Outcomes of Strabismus Surgery Following Teprotumumab Therapy.

PURPOSE: To investigate the results of patients undergoing surgical treatment for strabismic diplopia in thyroid eye disease (TED) following teprotumumab. DESIGN: Multicenter, retrospective, case series. METHODS: We report 28 patients who underwent extraocular muscle surgery for strabismic diplopia after treatment with teprotumumab at 7 different academic centers. Elapsed time from last teprotumumab dose to the date of surgery, previous orbital decompression, primary preoperative horizontal and vertical deviation, surgical procedure, and 2-month postoperative results were collected from the patient records. RESULTS: Sixteen (57%) patients were diplopia-free after 1 surgery. Three (11%) chose prism spectacles to correct residual diplopia, 2 (7%) used compensatory head posture to resolve diplopia, and 1 (4%) had intermittent diplopia and was functionally improved (choosing no prisms or further surgery). These were considered treatment successes. Three (11%) patients required reoperation, and all were diplopia-free after their second procedure. CONCLUSIONS: Most patients requiring surgery for strabismic diplopia following teprotumumab achieve good outcomes with success rates comparable to series published before the availability of teprotumumab.

Development of a Deep Learning Model for Retinal Hemorrhage Detection on Head Computed Tomography in Young Children.

Importance: Abusive head trauma (AHT) in children is often missed in medical encounters, and retinal hemorrhage (RH) is considered strong evidence for AHT. Although head computed tomography (CT) is obtained routinely, all but exceptionally large RHs are undetectable on CT images in children. Objective: To examine whether deep learning-based image analysis can detect RH on pediatric head CT. Design, Setting, and Participants: This diagnostic study included 301 patients diagnosed with AHT who underwent head CT and dilated fundoscopic examinations at a quaternary care children's hospital. The study assessed a deep learning model using axial slices from 218 segmented globes with RH and 384 globes without RH between May 1, 2007, and March 31, 2021. Two additional light gradient boosting machine (GBM) models were assessed: one that used demographic characteristics and common brain findings in AHT and another that combined the deep learning model's risk prediction plus the same demographic characteristics and brain findings. Main Outcomes and Measures: Sensitivity (recall), specificity, precision, accuracy, F1 score, and area under the curve (AUC) for each model predicting the presence or absence of RH in globes were assessed. Globe regions that influenced the deep learning model predictions were visualized in saliency maps. The contributions of demographic and standard CT features were assessed by Shapley additive explanation. Results: The final study population included 301 patients (187 [62.1%] male; median [range] age, 4.6 [0.1-35.8] months). A total of 120 patients (39.9%) had RH on fundoscopic examinations. The deep learning model performed as follows: sensitivity, 79.6%; specificity, 79.2%; positive predictive value (precision), 68.6%; negative predictive value, 87.1%; accuracy, 79.3%; F1 score, 73.7%; and AUC, 0.83 (95% CI, 0.75-0.91). The AUCs were 0.80 (95% CI, 0.69-0.91) for the general light GBM model and 0.86 (95% CI, 0.79-0.93) for the combined light GBM model. Sensitivities of all models were similar, whereas the specificities of the deep learning and combined light GBM models were higher than those of the light GBM model. Conclusions and Relevance: The findings of this diagnostic study indicate that a deep learning-based image analysis of globes on pediatric head CTs can predict the presence of RH. After prospective external validation, a deep learning model incorporated into CT image analysis software could calibrate clinical suspicion for AHT and provide decision support for which patients urgently need fundoscopic examinations.

UVEAL MELANOMA PRESENTING AS HEPATIC METASTASIS IN A PATIENT WITH OCULODERMAL MELANOCYTOSIS.

