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 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.

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.

Approach for Classification and Severity Grading of Long-term and Late-Onset Health Events among Childhood Cancer Survivors in the St. Jude Lifetime Cohort.

Characterization of toxicity associated with cancer and its treatment is essential to quantify risk, inform optimization of therapeutic approaches for newly diagnosed patients, and guide health surveillance recommendations for long-term survivors. The NCI Common Terminology Criteria for Adverse Events (CTCAE) provides a common rubric for grading severity of adverse outcomes in cancer patients that is widely used in clinical trials. The CTCAE has also been used to assess late cancer treatment-related morbidity but is not fully representative of the spectrum of events experienced by pediatric and aging adult survivors of childhood cancer. Also, CTCAE characterization does not routinely integrate detailed patient-reported and medical outcomes data available from clinically assessed cohorts. To address these deficiencies, we standardized the severity grading of long-term and late-onset health events applicable to childhood cancer survivors across their lifespan by modifying the existing CTCAE v4.03 criteria and aligning grading rubrics from other sources for chronic conditions not included or optimally addressed in the CTCAE v4.03. This article describes the methods of late toxicity assessment used in the St. Jude Lifetime Cohort Study, a clinically assessed cohort in which data from multiple diagnostic modalities and patient-reported outcomes are ascertained. Cancer Epidemiol Biomarkers Prev; 26(5); 666-74. ©2016 AACR.

Residual Strabismus in Children Following Improvement of Cranial Nerve Palsies Affecting Ocular Ductions.

BACKGROUND: Children with brain neoplasms often develop cranial nerve palsies (CNP) affecting ocular ductions. Duction deficits may improve or resolve with treatment of their intracranial disease. However, these children may be left with residual strabismus. METHODS: We identified 104 children with third, fourth, and/or sixth cranial nerve palsies who were treated for central nervous system (CNS) neoplasms. A retrospective chart review was conducted to determine the presence or absence of residual strabismus following resolution of duction deficits. RESULTS: Of the 104 children with CNP secondary to an intracranial neoplasm, forty-five had improvement or resolution of their duction deficit with treatment of their CNS lesion. Of these forty-five children, one had a third cranial nerve palsy, six had fouth cranial nerve palsies (one was bilateral), thirty-seven had sixth cranial nerve palsies (thirteen were bilateral), and one had two different cranial nerve palsies in the same eye (fourth and sixth). Of the eighteen children with improved (but not resolved) duction deficits, only three (17%) experienced resolution of their strabismus. Of the twenty-seven children with resolved duction deficits, nine (33%) experienced resolution of their strabismus. For the children with residual strabismus, the average angle of strabismus before duction deficits improved or resolved was 33.2Δ; while for those children without residual strabismus, it was 20Δ. CONCLUSIONS: Our findings indicated that the majority of children with improved or resolved duction deficits from CNP after treatment for CNS neoplasms are left with residual strabismus. Therefore, we suggest children with CNP secondary to CNS neoplasms need ophthalmic care after duction deficits resolve, as they are likely to have residual strabismus.

Postoperative shift in ocular alignment following single vertical rectus recession on adjustable suture in adults without thyroid eye disease.

PURPOSE: To determine whether overcorrection shifts occur after vertical rectus recession on adjustable suture in the absence of thyroid eye disease. METHODS: The medical records of patients without thyroid eye disease who underwent vertical rectus recession surgery from 2001 to 2008 were retrospectively reviewed for shifts in alignment between suture adjustment at postoperative day 1 and 2 months' follow-up. Superior rectus and inferior rectus recessions were compared. In addition, we compared the use of a nonabsorbable polyester suture to an absorbable polyglactin 910 suture in nonthyroid patients undergoing inferior rectus recessions. RESULTS: A total of 59 patients were included (superior rectus, 30; inferior rectus, 29). We found a mean undercorrection shift of 1.1 (range, 17.5(Δ) undercorrection to 16(Δ) overcorrection) and 1.0(Δ) (range, 12(Δ) undercorrection shift to 6(Δ) overcorrection shift) for superior and inferior rectus recessions, respectively, between 1 day and 2 months postoperatively. CONCLUSIONS: There was no trend toward overcorrection following unilateral vertical rectus adjustable suture recessions in patients without thyroid eye disease, suggesting that thyroid myopathy may account for overcorrection shifts seen with this surgery.

