An unusual presentation of bilateral optic pathway glioma in Crouzon Syndrome.

Crouzon Syndrome is a genetic craniosynostosis disorder associated with a high risk of ophthalmologic sequelae secondary to structural causes. However, ophthalmologic disorders due to intrinsic nerve aberrations in Crouzon Syndrome have not been described. Optic pathway gliomas (OPGs) are low grade gliomas that are intrinsic to the visual pathway, frequently associated with Neurofibromatosis type 1 (NF-1). OPGs involving both optic nerves without affecting the optic chiasm are rarely seen outside of NF-1. We report an unusual case of bilateral optic nerve glioma without chiasmatic involvement in a 17-month-old male patient with Crouzon Syndrome without any clinical or genetic findings of NF-1. This case suggests that close ophthalmologic follow up and orbital MRIs may benefit patients with Crouzon Syndrome.

Split-Tendon Medial Transposition of Lateral Rectus for Pediatric Complete Oculomotor Palsy.

BACKGROUND: Split-tendon medial transposition of lateral rectus (STMTLR) for complete oculomotor palsy can correct large angles of exotropia in adults, but outcomes are variable, and complications are frequent. Only a few pediatric cases have been reported, and further insight is needed to assess the child's alignment outcomes and ability for postsurgical gain of function. The aim of our study is to report the outcomes of this surgical procedure in pediatric cases of complete oculomotor palsy. METHODS: A retrospective review of outcomes was conducted on 5 consecutive patients with complete oculomotor palsy treated with STMTLR by a single surgeon (V.S.S.) between 2015 and 2021 at tertiary referral centers. Primary outcome was postoperative horizontal alignment, and secondary outcome was demonstration of gain-of-function activity in the field of action of the paretic medial rectus muscle. RESULTS: Five cases of pediatric complete oculomotor palsy underwent surgical treatment with STMTLR. Subjects averaged 5.3 years old (range 10 months-16 years). Two were female. Etiologies were heterogeneous, and all presented with unilateral (n = 2) or bilateral complete oculomotor palsy with exodeviations ranging from 45 to >120 prism diopters. Two subjects had bilateral disease secondary to military tuberculosis with CNS involvement. A third subject presented iatrogenically with complete bilateral third nerve palsies secondary to removal of a nongerminomatous germ cell tumor (NGGCT) of the pineal gland. The 2 remaining subjects had monocular involvement in their right eye, 1 from compressive neuropathy after a cavernoma midbrain hemorrhage, and 1 from a congenital right oculomotor palsy. All patients were observed to have stable ocular alignment for a period of at least 6 months before surgery. Unilateral STMTLR was performed in all cases except the subject with NGGCT, in which bilateral STMTLR was performed. Measurement of alignment permanence out to 1-3 years postop resulted in an average correction of 40.83 prism diopters (range 37.5-45 prism diopters) per operated eye. Four of 5 subjects regained limited but active adduction eye movements, and the 2 unilateral cases demonstrated improved convergence. None of the subjects experienced significant complications. CONCLUSIONS: STMTLR was a safe and effective approach for the surgical correction of complete pediatric oculomotor palsy in our case series. In addition, pediatric patients may benefit from STMTLR with immediate gain-of-function activity in the transposed lateral rectus muscle, which supports the hypothesis that children have a dynamic and adaptive neuroplasticity of visual target selection that predominates established agonist/antagonist neural signaling.

Longitudinal neurological analysis of moderate and severe pediatric cerebral visual impairment.

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.

Pediatric Bartonella henselae neuroretinitis masking co-infections.

PURPOSE: 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. OBSERVATIONS: 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. CONCLUSIONS AND IMPORTANCE: Early recognition and multi-modal treatment is necessary to prevent delayed diagnosis and treat the underlying NR causes for optimal visual recovery.

Early radiotherapy preserves vision in sporadic optic pathway glioma.

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 abstracted 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.

Pediatric Autoimmune Ocular Myasthenia Gravis: Evaluation of Presentation and Treatment Outcomes in a Large Cohort.

BACKGROUND: 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. METHODS: We completed a retrospective chart review of children aged 18 years or younger with a confirmed diagnosis of OMG presenting from 2002 to 2019. RESULTS: 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. CONCLUSIONS: 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.

Double Vision and Gait Ataxia in an Immunocompetent 9-Year-Old Girl With Intracranial Phaeohyphomycosis.

ABSTRACT: 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.

OUTER RETINAL INJURY SECONDARY TO MEMBRANE PEELING WITH INTERNAL LIMITING MEMBRANE FORCEPS.