PURPOSE: To report an atypical case of occult uveal melanoma in a patient with oculodermal melanocytosis that first presented with symptoms of hepatic metastasis. METHODS: A previously healthy 16-year-old boy with noted ocular hyperpigmentation developed abdominal pain and vomiting and was found to have a hepatic mass consistent with a metastatic lesion from an occult uveal melanoma. RESULTS: On examination, the patient's visual acuity was 20/20, and pupils were reactive without an afferent pupillary defect in both eyes. Examination of the left eye revealed normal findings. In the right eye, conjunctiva was freely moving over hyperpigmented sclera. Dilated fundus examination demonstrated a hyperpigmented, minimally elevated, choroidal mass in the right eye. Results of fundus autofluorescence, IV fluorescein angiography, spectral-domain optical coherence tomography, and ultrasonography were suspicious for uveal melanoma. Genetic testing of the hepatic mass was positive for BAP1, confirming that the metastasis originated as uveal melanoma rather than cutaneous or intracranial melanoma. Magnetic resonance imaging of the brain and orbits showed negative impression for intracranial lesions. A PET scan revealed numerous additional metastatic lesions, and the patient was referred to palliative care. CONCLUSION: Patients with oculodermal melanocytosis are at an increased risk for both uveal melanoma and subsequent metastasis, and frequent monitoring should be performed because treatment options for metastatic uveal melanoma are limited.

Proton therapy and limited surgery for paediatric and adolescent patients with craniopharyngioma (RT2CR): a single-arm, phase 2 study.

BACKGROUND: Compared with photon therapy, proton therapy reduces exposure of normal brain tissue in patients with craniopharyngioma, which might reduce cognitive deficits associated with radiotherapy. Because there are known physical differences between the two methods of radiotherapy, we aimed to estimate progression-free survival and overall survival distributions for paediatric and adolescent patients with craniopharyngioma treated with limited surgery and proton therapy, while monitoring for excessive CNS toxicity. METHODS: In this single-arm, phase 2 study, patients with craniopharyngioma at St Jude Children's Research Hospital (Memphis TN, USA) and University of Florida Health Proton Therapy Institute (Jacksonville, FL, USA) were recruited. Patients were eligible if they were aged 0-21 years at the time of enrolment and had not been treated with previous radiotherapeutic or intracystic therapies. Eligible patients were treated using passively scattered proton beams, 54 Gy (relative biological effect), and a 0·5 cm clinical target volume margin. Surgical treatment was individualised before proton therapy and included no surgery, single procedures with catheter and Ommaya reservoir placement through a burr hole or craniotomy, endoscopic resection, trans-sphenoidal resection, craniotomy, or multiple procedure types. After completing treatment, patients were evaluated clinically and by neuroimaging for tumour progression and evidence of necrosis, vasculopathy, permanent neurological deficits, vision loss, and endocrinopathy. Neurocognitive tests were administered at baseline and once a year for 5 years. Outcomes were compared with a historical cohort treated with surgery and photon therapy. The coprimary endpoints were progression-free survival and overall survival. Progression was defined as an increase in tumour dimensions on successive imaging evaluations more than 2 years after treatment. Survival and safety were also assessed in all patients who received photon therapy and limited surgery. This study is registered with ClinicalTrials.gov, NCT01419067. FINDINGS: Between Aug 22, 2011, and Jan 19, 2016, 94 patients were enrolled and treated with surgery and proton therapy, of whom 49 (52%) were female, 45 (48%) were male, 62 (66%) were White, 16 (17%) were Black, two (2%) were Asian, and 14 (15%) were other races, and median age was 9·39 years (IQR 6·39-13·38) at the time of radiotherapy. As of data cutoff (Feb 2, 2022), median follow-up was 7·52 years (IQR 6·28-8·53) for patients who did not have progression and 7·62 years (IQR 6·48-8·54) for the full cohort of 94 patients. 3-year progression-free survival was 96·8% (95% CI 90·4-99·0; p=0·89), with progression occurring in three of 94 patients. No deaths occurred at 3 years, such that overall survival was 100%. At 5 years, necrosis had occurred in two (2%) of 94 patients, severe vasculopathy in four (4%), and permanent neurological conditions in three (3%); decline in vision from normal to abnormal occurred in four (7%) of 54 patients with normal vision at baseline. The most common grade 3-4 adverse events were headache (six [6%] of 94 patients), seizure (five [5%]), and vascular disorders (six [6%]). No deaths occurred as of data cutoff. INTERPRETATION: Proton therapy did not improve survival outcomes in paediatric and adolescent patients with craniopharyngioma compared with a historical cohort, and severe complication rates were similar. However, cognitive outcomes with proton therapy were improved over photon therapy. Children and adolescents treated for craniopharyngioma using limited surgery and post-operative proton therapy have a high rate of tumour control and low rate of severe complications. The outcomes achieved with this treatment represent a new benchmark to which other regimens can be compared. FUNDING: American Lebanese Syrian Associated Charities, American Cancer Society, the US National Cancer Institute, and Research to Prevent Blindness.

