Urine catecholamine levels as diagnostic markers for neuroblastoma in a defined population: implications for ophthalmic practice.

PURPOSE: although elevated urinary catecholamine levels have been reported in 90-95% of patients with neuroblastoma, more recent studies of pediatric Horner syndrome caused by an underling neuroblastoma have reported normal values at presentation. The purpose of this population-based study is to report the percentage of cases of neuroblastoma with elevated urinary catecholamine levels at presentation and to suggest a recommended work-up for cases of idiopathic pediatric Horner syndrome. METHODS: the medical records of all pediatric (<19 years) residents of Olmsted County, Minnesota diagnosed with neuroblastoma from 1 January 1969 through 31 December 2008 were retrospectively reviewed. RESULTS: a total of 14 patients <19 years of age were diagnosed with neuroblastoma as residents of Olmsted County, Minnesota, during the 40-year study period. A total of 10 (71%) of the 14 cases manifested elevated urinary catecholamine metabolites at the initial presentation. Urinary vanillylmandelic acid (VMA) levels were greater than twice the upper limit of normal in eight (57%) of 14 cases, whereas homovanillic acid (HVA) levels were greater than two times the upper limit of normal in 10 (71%) of the 14 cases. Three (75%) of the four cases without significantly elevated urinary VMA or HVA levels were diagnosed with stage IV disease, whereas one (25%) had stage II neuroblastoma. CONCLUSION: urinary catecholamine levels were significantly elevated at presentation in 10 (71%) of the 14 neuroblastoma cases during the 40-year study period, suggesting that greater emphasis be placed on performing a thorough physical examination and obtaining warranted imaging studies in cases of idiopathic pediatric Horner syndrome.

Histologic studies of the intraocular toxicity of imatinib mesylate in rabbits.

PURPOSE: To evaluate histologic signs of toxicity of the protein tyrosine kinase inhibitor, imatinib mesylate, in rabbit eyes. METHODS: Twenty Dutch-belted rabbits underwent intravitreal injections of 0.1 ml solutions of imatinib mesylate. Ten rabbits were killed and enucleated 1 week after injection of imatinib mesylate (1.65 mg (four eyes), 165 microg (four eyes), and 16.5 microg (two eyes)). Ten rabbits injected with imatinib mesylate (165 microg (five eyes) and 825 microg (five eyes)) were enucleated 1 month later. Eyes were fixed in 10% formalin and stained with haematoxylin and eosin for microscopic examination. RESULTS: All four eyes injected with 1.65 mg of imatinib mesylate and enucleated at 1 week demonstrated ocular toxicity. All four eyes injected with 165 microg and enucleated at 1 week showed no ocular toxicity. One of the two eyes injected with 16.5 microg and enucleated at 1 week revealed focal areas of subretinal fluid and retinal undulations, suggestive of retinal oedema. None of the 10 eyes injected with imatinib mesylate at either the 165 or 825 microg dose and enucleated at 1 month showed ocular toxicity. CONCLUSIONS: Imatinib mesylate at 1.65 mg caused extensive retinal toxicity in rabbit eyes. In contrast, lower doses did not appear to cause toxicity, but may be associated with retinal oedema.

Intraocular use of rituximab.

PURPOSE: To evaluate the toxicity of 1 mg of intraocular rituximab and to present a small case-series of patients treated with intravitreal rituximab. METHODS: Rituximab (1 mg/0.1 ml) was injected in the vitreous of one eye of three Dutch-belted rabbits. Two animals were injected with balanced salt solution as controls. At 1 month the rabbits were killed and the eyes examined by light microscopy. Three patients (five eyes) with intraocular lymphoma were also treated with a 1 mg injection of rituximab. RESULTS: The treated rabbit eyes and the control eyes showed no light microscopic evidence of ocular toxicity at 1 month following injection. The five human eyes of three patients have shown no evidence of intraocular toxicity with a median follow-up time of 3.6 months (range 2.0-6.4 months). One patient received a total of four injections in the right eye and three injections in the left eye. CONCLUSION: Intravitreal rituximab at a dose of 1 mg does not appear to cause toxicity in rabbit eyes and in the five eyes of three patients.

Common forms of childhood esotropia.

