Bing-Neel syndrome: a rare neurological complication of Waldenström macroglobulinaemia.

Bing-Neel syndrome (BNS) is a very rare manifestation of Waldenström macroglobulinaemia (WM), in which lymphoplasmacytic cells invade the central nervous system. The clinical presentation includes symptoms of headaches, visual floaters, neuropathy, seizures and gait abnormalities. Here, we describe an elderly woman, who presented with complaints of visual floaters, progressive neuropathy and cognitive changes. Workup including a bone marrow biopsy confirmed the diagnosis of WM. Shortly afterwards, the patient experienced a seizure leading to hospitalisation, which revealed a right frontal lobe lesion on brain MRI. A biopsy of the lesion showed a small B cell lymphoma positive for an MYD88 mutation, confirming BNS. The patient was initially treated with ibrutinib, before transitioning to zanubrutinib. However, she developed disease progression necessitating radiotherapy with lenalidomide and rituximab maintenance therapy, which achieved remission. This case sheds light on the diagnosis and management of a very rare complication of a rare disease.

Qualitative Exploration of the Visual Function Impairments and Health-Related Quality of Life Impacts of Amblyopia in Adult and Pediatric Populations.

INTRODUCTION: Amblyopia is a reduction in vision in one or both eyes due to impaired development of the visual pathway. This study explored the experience of amblyopia and treatment from the patient, caregiver, and clinician perspectives. METHODS: A targeted literature review, including a review of social media listening (SML) studies, was conducted. Next, qualitative interviews were conducted with amblyopia patients, caregivers of children with amblyopia, and ophthalmologists with experience treating patients with amblyopia. The findings informed the development of a disease model. Amblyopia clinical experts provided input at key stages. RESULTS: Twelve data sources were reviewed, including qualitative studies in the literature and SML studies. Overall, 133 patients/caregivers were interviewed (23 adults, 16 adolescents, 47 child-caregiver dyads), plus 10 ophthalmologists from the United States, France, and Germany. Reduced visual acuity, impaired depth perception, impaired peripheral vision, and double vision were the most frequently reported symptoms. Amblyopia impacted daily activities (reading, using digital devices), the ability to move around, school/work (productivity, seeing the board in class), emotional well-being (frustration, sadness), and social functioning (difficulty socializing). Treatments, including patching and corrective lens, also impacted daily activities (using digital devices, sports/leisure), mobility (bumping into things), and work/school (tasks taking longer) as well as emotional well-being (embarrassment), and social functioning (bullying/stigma). CONCLUSION: The findings contribute valuable insights into the adult and pediatric experience of amblyopia from a multi-stakeholder perspective. The findings were used to critically assess existing clinical outcome assessments and supported the development of patient- and observer-reported outcome measures for use in amblyopia clinical trials.

The Amblyopia Quality of Life (AmbQoL): Development and Content Validation of a Novel Health-Related Quality of Life Instrument for Use in Adult and Pediatric Amblyopia Populations.

INTRODUCTION: Amblyopia is a neurodevelopmental vision disorder, characterized by poor vision in one or both eyes. Given the lack of existing clinical outcome assessments (COA) considered fit-for-purpose for amblyopia clinical trials, this study developed new COAs to assess amblyopia symptoms and health-related quality of life (HRQoL) impacts in adult and pediatric amblyopia populations that conform with best practice standards and regulatory guidelines. METHODS: Findings from a targeted qualitative literature review informed the development of three versions of the new Amblyopia Quality of Life Questionnaire (AmbQoL): a patient-reported outcome measure (PRO) for individuals aged 13 years and older, a PRO for children aged 9-12 years, and an observer-reported outcome measure (ObsRO) for caregivers of children aged 4-8 years. Qualitative interviews were conducted with the target populations, and with ophthalmologists experienced in treating amblyopia patients to evaluate the content validity for further development of the AmbQoL. A translatability assessment was conducted to ensure cultural appropriateness and usability across multiple languages. Feedback from Food and Drug Administration (FDA) was also sought on the instruments, and clinical experts provided input at key stages. RESULTS: Interviews were conducted with 112 patients/caregivers and ten ophthalmologists from the USA, France, and Germany. The instructions, items, and response options were well understood across all AmbQoL versions. Feedback from the patients, caregivers, ophthalmologists, the translatability assessment, the FDA, and the expert clinicians informed minor wording modifications to enhance clarity and translatability. Some items were removed due to low relevance. The study resulted in a 23-item adult/adolescent PRO, 24-item child PRO, and 12-item ObsRO, each employing a 7-day recall period. CONCLUSION: Each AmbQoL version has documented support for its face and content validity for use in amblyopia populations aged ≥ 4 years. Further research is necessary to evaluate the psychometric measurement properties of the AmbQoL instruments to enable their use in amblyopia treatment trials.