PURPOSE: To present a case of visually significant retinal injury due to internal limiting membrane (ILM) peeling using ILM forceps alone. METHODS: Case report. RESULTS: A 60-year-old woman who underwent ILM peeling for an epiretinal membrane presented with linear central scotomata. Peeling had been initiated and performed with ILM forceps alone, without the use of other surgical instruments. Fundus examination and spectral domain optical coherence tomography imaging confirmed the presence of several discrete areas of inner and outer retinal injury in the macula, which corresponded to her scotomata. CONCLUSION: This is a case of visually significant retinal injury due to ILM peeling that was performed with ILM forceps alone. Improper peeling technique can transmit injurious forces to the retina. Surgeons must be mindful of the biomechanical forces involved in ILM peeling to minimize traction on the retina.

Assessment of Pediatric Optic Neuritis Visual Acuity Outcomes at 6 Months.

Importance: 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. Objective: 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. Design, Setting, and Participants: 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. Main Outcomes and Measures: 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. Results: 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. Conclusions and Relevance: 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.

Malignant optic nerve glioma in a young woman with 7 year follow up without recurrence.

PURPOSE: To report diagnostic and management challenges of a case of WHO Grade III glioma of the optic nerve occurring in an unusually young patient with more than 7 years of survival without recurrence. OBSERVATIONS: An 18-year-old woman reported rapidly progressive vision loss in the right eye in the setting of a right optic nerve lesion, central retinal artery occlusion, central retinal vein occlusion, and neovascularization of the optic disc. An orbital MRI with contrast demonstrated enhancement of the intraocular, intraorbital, and intracanalicular portion of the right optic nerve. Biopsy of a portion of the intraorbital optic nerve was negative, however, biopsy of the intracranial optic nerve confirmed WHO Grade III glioma (anaplastic astrocytoma). Although the tumor was excised, there remained positive margins at the optic chiasm. The patient was then managed with a combination of radiation and temozolomide. Postoperatively, the initial neovascularization of the optic nerve that had resolved, re-emerged with gliosis. In this setting a concern for intraorbital tumor arose and the globe was enucleated, definitively ruling out neoplasm. The patient has remained tumor free seven years after resection. CONCLUSIONS AND IMPORTANCE: Malignant optic pathway glioma is rare and carries a high 5-year mortality rate. Diagnosis can be elusive given orbital MRI with contrast often appears to be non-specific. Inflammatory changes can be confounding such that a biopsy in the respective area will yield a negative pathologic result. Repeat biopsy is recommended if clinical suspicion is high. Combination treatment of optic nerve tumor resection, temozolomide and radiation has been effective in treating this patient who continues to be followed closely and has had no clinical or radiographic evidence of recurrence in over 7 years. The re-emergence of neovascularization with gliosis/fibrosis of the optic nerve, was driven by ischemia and further precipitated by radiation. To our knowledge this patient represents the youngest reported case of malignant optic nerve glioma with the longest reported survival in the literature to date (over seven years).

Phenotypic expansion of Bosch-Boonstra-Schaaf optic atrophy syndrome and further evidence for genotype-phenotype correlations.

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.

Syndromic Multisuture Craniosynostosis With Associated Anterior Segment Dysgenesis, Optic Nerve Hypoplasia, and Congenital Glaucoma.

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.

Five-Year-Old Boy With Behavioral Changes and Papilledema.

A 5-year-old boy had initial symptoms of behavioral changes, nausea, vomiting, headache, weight loss, and progressive vision failure. Brain MRI revealed abnormal signal intensity in both optic nerves, the optic chiasm, the right medial temporal lobe, and tissues surrounding the right supraclinoid internal carotid artery with associated leptomeningeal and spinal cord enhancement. After nondiagnostic dural and spinal arachnoid biopsies, a temporal lobe biopsy was diagnostic for a rare malignant peripheral nerve sheath tumor.

Systemic Amyloidosis and Extraocular Muscle Deposition.

Isolated amyloid deposition in an extraocular muscle is a rare event but can be a presenting feature of systemic amyloidosis. A 67-year-old woman with an acquired exotropia and hypertropia was found to have unilateral diffuse extraocular muscle enlargement on magnetic resonance imaging. Owing to the progressive nature of her strabismus and the negative laboratory testing for thyroid disease, she underwent an extraocular muscle biopsy that revealed amyloid deposition. Further workup demonstrated a monoclonal gammopathy consistent with systemic amyloidosis. This case demonstrates the need to consider amyloidosis in the differential diagnosis of patients presenting with an atypical acquired strabismus. We review other reports of isolated amyloid deposition in extraocular muscles and its association with systemic amyloidosis, emphasizing the importance of the ophthalmologist in the early recognition of this disease to prevent irreversible, life-threatening end organ damage.