusion criteria or plan a longer enrollment period to account for the rarity of the disease. Despite poor VA at presentation, most children had marked improvement by 6 months. Associated neurologic autoimmune diagnoses were common. These findings can be used to counsel families about the disease.
BACKGROUND
Sporadic optic pathway/hypothalamic gliomas represent a unique entity within pediatric low‐grade glioma. Despite favorable survival, location makes treatment difficult and local ...progression debilitating. This study is a longitudinal assessment of visual acuity (VA) among children treated within the last 2 decades.
METHODS
Clinical characteristics were ed for patients treated from 2000 to 2018 at Texas Children's Cancer Center in Houston. Ophthalmologic data taken at 3‐ to 6‐month intervals were examined with age‐appropriate VA metrics converted to the LogMAR (logarithm of the minimum angle of resolution) scale. Kaplan‐Meier blindness‐free survival (BFS) curves, calculated as time‐to‐bilateral functional blindness (LogMAR ≥0.8 in both eyes), were calculated for patients receiving early radiation therapy (RT; upfront or as first‐line salvage treatment) or chemotherapy (CT) and evaluated using the log‐rank test.
RESULTS
Thirty‐eight patients with a median follow‐up of 8.5 years (range, 2‐17 years) were identified. Median age at diagnosis was 3 years (interquartile range, <1‐6 years). Early RT was administered in 11 patients (29%). Twenty‐seven patients (71%) were treated primarily with CT, initiated at a median age of 3.5 years (range, <1‐11 years). Eight patients in the CT group did eventually require RT secondary to VA loss and following multiple lines of CT. Median age at RT for all patients was 11 years (range, 3‐17 years). BFS rates were 81% at 5 years and 60% at 8 years for CT and 100% at 5 and 8 years for early RT (P = .017).
CONCLUSIONS
In a contemporary cohort, early RT, defined as initial or first‐line salvage therapy, was found to have superior BFS for appropriately selected patients with sporadic optic pathway/hypothalamic gliomas.
LAY SUMMARY
Children with low‐grade brain tumors of the optic pathway generally have excellent long‐term survival; however, given the location of these tumors, there can commonly be threatened vision if the tumor grows.
Although radiation is generally deferred in children on the basis of legitimate concerns regarding the effects on the developing brain, it may represent a vision‐preserving therapy for well‐selected older patients.
The treatment paradigm for pediatric optic pathway glioma has mostly shifted from using radiation therapy (RT) as the definitive therapy to favor postponement of RT for secondary and tertiary lines of systemic therapy. Despite excellent patient survival rates, long‐term vision outcomes with chemotherapy are poor. Well‐selected older patients who receive early RT as upfront or first‐line salvage therapy retain meaningful long‐term visual acuity.
In autoimmune myasthenia gravis (MG), autoantibodies target the neuromuscular junction. Ocular myasthenia gravis (OMG) is localized, affecting only extraocular and/or levator palpebrae muscles. OMG ...presents across all ages, varying in presentation, treatment modalities, and outcomes. Recently, there have been advances in MG/OMG treatment; their utilization and effectiveness are an important part of optimal disease management.
We completed a retrospective chart review of children aged 18 years or younger with a confirmed diagnosis of OMG presenting from 2002 to 2019.
Forty-two patients were included with mean age at presentation of 8.5 years (2 to 18 years). Twenty-one patients (50%) had positive antibodies; 90% had acetylcholine receptor antibodies. Ten patients developed generalized symptoms with mean time to generalization of 13.6 months. Multiple logistic regression showed that older age of onset was a trend predictive factor (P = 0.054; odds ratio 1.17) for generalized disease. All patients were treated with pyridostigmine. Immunomodulating agents included steroids (15), mycophenolate mofetil (four), and intravenous immunoglobulin (one). Three patients underwent thymectomy. Twenty patients reached minimal manifestation status, and 12 achieved remission. Gender, race, and positive antibody status were not statistically significant predictors for advanced immunosuppressive therapy.
We summarize one of the largest cohorts of pediatric patients with OMG who have undergone up-to-date diagnostic and therapeutic regimens. The predictors of outcome and treatment pathway for OMG patients suggested by this report may be further elucidated by future prospective studies.
A 9-year-old girl presented with morning headaches associated with vomiting, gait ataxia, and facial and ocular motor nerve palsies. Her initial imaging was concerning for demyelinating disease. ...After extensive infectious and rheumatologic workup returned negative, she was treated twice with intravenous immunoglobulin and intravenous steroids with near-complete resolution each time. She returned, however, with worsening neurologic deficits and imaging revealing focal ischemic infarction in the brainstem as well as new-onset hydrocephalus. A multispecialty workup was initiated without conclusive diagnosis. A novel, noninvasive test for plasma cell-free DNA established a diagnosis of Cladophialophora bantiana that was confirmed and validated by a brain biopsy taken during a clinical decompensation. Treatment was initiated with systemic voriconazole and intraventricular amphotericin B.
Patients with craniosynostosis with subnormal vision due to papilledema and/or exposure-related corneal decompensation are well documented in the literature; however, there is only a single prior ...documented case of vision compromise secondary to anterior segment dysgenesis and glaucoma in this patient population. This report highlights a case of syndromic craniosynostosis with advanced corneal decompensation and anterior segment dysgenesis that was masked and ultimately delayed the diagnosis of congenital glaucoma.
Neuroretinitis (NR) is an inflammatory disorder that presents with painless vision loss due to optic disc edema, peripapillary detachment, and macular lipid exudation. We report the first two ...documented cases of co-infections of pediatric NR due to Bartonella henselae with HSV and Toxocara cati, respectively.
A 10-year-old female with acute right-sided facial droop, right eye pain, and acute visual loss of the right eye is diagnosed with co-infection of Bartonella and HSV retinitis and is successfully treated with acyclovir, rifampin, and doxycycline. A 13-year-old female with progressive visual loss of the left eye is diagnosed with co-infection of Bartonella and ocular toxocariasis and is successfully treated with doxycycline, rifampin, prednisolone, and albendazole.
Early recognition and multi-modal treatment is necessary to prevent delayed diagnosis and treat the underlying NR causes for optimal visual recovery.
Bosch–Boonstra–Schaaf Optic Atrophy Syndrome (BBSOAS) is an autosomal dominant neurodevelopmental disorder caused by loss‐of‐function variants in NR2F1 and characterized by visual impairment, ...developmental delay, and intellectual disability. Here we report 18 new cases, provide additional clinical information for 9 previously reported individuals, and review an additional 27 published cases to present a total of 54 patients. Among these are 22 individuals with point mutations or in‐frame deletions in the DNA‐binding domain (DBD), and 32 individuals with other types of variants including whole‐gene deletions, nonsense and frameshift variants, and point mutations outside the DBD. We corroborate previously described clinical characteristics including developmental delay, intellectual disability, autism spectrum disorder diagnoses/features thereof, cognitive/behavioral anomalies, hypotonia, feeding difficulties, abnormal brain MRI findings, and seizures. We also confirm a vision phenotype that includes optic nerve hypoplasia, optic atrophy, and cortical visual impairment. Additionally, we expand the vision phenotype to include alacrima and manifest latent nystagmus (fusional maldevelopment), and we broaden the behavioral phenotypic spectrum to include a love of music, an unusually good long‐term memory, sleep difficulties, a high pain tolerance, and touch sensitivity. Furthermore, we provide additional evidence for genotype–phenotype correlations, specifically supporting a more severe phenotype associated with DBD variants.
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