Analgesia in Postoperative Adult Strabismus Patients.

This survey of pediatric ophthalmic surgeons on analgesia for postoperative adult strabismus patients indicates that 65% prescribed acetaminophen and/or nonsteroidal anti-inflammatory drugs (NSAIDs), and 12% to 16% prescribed opioids. Most surgeons reported reasonable control of pain regardless of analgesia. Acetaminophen and/or NSAIDs may adequately control pain, although certain circumstances may warrant opioid prescriptions. [J Pediatr Ophthalmol Strabismus. 2023;60(1):e5-e7.].

Pediatric Craniopharyngioma: The Effect of Visual Deficits and Hormone Deficiencies on Long-Term Cognitive Outcomes After Conformal Photon Radiation Therapy.

PURPOSE: Pediatric patients with craniopharyngioma risk cognitive deficits when treated with radiation therapy. We investigated cognitive outcomes after conformal photon radiation therapy (CRT) and the effect of visual deficits and hormone deficiencies. METHODS AND MATERIALS: One hundred one pediatric patients were enrolled on a single institutional protocol beginning in 1998 (n = 76) or followed a similar nonprotocol treatment plan (n = 25). CRT (54 Gy) was administered using a 1.0- or 0.5-cm clinical target volume margin. Median age at CRT was 9.50 years (range, 3.20-17.63 years). Patients were followed for 10 years with assessment of hearing, vision, hormone deficiencies, and cognitive performance. RESULTS: Intellectual functioning (intelligence quotient) was significantly lower in children treated at a younger age and those who received higher doses to temporal lobes and hippocampi. Black race (-17.77 points, P = .002) and cerebrospinal fluid shunting (-11.52 points, P = .0068) were associated with lower baseline intelligence quotient. Reading scores were lower over time in models incorporating age, shunt, and dose to specific brain structures. Patients treated for growth hormone deficiency within 12 months of CRT had better intelligence and attention outcomes. Among patients with normal baseline vision, the 10-year cumulative incidence of change in visual acuity was 4.00% ± 2.82% and in visual field 10.42% ± 4.48%. Reading scores decreased after treatment (0.7873 points/y, P = .0451) in those with impaired baseline vision. CONCLUSIONS: Cognitive outcomes are selectively affected by dose to brain subvolumes, comorbidities of visual deficits, and treatment of endocrinopathy in pediatric craniopharyngioma. Improved treatment selection, normal tissue sparing methods of irradiation, and posttreatment management of endocrinopathy should be considered.

Ocular Neuromyotonia in Children and Adolescents Following Radiation Treatment of Pediatric Brain Tumors.

PURPOSE: To report five cases of ocular neuromyotonia in children and adolescents following radiation therapy for a variety of pediatric brain tumors. Notably, three cases occurred in children younger than 11 years. METHODS: Case series of five patients with ocular neuromyotonia following proton beam therapy or conventional radiation. RESULTS: Five cases of ocular neuromyotonia were identified following radiation treatment of various pediatric brain tumors. Onset ranged from 5 to 142 months after radiation treatment. The abducens nerve/lateral rectus muscle was affected in three patients, and the trochlear nerve/superior oblique muscle was affected in two patients. Ages at symptom presentation were 4 years (intermittent head tilt), 9 years (intermittent blurry vision and head tilt), 10 years (intermittent blurry vision progressing to intermittent diplopia), 15 years (intermittent diplopia), and 17 years (intermittent diplopia). One patient improved with gabapentin. Two patients experienced spontaneous resolution. One patient died due to meta-static disease, and one patient has planned follow-up. CONCLUSIONS: Ocular neuromyotonia occurs most commonly following radiation to the brain and skull base. Clinicians need to be aware that ocular neuromyotonia presents differently in children (who may not report diplopia) than in adults or adolescents (who typically report diplopia). Two children in this series never reported diplopia, only intermittent head tilt and blurry vision. Ocular neuromyotonia requires a high index of suspicion to diagnose, especially in children. Membrane stabilizers can be used effectively, but observation may be a valid option in children because spontaneous resolution was seen. [J Pediatr Ophthalmol Strabismus. 2022;59(5):338-343.].