Pediatric Cerebral Spetzler-Martin Grade 5 Arteriovenous Malformation.

Brain arteriovenous malformations (AVMs) are a type of intracranial high-flow vascular malformation composed of enlarged feeding arteries and draining veins. Without a capillary bed connection, there can be damage to the walls of the arteries and veins, which causes abnormally high blood flow. AVMs are rarely found in children and are thought to expand over time until they become symptomatic. We present an interesting case of a pediatric male who initially presented with seizure-like episodes and was found to have a large frontoparietal Spetzler-Martin (SM) grade 5 AVM after cerebral digital subtraction angiography. Unfortunately, given how much eloquent brain and deep cortical structures were intertwined in the SM5 AVM, risk-benefit analysis favored observation over surgical management. The patient's clinical presentation and imaging findings are described followed by a discussion of the epidemiology, grading system, and treatment of AVMs. After extensive literature review, this clinical entity has been previously reported but is relatively rare in children with prognosis and therapy correlating to the severity of the SM index.

Effect of a Binocular iPad Game vs Part-time Patching in Children Aged 5 to 12 Years With Amblyopia: A Randomized Clinical Trial.

IMPORTANCE: A binocular approach to treating anisometropic and strabismic amblyopia has recently been advocated. Initial studies have yielded promising results, suggesting that a larger randomized clinical trial is warranted. OBJECTIVE: To compare visual acuity (VA) improvement in children with amblyopia treated with a binocular iPad game vs part-time patching. DESIGN, SETTING, AND PARTICIPANTS: A multicenter, noninferiority randomized clinical trial was conducted in community and institutional practices from September 16, 2014, to August 28, 2015. Participants included 385 children aged 5 years to younger than 13 years with amblyopia (20/40 to 20/200, mean 20/63) resulting from strabismus, anisometropia, or both. Participants were randomly assigned to either 16 weeks of a binocular iPad game prescribed for 1 hour a day (190 participants; binocular group) or patching of the fellow eye prescribed for 2 hours a day (195 participants; patching group). Study follow-up visits were scheduled at 4, 8, 12, and 16 weeks. A modified intent-to-treat analysis was performed on participants who completed the 16-week trial. INTERVENTIONS: Binocular iPad game or patching of the fellow eye. MAIN OUTCOMES AND MEASURES: Change in amblyopic-eye VA from baseline to 16 weeks. RESULTS: Of the 385 participants, 187 were female (48.6%); mean (SD) age was 8.5 (1.9) years. At 16 weeks, mean amblyopic-eye VA improved 1.05 lines (2-sided 95% CI, 0.85-1.24 lines) in the binocular group and 1.35 lines (2-sided 95% CI, 1.17-1.54 lines) in the patching group, with an adjusted treatment group difference of 0.31 lines favoring patching (upper limit of the 1-sided 95% CI, 0.53 lines). This upper limit exceeded the prespecified noninferiority limit of 0.5 lines. Only 39 of the 176 participants (22.2%) randomized to the binocular game and with log file data available performed more than 75% of the prescribed treatment (median, 46%; interquartile range, 20%-72%). In younger participants (aged 5 to <7 years) without prior amblyopia treatment, amblyopic-eye VA improved by a mean (SD) of 2.5 (1.5) lines in the binocular group and 2.8 (0.8) lines in the patching group. Adverse effects (including diplopia) were uncommon and of similar frequency between groups. CONCLUSIONS AND RELEVANCE: In children aged 5 to younger than 13 years, amblyopic-eye VA improved with binocular game play and with patching, particularly in younger children (age 5 to <7 years) without prior amblyopia treatment. Although the primary noninferiority analysis was indeterminate, a post hoc analysis suggested that VA improvement with this particular binocular iPad treatment was not as good as with 2 hours of prescribed daily patching. TRIAL REGISTRATION: http://www.clinicaltrials.gov Identifier: NCT02200211.