OBJECTIVE: To determine the most common forms of childhood esotropia. DESIGN: Prospective, consecutive, observational case series. PARTICIPANTS: All esotropic children younger than 11 years of age from a predominantly rural Appalachian region evaluated from August 1, 1995 through July 31, 1998. METHODS: Demographic and clinical data were collected for all patients. MAIN OUTCOME MEASURES: The percentage ratio of the various forms of childhood esotropia. RESULTS: Two hundred twenty-one consecutive children without prior surgical treatment were evaluated for esotropia. One hundred seventeen (52.9%) of the 221 children had some form of accommodative esotropia, 38 (17.2%) were associated with congenital or acquired abnormalities of the central nervous system, 23 (10.4%) displayed acquired nonaccommodative esotropia, 15 (6.8%) resulted from ocular sensory defects, 12 (5.4%) had confirmed congenital esotropia, seven (3.2%) had paralytic esotropia, and an unverified age at onset prevented an accurate categorization in the remaining nine (4.1%). CONCLUSIONS: Children with accommodative esotropia accounted for more than half of the study patients and were diagnosed nearly 10 times more frequently than children with congenital esotropia. Esotropic patients with central nervous system defects or with an acquired nonaccommodative deviation were also more common than children with congenital esotropia. Children with congenital esotropia or with a paralytic or sensory cause of their deviation were relatively uncommon.

Acquired nonaccommodative esotropia in childhood.

PURPOSE: Acquired nonaccommodative esotropia (ANAET) in childhood is reported to occur infrequently and is often associated with an underlying neurologic or neoplastic disorder. The primary objective of this study was to ascertain the prevalence and clinical characteristics of this form of childhood esotropia. METHODS: A cohort of all children younger than 11 years with esotropia from a predominantly rural Appalachian region was prospectively identified from August 1, 1995, through July 31, 1998. The age at onset, family history of strabismus, perinatal and medical history, ophthalmologic findings, and surgical results were reviewed for all patients with ANAET. RESULTS: Twenty-three (10.4%) of 221 consecutive children with esotropia were diagnosed with ANAET compared with 12 (5.4%) diagnosed with congenital esotropia. The median age at esotropia onset for the 23 children with ANAET was 31.4 months (range, 8-63 months) with a mean initial angle of esotropia of 24 PD. Although at least 2 children presented with diplopia, none of the 23 patients were known to have harbored intracranial tumors or other lesions of the central nervous system during the follow-up period. Fourteen of the 19 patients who underwent surgery attended follow-up visits for at least 6 months after their last surgical procedure: 13 were within 8 PD or less of orthotropia, whereas the final patient had persistent esotropia. Twelve of the 13 patients within 8 PD of orthotropia demonstrated some level of stereopsis, including 2 children with bifoveal fixation. Two (10.5 %) of the 19 operated patients later required a low hyperopic spectacle correction to control their deviation. CONCLUSIONS: ANAET was more prevalent than congenital esotropia in this cohort of children with esotropia. This clinically distinct form of strabismus typically begins between 1 and 5 years of age and appears to be infrequently associated with underlying disease. The angle of deviation is relatively small and early surgical correction is more likely to achieve bifoveal fixation for these patients than for those with congenital esotropia.

Timely surgery in intermittent and constant exotropia for superior sensory outcome.

PURPOSE: To determine whether time of strabismus surgery for patients with acquired intermittent exotropia and constant exotropia influences postoperative sensory outcome. METHODS: In a retrospective, cross-sectional study, 76 patients with acquired intermittent or constant exotropia and motor realignment were evaluated for postoperative sensory status. Age at surgery, duration of exotropia, and presence of intermittent or constant exotropia were correlated with postoperative sensory status. The 23 male and 53 female patients had an average age of 9.3 years at the time of surgery and a mean follow-up of 5.9 years. RESULTS: Patients had a significantly greater chance of having postoperative stereoacuity better than 60 seconds of arc (bifixation) if they were surgically aligned before 7 years of age (P <.01) or before 5 years of strabismus duration (P <.05), or with intermittent as compared with constant exotropia (P <.001). Patients with postoperative bifixation had earlier surgical intervention (P <.025) and shorter duration of exotropia (P <.025) than those with postoperative monofixation. CONCLUSIONS: Patients with intermittent or constant exotropia may achieve superior sensory outcome with motor realignment before age 7, before 5 years of strabismus duration, or while the deviation is intermittent.

Second nonocular tumors in survivors of heritable retinoblastoma and prior radiation therapy.