Effect of Premature Tube Extrusion for Simple Congenital Nasolacrimal Duct Obstruction: A Comparison of Monocanalicular and Bicanalicular Intubation.

ABSTRACT: The objective of this article is to compare the incidence of premature dislocation of silicone tubes and the effect on treatment success between monocanalicular (MCI) and bicanalicular (BCI) intubation in pediatric patients with simple congenital nasolacrimal duct obstruction. Retrospective comparative case series of 108 eyes of 78 pediatric patients with simple congenital nasolacrimal duct obstruction who underwent probing with either BCI (n = 38 eyes) or MCI (n = 70 eyes) from 2017 to 2020. Premature tube extrusion was defined as any tube removed prior to the 3 month postoperative appointment. Success was defined as resolution of tearing 3 months post tube removal. Ages ranged from 10 months to 5.35 years (mean, 1.95 years; Standard deviation (SD), 0.91). Premature tube extrusion occurred in 15 eyes with BCI and 29 eyes with MCI. Success rates were not significantly different regardless of intubation type between the planned tube removal (90.6%) and the premature tube extrusion cohorts (84.1%), P = 0.89. There was no significant difference in treatment success between the planned tube removal (92.7% MCI, 87% BCI) and the premature tube extrusion cohorts (86.2% MCI, 80% BCI). Complications included 2 infections (1 MCI, 1 BCI) and 2 cases of tube related keratopathy (1 MCI, 1 BCI) that all resolved with tube removal. There were 2 BCI patients that presented to the emergency department for premature tube extrusion. Silicone intubation regardless of stent type is an effective treatment for simple congenital nasolacrimal duct obstruction. There was no significant difference in treatment success between tubes that extrude prematurely, and tubes removed at term based on type of intubation.

Allergic Fungal Sinusitis: Ophthalmic Complications Due to the COVID-19 Pandemic and the Potential of Telemedicine.

We report a case of a 26-year-old female who initially presented to an outside optometrist with complaints of proptosis and decreased visual acuity. Magnetic resonance imaging (MRI) obtained at that time was concerning for allergic fungal sinusitis. Unfortunately, the patient's referral to ophthalmology was delayed due to the coronavirus disease 2019 (COVID-19) pandemic. On presentation to ophthalmology one year later, the patient had clinically deteriorated with significant visual and olfactory loss. She underwent emergent endoscopic sinus surgery by otolaryngology with histological analysis of the sinus debris confirming allergic fungal sinusitis. This is a unique case demonstrating the devastating impact that the COVID-19 pandemic had on patient care for an otherwise treatable condition. We propose the utilization of telemedicine networks as a way to prevent similar complications.

Effect of Age at Primary Intraocular Lens Implantation on Refractive Growth in Young Children.

PURPOSE: To evaluate the effect of age at primary intraocular lens (IOL) implantation on rate of refractive growth (RRG3) during childhood. METHODS: A retrospective chart review was performed for children undergoing primary IOL implantation during cataract surgery. RRG3 was calculated for one eye from each patient using the first postoperative refraction, last refraction that remained stable (< 1.00 diopters [D] change/2 years), and the corresponding ages. RRG3 values for pseudophakic patients operated on from ages 0 to 5 months were compared with values for patients operated on at ages 6 to 23 months and 24 to 72 months. Patients with refractive errors that stabilized were grouped by age at surgery to compare age at refractive plateau. RESULTS: Of 296 eyes identified from 219 patients, 46 eyes met the inclusion criteria. There was a statistically significant difference in RRG3 among age groups. The mean RRG3 value was -19.82 ± 5.23 D for the 0 to 5 months group, -22.32 ± 7.45 D for the 6 to 23 months group (0 to 5 months vs 6 to 23 months, P = .43), and -9.64 ± 11.95 D for the 24 to 72 months group (0 to 5 months vs 24 to 72 months, P = .01). CONCLUSIONS: Age at primary IOL implantation affects the RRG3, especially for children 0 to 23 months old at surgery. Surgeons performing primary IOL implantation in infants may want to use age-adjusted assumptions, because faster refractive growth rates can be expected in young children. [J Pediatr Ophthalmol Strabismus. 2020;57(4):264-270.].