Intravitreal bevacizumab treatment of bilateral peripapillary choroidal neovascularization from optic nerve head drusen.

Choroidal neovascular membranes are a rare cause of decreased vision in children with optic nerve head drusen. We present a case of bilateral choroidal neovascular membranes associated with optic nerve head drusen in a 5-year-old boy who was successfully treated with a combination of focal laser photocoagulation and intravitreal bevacizumab.

Propranolol for the treatment of orbital infantile hemangiomas.

PURPOSE: To evaluate the treatment of orbital infantile hemangiomas with systemic (oral) propranolol. METHODS: This study was a retrospective observational case series of 5 infants who were diagnosed with orbital infantile hemangiomas between March and July of 2009. RESULTS: The average age at presentation was 3.1 months (3 weeks to 9 months). The patients received oral propranolol, with dosage varying among study centers. The patients were treated for an average of 7.1 months. Treatment of 5 infantile hemangioma patients with oral propranolol produced a significant reduction in the size of the hemangioma in 4 (80%) of the patients and a minimal improvement in one patient. No patient had significant adverse events during the treatment period. CONCLUSION: Oral propranolol may be an effective treatment for orbital infantile hemangiomas.

Duane retraction syndrome type I, Marcus Gunn jaw-winking and crocodile tears in the same eye.

Duane retraction syndrome type I, Marcus Gunn jaw-winking and crocodile tears are all syndromes of congenital aberrant innervation. The authors describe a 17-month-old boy with Duane retraction syndrome type I, Marcus Gunn Jaw-winking, and crocodile tears in the same eye and discuss the proposed mechanisms of these conditions.

Optic nerve findings in CHILD syndrome.

Congenital hemidysplasia with ichthyosiform erythroderma and limb defects (CHILD) syndrome is a rare disorder characterized by birth defects of several organ systems, including the skin, viscera, musculoskeletal system, and central nervous system. The authors present the first report of CHILD syndrome with ocular manifestations in a patient with progressive bilateral optic nerve atrophy.

Multifocal juvenile xanthogranuloma presenting with a hand mass and bilateral vitreous hemorrhage in a neonate.

PURPOSE: To describe a rare case of multifocal juvenile xanthogranuloma (JXG) in a neonate presenting with a large hand mass, bilateral vitreous hemorrhage, and posterior segment involvement. METHODS: Biopsy of hand lesion led to the diagnosis of JXG. Further systemic workup and ocular examination revealed bilateral vitreous hemorrhage and a small, creamy yellowish subretinal lesion above the fovea in the macula of the left eye. In addition, there was a subretinal lesion with overlying vitreous fibrosis in the inferonasal quadrant of the left eye. RESULTS: Treatment with prednisone (2 mg/kg/day) for 2 weeks was initiated before final diagnosis of hand lesion. Steroids were then tapered off over the course of a week with no additional treatment. Follow-up examinations were performed over the course of the next 17 months. On the last follow-up examination at the age of 20 months, the child had central steady and maintained fixation in each eye. The findings of an external ocular examination were unremarkable except for a mild myopic shift in the right eye secondary to trace cataract changes. Dilated fundus examination showed resolution of the lesions in the macula and inferonasal quadrant of the left eye. CONCLUSION: Although rare, JXG should be included in the differential diagnosis of spontaneous vitreous hemorrhage in children under the age of 2 years. Topical, periocular, and oral steroids may improve the ocular signs and symptoms in this condition and should be considered in the management of ophthalmic manifestations of JXG.