PURPOSE: The principal objectives of this study were to estimate the incidence of second tumors among children treated for heritable retinoblastoma during a 50-year period and to investigate the relationship between these tumors and previous radiation therapy. METHODS: The records of all retinoblastoma patients examined at the Mayo Clinic from 1941 through 1990 were retrospectively reviewed. The therapeutic modality used to manage the tumor, the occurrence of any second malignancy, and current follow-up on all patients were evaluated. RESULTS: Eighty-two (46%) of 180 children with retinoblastoma had bilateral tumors (76 patients) or unilateral disease and a positive family history (six patients) and were followed for an average of 21.8 years (range, 1 month to 53 years). The Kaplan-Meier estimates of second nonocular tumors among the 82 patients with heritable retinoblastoma were 12% at 10 years, 16% at 25 years, and 30% at 40 years. Although 14 of the 15 patients who developed second malignancies had received radiation therapy, only four of the malignancies occurred within the field of irradiation. CONCLUSIONS: The relatively low incidence of second tumors among long-term survivors of heritable retinoblastoma in this series of patients occurred predominantly outside the field of irradiation. The variable incidence of second nonocular malignancies in previous reports may reflect variations in radiation technique and dosage.

Congenital esotropia in Olmsted County, Minnesota.

OBJECTIVE: To determine the birth prevalence of and risk factors associated with congenital esotropia. DESIGN: Population-based prevalence study with nested case-control study. PARTICIPANTS: All residents of Olmsted County, Minnesota who were diagnosed with congenital esotropia and born between January 1, 1980 and December 31, 1989 (n = 47). Control subjects were chosen by selecting the next two sequential births to parents residing in Olmsted County, Minnesota (n = 94). METHODS: Cases were identified through the Medical Diagnostic Index of Mayo and the Rochester Epidemiology Project. The community medical records were reviewed to confirm case status and ascertain risk factor information. MAIN OUTCOME MEASURE: Birth prevalence of congenital esotropia. RESULTS: Forty-seven cases were identified from 17,536 live births, for a birth prevalence of 27 per 10,000 (95% confidence interval [CI], 20-35). Congenital esotropia was associated with prematurity (odds ratio [OR], 11.5; 95% CI, 3.4-39.2), a birth weight less than 2500 grams (OR, 4.6; 95% CI, 1.7-12.9), a low Apgar score at 1 minute (OR, 4.3; 95% CI, 1.7-11.2) and at 5 minutes (OR, 6.3; 95% CI, 1.3-30.7), and a family history of strabismus (OR, 3.5; 95% CI, 1.5-8.3). CONCLUSIONS: The birth prevalence of congenital esotropia in Olmsted County, Minnesota is lower than previous estimates. Prematurity, low birth weight, low Apgar scores, and a family history of strabismus are significant risk factors for congenital esotropia.

Acquired posterior lentiglobus.

PURPOSE/METHODS: An infant examined by three ophthalmologists was found to have unilateral posterior lentiglobus, which subsequently developed bilaterally by 15 weeks of age. RESULTS/CONCLUSIONS: The onset of posterior lentiglobus may be congenital or acquired. Infants with unilateral cataracts whose family history indicates early-onset lens opacities require careful and frequent examinations of the fellow eye.

Ancillary testing for metastasis in patients with newly diagnosed retinoblastoma.

PURPOSE: The primary objective of this study was to determine whether ancillary testing for metastasis is justified in the routine examination of patients with newly diagnosed retinoblastoma. METHODS: The records of all patients with retinoblastoma diagnosed at the Mayo Clinic from 1952 through 1989 or examined within two months of diagnosis elsewhere were reviewed. The ancillary tests used to detect metastatic disease, available histopathologic specimens, and five-year follow-up were recorded on all patients. RESULTS: We identified 100 patients, with newly diagnosed retinoblastoma, who were ultimately followed up for at least five years after diagnosis or until death. Of the 100 patients, 35 underwent bone marrow aspiration, lumbar puncture, or both, within one month of diagnosis. Results of all ancillary tests performed in these 35 patients were negative for metastatic disease. Nine of the 35 patients had choroidal extension and two had retrolaminar involvement. Although one patient developed orbital recurrence that was successfully treated with exenteration and chemotherapy, none of the 35 patients died of metastatic retinoblastoma in a mean follow-up period of 9 1/2 years. The overall survival free of metastasis from retinoblastoma in these 100 patients was 97% at five years (95% confidence interval: 94% to 100%). CONCLUSIONS: The routine use of bone marrow and lumbar puncture studies in the examination of all patients with newly diagnosed retinoblastoma cannot be supported by this study.