Ocular Complications in School-Age Children and Adolescents after Allogeneic Bone Marrow Transplantation.

PURPOSE: To determine the ocular complications in school-age children and adolescents surviving at least 1 year following allogeneic bone marrow transplantation. DESIGN: Retrospective cohort study. METHODS: In this institutional study, 162 patients (7-18 years old) met our inclusion criteria with a mean age of 13.4 years at bone marrow transplantation. Follow-up ranged from 13 months to 12 years (mean 4 years; median 3.2 years). Patient charts were screened for cataract formation, dry eye, and other anterior and posterior segment diseases. RESULTS: Cataract formation was noted in 57 patients. Univariate analysis showed that fractionated total body irradiation, race, and use of cytarabine significantly increased the incidence of cataract formation (P < 0.05). Multivariate analysis of significant variables showed that total body irradiation was a risk factor for cataract formation. Of the 57 patients (97 eyes) who developed cataracts after bone marrow transplantation, 4 patients (6 eyes) required cataract surgery. After surgery, all patients had visual acuities of 20/20 to 20/25. Of the 162 patients, 51 developed dry eyes. Univariate analysis showed that age at transplantation; steroid use, chronic graft-versus-host disease; use of fludarabine, melphalan, and thiotepa; and receiving no pre-transplantation conditioning regimen prior to bone marrow transplant significantly increased the risk of dry eye syndrome (P < 0.05). In multivariate analysis, chronic graft-versus-host disease was a significant risk factor for dry eye syndrome. CONCLUSIONS: Due to the high incidence of cataract formation and dry eye disease in this population, this study proposes these patients be screened using examinations by a pediatric or general ophthalmologist at least every year.

Long-term visual acuity outcomes after radiation therapy for sporadic optic pathway glioma.

PURPOSE: Children with sporadic optic pathway glioma (OPG) commonly experience a decline in visual acuity (VA). This study aimed to quantify long-term VA outcomes after definitive radiation therapy (RT). METHODS: From 1997 to 2017, 41 patients underwent RT for OPG and had baseline VA testing. All patients underwent serial VA testing every 3-6 months during the first 5 years and annually thereafter. The cumulative incidence of VA decline or improvement (per eye) was estimated using death as a competing risk. RESULTS: Mean follow-up was 5 years. Most tumors (93%) involved the postchiasmatic optic tracts and/or hypothalamus. Of the tumors tested for BRAF alterations (n = 15), 67% had a BRAF fusion. Median time to VA decline was 20 months in the eye with worse vision and 22 months in the better eye. For the worse eye, the 5-year cumulative incidences of VA decline and improvement were 17.9% [95% confidence interval (CI) 7-32.8%] and 13.5% (95% CI 4.7-26.7%), respectively. For the better eye, the 5-year cumulative incidences of VA decline and improvement were 11.5% (95% CI 3.5-30.7%) and 10.6% (95% CI 2.6-25.2%), respectively. Visual outcomes did not correlate with radiographic evidence of tumor progression. CONCLUSIONS: The 5-year cumulative incidence of VA decline was low. VA decline is most likely to occur within the first 2 years after RT and is not associated with radiographic progression of disease, highlighting the need for frequent ophthalmologic exams during this period.

Treatment burden and long-term health deficits of patients with low-grade gliomas or glioneuronal tumors diagnosed during the first year of life.