Cognitive function and social attainment in adult survivors of retinoblastoma: a report from the St. Jude Lifetime Cohort Study.

BACKGROUND: Retinoblastoma has a 5-year survival rate exceeding 95%, yet little is known about long-term functional outcomes for these patients. METHODS: Sixty-nine adult survivors of retinoblastoma (mean age, 33 years; mean years post-diagnosis, 31) who had enrolled in the St. Jude Lifetime Cohort Study completed clinical cognitive evaluations and questionnaires assessing adult social attainment. Scores on all cognitive measures were converted to z-scores (M = 0, SD = 1) using age-adjusted normative data. Multivariable linear regression analyses, adjusted for age at diagnosis and disease laterality, were used to examine associations between disease and treatment exposures and cognitive outcomes. RESULTS: Retinoblastoma survivors performed within normative expectations across most cognitive domains. In multivariable models, adjusted for disease laterality, survivors diagnosed at ≤1 year of age performed significantly better on measures of short-term verbal memory (ß = 0.87, P<.01), long-term verbal memory (ß = 0.66, P = .02), verbal learning (ß = 0.67, P = .02), and verbal reasoning abilities (ß = 0.79, P<.01) compared with survivors diagnosed at >1 year of age. In multivariable models, restricted to bilateral survivors and adjusted for age at diagnosis, whole brain radiation exposure was significantly associated with poorer performance on tasks of short-term verbal memory (ß = -0.003, P = .03) and long-term verbal memory (ß = -0.003, P = .01). Reported social attainment was consistent with adult developmental expectations. CONCLUSIONS: Adult survivors of retinoblastoma demonstrate few cognitive or social attainment deficits decades following diagnosis and treatment. Findings suggest the potential for neural reorganization following early insult to the visual system as well as vulnerability of the developing brain to low dose radiation exposure. Early intervention and rehabilitation will be important for these patients.

Persistent binocular diplopia in childhood following successful treatment for esotropia: a case series.

INTRODUCTION: Diplopia is rare in children with nonpathological esotropia because facultative suppression develops prior to visual maturation. Our aim is to present five cases of children with binocular diplopia following treatment of childhood esotropia, exploring possible mechanisms for the development of diplopia based upon the patient's history and findings, and discussing treatment for diplopia in this setting. METHODS: A retrospective chart review of five sequential patients presenting with binocular diplopia following treatment of esotropia was performed. Treatment of esotropia included correction of hyperopic error, correction of anisometropic amblyopia to 20/30 or better, and strabismus surgery as indicated. RESULTS: Diplopia developed in two children with accommodative esotropia, one child with infantile esotropia and partially accommodative esotropia, and two children with a history of infantile esotropia and consecutive exotropia following surgical correction. Diplopia onset occurred between ages 7 and 11. Four of the five children experienced resolution of diplopia with prism glasses. CONCLUSION: Children with esotropia before visual maturation may develop persistent diplopia. Clinical features of the children with diplopia in our case series include poor fusion, poor stereopsis, consecutive exotropia, refractive changes, onset of diplopia after 7 years of age, and occlusion therapy for amblyopia. Prisms may be beneficial in controlling the diplopia.

Cyclosporine 0.05% ophthalmic emulsion for the treatment of radiation-associated dry eye in children.

Dry eye disease is a well-known late complication of radiation therapy and is often difficult to treat. We evaluated the usefulness of cyclosporine 0.05% ophthalmic emulsion for the treatment of radiation-associated dry eye in children. Eleven children received cyclosporine 0.05% emulsion twice daily after failure of conventional therapy. After 6 months, dry eye manifestations improved in three children (27.3%). The remaining eight children showed no improvement with cyclosporine 0.05% ophthalmic emulsion. These results suggest that twice-daily cyclosporine 0.05% ophthalmic emulsion has limited use in children with refractory radiation-associated chronic dry eye.

Pituitary adenoma causing visual disturbances in a 6-year-old girl.

Pituitary adenomas rarely occur in young children, typically present with systemic symptoms, and rarely undergo malignant transformation. We report a 4-year-old girl who presented with visual disturbances initially diagnosed and treated as amblyopia. She subsequently developed headaches and a gait disturbance and was discovered to have a large, suprasellar, nonsecreting pituitary adenoma. The tumor was resected, but 22 months later she developed recurrence with malignant transformation.