BACKGROUND: Low-grade gliomas (LGGs) and low-grade glioneuronal tumors (LGGNTs) diagnosed during the first year of life carry unique clinical characteristics and challenges in management. However, data on the treatment burden, outcomes, and morbidities are lacking. METHODS: A retrospective study of LGGs and LGGNTs diagnosed in patients younger than 12 months at St. Jude Children's Research Hospital (1986-2015) was conducted. RESULTS: For the 51 patients (including 31 males), the mean age at diagnosis was 6.47 months (range, 0.17-11.76 months), and the mean follow-up period was 11.8 years (range, 0.21-29.19 years). Tumor locations were hypothalamic/optic pathway (61%), hemispheric (12%), brainstem (12%), cerebellar (8%), and spinal (8%). There were 41 patients with histological diagnoses: 28 had World Health Organization grade 1 tumors, 6 had grade 2 tumors, and 7 had an LGG/LGGNT not definitively graded. Forty-one patients required an active intervention at diagnosis. Throughout their treatment course, 41 patients eventually underwent tumor-directed surgeries (median, 2 surgeries; range, 1-6), 39 received chemotherapy (median, 2 regimens; range, 1-13), and 21 received radiotherapy. Forty patients experienced disease progression (median, 2 progressions; range, 1-18). Ten patients died of progression (n = 5), malignant transformation (n = 2), a second cancer (n = 2), or a shunt infection (n = 1). The 10-year overall survival, progression-free survival, and radiation-free survival rates were 85% ± 5.3%, 16.9% ± 5.3%, and 51.2% ± 7.5%, respectively. Forty-nine patients experienced health deficits (eg, endocrinopathies, obesity, seizures, visual/hearing impairments, neurocognitive impairments, and cerebrovascular disease). Predictors of progression and toxicities were defined. CONCLUSIONS: Infantile LGG/LGGNT is a chronic, progressive disease universally associated with long-term morbidities and requires multidisciplinary intervention.

Neuropsychological outcomes of patients with low-grade glioma diagnosed during the first year of life.

PURPOSE: Low-grade gliomas (LGG) are a heterogeneous group of brain tumors, which are often assumed to have a benign course. Yet, children diagnosed and treated for LGG in infancy are at increased risk for neurodevelopmental disruption. We sought to investigate neuropsychological outcomes of infants diagnosed with LGG. METHODS: Between 1986 and 2013, 51 patients were diagnosed with LGG before 12 months of age and managed at St. Jude Children's Research Hospital. Twenty-five of the 51 patients received a cognitive assessment (68% male; 6.8 ± 3.3 months at diagnosis; 10.5 ± 4.8 years at latest assessment). Approximately half the patients received radiation therapy (n = 12; aged 4.0 ± 3.0 years at radiation therapy), with a median of 2 chemotherapy regimens (range = 0-5) and 1 tumor directed surgery (range = 0-5). RESULTS: The analyses revealed performance below age expectations on measures of IQ, memory, reading, mathematics, and fine motor functioning as well as parent-report of attention, executive, and adaptive functioning. Following correction for multiple comparisons, a greater number of chemotherapy regimens was associated with lower scores on measures of IQ and mathematics. More tumor directed surgeries and presence of visual field loss were associated with poorer dominant hand fine motor control. Radiation therapy exposure was not associated with decline in neuropsychological performance. CONCLUSIONS: Children diagnosed with LGG in infancy experience substantial neuropsychological deficits. Treatment factors, including number of chemotherapy regimens and tumor directed surgeries, may increase risk for neurodevelopmental disruption and need to be considered in treatment planning.

Use of real-time semiquantitative PCR data in management of a neonatal intensive care unit adenovirus outbreak.

OBJECTIVE: To describe an adenovirus outbreak in a neonatal intensive care unit (NICU), including the use of qualitative and semiquantitative real-time polymerase chain reaction (qPCR) data to inform the outbreak response. DESIGN: Mixed prospective and retrospective observational study. SETTING: A level IV NICU in the southeastern United States.PatientsTwo adenovirus cases were identified in a NICU. Screening of all inpatients with qPCR on nasopharyngeal specimens revealed 11 additional cases.InterventionsOutbreak response procedures, including enhanced infection control policies, were instituted. Serial qPCR studies were used to screen for new infections among exposed infants and to monitor viral clearance among cases. Changes to retinopathy of prematurity (ROP) exam procedures were made after an association was noted in those patients. At the end of the outbreak, a retrospective review allowed for comparison of clinical factors between the infected and uninfected groups. RESULTS: There were no new cases among patients after outbreak identification. One adenovirus-infected patient died; the others recovered their clinical baselines. The ROP exams were associated with an increased risk of infection (odds ratio [OR], 84.6; 95% confidence interval [CI], 4.5-1,601). The duration of the outbreak response was 33 days, and the previously described second wave of cases after the end of the outbreak did not occur. Revisions to infection control policies remained in effect following the outbreak. CONCLUSIONS: Retinopathy of prematurity exams are potential mechanisms of adenovirus transmission, and autoclaved or single-use instruments should be used to minimize this risk. Real-time molecular diagnostic and quantification data guided outbreak response procedures, which rapidly contained and fully terminated a NICU adenovirus outbreak.

Isolated Optic Nerve Glioma in Children With and Without Neurofibromatosis: Retrospective Characterization and Analysis of Outcomes.

Isolated optic nerve glioma is a rare tumor with no consensus for the best therapeutic approach. Therefore, tumor control and preservation of visual function remain a challenge. In this retrospective study, we describe our experience over 30 years in a single-institutional cohort of children with isolated optic nerve glioma, focusing on treatments and visual outcomes. Seventeen children were followed for a median period of 8 years (range, 2-22 years). Diagnosis was based on typical neuroradiologic findings, and 3 patients had histologic confirmation of their tumors. In our study, conservative management preserved the vision of most patients with neurofibromatosis type 1 (NF1). NF1-related optic nerve gliomas were less often treated but were associated with a lower probability of progression and with occasional spontaneous regression. Sporadic tumors more frequently exhibited aggressive clinical behavior with a higher propensity for posterior extension, often requiring surgical intervention.

Marked functional recovery and imaging response of refractory optic pathway glioma to BRAFV600E inhibitor therapy: a report of two cases.

BACKGROUND: Despite appropriate therapeutic interventions, progressive optic pathway glioma (OPG) in children may result in loss of vision and other neurologic morbidities. Molecularly targeted therapy against the MAP kinase pathway holds promise in improving outcomes while resulting in lower treatment-related toxicities. We report two children with refractory OPG who had a substantial and early reversal of their neurologic deficits and an impressive imaging response of their tumor to BRAFV600E inhibition therapy. METHODS: Two children with OPG (BRAFV600E-mutated pilocytic astrocytoma) who did not respond to at least one frontline therapy were treated with the oral BRAFV600E inhibitor vemurafenib. RESULTS: Both children had substantial visual compromise before start of therapy, with one child additionally having motor deficits. Both had an early improvement in their vision, and the second child showed a demonstrable improvement in motor weakness. This was accompanied by a decrease in tumor size, which was sustained at 6 months from therapy. Neither child had significant toxicities except for mild skin sensitivity to vemurafenib. CONCLUSIONS: BRAFV600E inhibitor therapy can potentially reverse visual and neurologic decline associated with progressive OPG. The clinico-radiologic response appears to be prompt and marked. Ongoing clinical trials using BRAFV600E inhibitors can help confirm these early promising findings.

Ocular complications in a young pediatric population following bone marrow transplantation.

PURPOSE: To investigate ocular complications associated with bone marrow transplant and associated continued maintenance therapy in a preschool population. METHODS: The medical records of patients <7 years of age were reviewed retrospectively. Patient charts were screened for cataract formation, dry eye, and other anterior and posterior segment disease. RESULTS: Of 270 cases reviewed, 91 met inclusion criteria. Mean age at diagnosis was 3.17 years. Average follow-up was 5.8 years (range, 1.9 months-14.1 years). Of the 91, 37 patients developed cataracts (35 bilaterally) over a 14-year period. Cumulative incidence corrected for competing event (death before cataract) for the study population was found to be 58.4% after 14 years. Univariate analysis for cataract formation showed statistical significance for total body irradiation dose, age at diagnosis, race, donor type (related vs unrelated), product type, diagnosis type, survival status, calcineurin inhibitor use, and bisulfan, cytarabine, and thiotepa use. Multivariate analysis for competing event (death), showed that total body irradiation dose was not statistically significant; however, when studied in a binary logistic regression model, total body irradiation dose was statistically significant. Notably, steroid use and presence of graft-versus-host disease did not show statistical significance for cataract development. No other ocular complication was found in sufficient quantities to allow statistical analyses. CONCLUSIONS: Due to the high incidence of cataract formation in this population, especially those enduring a treatment regimen with total body irradiation, we propose screening examinations by a pediatric or general ophthalmologist at least annually. We also urge a low threshold for treatment of dry eye syndrome.

Children with dorsal midbrain syndrome as a result of pineal tumors.

BACKGROUND: Dorsal midbrain syndrome (also known as Parinaud syndrome and pretectal syndrome) is a well-known complication of tumors of the pineal region. However, there are few reports regarding outcomes, especially in children. The purpose of this study was to report the ophthalmic outcomes in a group of children with pineal tumors treated at a single institution. METHODS: The medical records of pediatric patients diagnosed with pineal region tumors and evaluated at our ophthalmology clinic were studied retrospectively. Descriptive statistics were used to assess rate of dorsal midbrain syndrome, defined as one or more of the following: limitation of upgaze, pupillary light-near dissociation, and convergence retraction nystagmus. Treatment outcomes were recorded. RESULTS: A total of 35 subjects (age range, 5 months to 20 years) were included, 18 (51%) of whom were found to have dorsal midbrain syndrome. Of those 18, 16 patients (89%) had limitation of upgaze, 15 (83%) had pupillary light-near dissociation, and 9 (50%) had convergence-retraction nystagmus. Convergence insufficiency was noted in 5 patients (28%); exotropia (either intermittent or constant), in 9 (50%). Improvement in dorsal midbrain syndrome findings following treatment was seen in 7 of 17 patients (41%), but only 2 (12%) experienced complete resolution. Treatment consisted of surgery, radiation, and/or chemotherapy. CONCLUSIONS: In our study cohort of children with pineal tumors have a high incidence of dorsal midbrain syndrome. Most cases had residual findings after treatment.

Ocular Salvage and Vision Preservation Using a Topotecan-Based Regimen for Advanced Intraocular Retinoblastoma.

Purpose To evaluate topotecan-based therapy for advanced intraocular retinoblastoma. Patients and Methods Twenty-seven patients with bilateral retinoblastoma (male patients, n = 14; median age, 8.4 months) received chemotherapy: two courses of topotecan plus vincristine followed by three alternating administrations of carboplatin and vincristine for two courses and topotecan plus vincristine for one course, with optional periocular carboplatin. Focal therapy was applied after cycle 2. Event-free survival was defined as avoidance of external-beam radiotherapy (EBRT) and enucleation. Results Of 54 eyes, 42 were Reese-Ellsworth group IV to V, and 37 were International Classification of Retinoblastoma group C to E. Eleven eyes were enucleated: one at diagnosis, nine with progressive disease including three eyes treated with EBRT, and one that developed neovascular glaucoma after completion of therapy. One patient was removed from protocol with prolonged infection in course 1; 26 patients (51 eyes) were analyzed. At 10 years, cumulative incidence of EBRT was 5.9% (SE ± 3), and event-free survival was 69.2% (SE ± 27.2). Ocular survival for Reese-Ellsworth group IV to V eyes was 77.5% (SE ± 21.2); it was 74.3% (SE ≥ 18.8) for International Classification group C to E eyes. Vision testing (median age, 7 years; range, 5 to 10 years) documented 20/70 vision or better in one eye of 23 patients; 19 (76%) of 25 patients demonstrated 20/40 vision or better in one eye. All patients experienced thrombocytopenia (41 episodes in 275 courses; 15%). There were 29 episodes of febrile neutropenia (10%). Grade 3 diarrhea was present in nine of 27 patients, and one patient had an allergic reaction to carboplatin. All patients are alive at median follow-up 7.4 years (range, 2.7 to 10 years). Conclusion Topotecan combined with vincristine, carboplatin, and aggressive focal therapies is an effective regimen for the treatment of advanced retinoblastoma and results in globe salvage with vision. Toxicities were anticipated and managed with appropriate supportive care.