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Background Evaluation of neurocognitive outcomes after a treatment strategy of chemotherapy followed by reduced-dose and volume irradiation for primary central nervous system (CNS) germinoma. Methods Neuropsychological evaluations including measures of verbal and nonverbal intellectual functioning, working memory, processing speed, verbal and nonverbal memory, executive functioning, depression, anxiety, and social functioning were analyzed for all patients (N = 20) with histologically diagnosed CNS germinoma diagnosed at our institution between 2003 and 2009. All 20 patients underwent at least one neuropsychological evaluation, 14 patients had at least two evaluations, 7 patients had at least three, and 2 had four, generating a total of 43 test batteries at a mean of 3.0 years from diagnosis. Results The 20 patients performed as a group in the average range on all neurocognitive measures administered when compared to the nonmedical normative group. No decline over time was indicated on any of the neurocognitive measures. An improvement over time was indicated for nonverbal reasoning, nonverbal memory, processing speed, working memory, response inhibition, and cognitive flexibility. No significant differences were found by tumor location, age at diagnosis, or hydrocephalus at presentation. Conclusions For pediatric and adolescent patients with newly diagnosed CNS germinoma, modest chemotherapy followed by reduced dose ventricular field irradiation with simultaneous integrated boost to the primary site, is associated with preservation of neurocognitive, social and emotional functioning. Pediatr Blood Cancer 2011; 57: 669–673. © 2011 Wiley-Liss, Inc.

To explore the associations of general health-related quality of life (GHRQOL) with strabismus or amblyopia in preschool children.Population-based study.Sample of children aged 25 to 72 months in the Multi-ethnic Pediatric Eye Disease Study (MEPEDS).The Pediatric Quality of Life Inventory (PedsQL), a measure of GHRQOL, was administered to the parents of the children.The PedsQL consists of 4 subscales (physical, emotional, social, and school functioning) and 3 composite scores (physical summary, psychosocial summary, and total). Regression models were used to evaluate the associations of GHRQOL with strabismus (in children 25-72 months) or amblyopia (in children 30-72 months).Of the 4218 children aged ≥25 months, 121 (2.9%) were diagnosed with strabismus. Significant differences were found in all 3 composite scores between children with and without strabismus, before and after controlling for gender, age, race, family income, systemic health conditions, and prior knowledge of strabismus diagnosis (P0.05). These differences were present in esotropes, exotropes, children with intermittent strabismus, and children with constant strabismus. A total of 3318 children were aged ≥30 months, and 71 children (2.1%) had amblyopia. There were no significant differences in any PedsQL scores between children with and without amblyopia, even after adjusting for gender, age, race, and family income (P0.05).Strabismus was associated with significantly worse GHRQOL in preschool children. Although we did not find any detectable association between amblyopia and GHRQOL, further study using vision-specific instruments is required to explore the impact of both strabismus and amblyopia on pediatric quality of life.

To determine the age-, gender-, and ethnicity-specific prevalence of astigmatism in African American and Hispanic children aged 6 to 72 months.Population-based, cross-sectional study.The Multi-Ethnic Pediatric Eye Disease Study is a population-based evaluation of the prevalence of vision disorders in children ages 6 to 72 months in Los Angeles County, California. Seventy-seven percent of eligible children completed a comprehensive eye examination. This report provides the results from 2994 African American and 3030 Hispanic children.Eligible children in 44 census tracts were identified during an in-home interview and scheduled for a comprehensive eye examination and in-clinic interview. Cycloplegic autorefraction was used to determine refractive error.The proportion of children with astigmatism defined as cylindrical refractive error ≥ 1.50 diopters (D) in the worse eye. The astigmatism type was defined as with-the-rule (WTR) (+ cylinder axis 90 ± 15 degrees) and against-the-rule (ATR) (+ cylinder axis 180 ± 15 degrees); all other orientations were considered oblique (OBL). The prevalence of astigmatism and its types were also determined for worse eye cylindrical refractive error ≥ 3.00 D.Prevalence of astigmatism ≥ 1.50 D was higher in Hispanic children compared with African American children (16.8% vs. 12.7%, respectively; P0.0001). Hispanic children also showed a higher prevalence of astigmatism ≥ 3.00 D than African American children (2.9% vs. 1.0% respectively; P0.0001). The prevalence of astigmatism ≥ 1.50 D showed a significant decreasing trend with age (P0.0001). The prevalence of WTR, ATR, and OBL astigmatism ≥ 1.50 D was 13.9%, 0.6%, and 2.2%, respectively, in Hispanic children, and 7.8%, 2.2%, and 2.7%, respectively, in African American children.We observed ethnicity-related differences in astigmatism prevalence in preschool children. The age-related decrease in astigmatism prevalence in preschool children likely reflects emmetropization.

Carnivore consumption of fruit is a principle means by which many fleshy-fruited plant species achieve long-distance seed dispersal. We examined carnivore dispersal of hollyleaf cherry (Prunus ilicifolia) seeds, specifically assessing the survival, desiccation sensitivity, and germination of seeds found in bear scats. Studies were conducted both in the laboratory and in 2 burn areas in Los Padres National Forest, California. Bear scats containing P. ilicifolia seeds were collected in burned and unburned chaparral. We counted seeds in each scat and noted whether endocarps had tooth punctures or rattled audibly when shaken. For comparative germination trials, we also collected fruits and seeds directly from mature shrubs. In the laboratory, following a cold-moist stratification period, seeds were assessed for germinability. In the field, we compared desiccation rates and germinability of seeds from bear scats and freshly collected seeds. We compared rates of moisture loss and germination for seeds...

We investigated California black oak (Quercus kelloggii Newberry) acorn dispersal by rodents and birds in the months after a stand-replacing fire in a mixed conifer forest in the San Bernardino Mountains of southern California, USA. The objective of this study was to compare scatter-hoarding in a high-severity burn to that in an unburned forest. In the fall of 2007, we placed 600 magnet-bearing acorns under trees in the unburned area. Of the 600, we recovered 77 (13%). Dispersers moved acorns an average distance of 5 m and buried them to an average depth of 30 mm. By spring of 2008, 90% of the cached acorns were missing. In the high-severity burn, we recovered 59 (9.8%) of the 600 acorns placed under top-killed oaks; these had been scatter-hoarded an average of 5.27 m from the source plots and buried an average of 22 mm. By spring of 2008, 55% these acorns were missing, and many of those that we relocated had been re-cached in new locations. Our results suggest that scatter-hoarding of acorns may be a common phenomenon after fire, and likely plays an important role in seedling recruitment.

Background/aims Children with optic nerve hypoplasia (ONH) have visual impairment and may have hypopituitarism and developmental delay. Children with ONH have also been reported to have abnormal sleepewake cycles. We assessed the incidence and nature of sleepewake abnormalities in children with ONH. Methods Resteactivity patterns were assessed in 23 children with ONH using actigraphy, which is a noninvasive method for continuously monitoring activity. The children also had formal assessment of pituitary function, visual acuity measurements, assessment of papillary responsiveness, MRI scans of the head and assessment of neurocognitive function. Results Sufficient actigraphy data were obtained on 19 of the children. Analysis of expressed rhythmicity revealed normal resteactivity patterns in 13 children (68%). Of the six children (32%) with abnormal rhythmicity, three had fragmented sleep, one had freerunning resteactivity cycles and two were arrhythmic. Of the children with normal rhythmicity, the following were found: hypoplastic corpus callosum in 30%, growth hormone deficiency in 53%, hypothyroidism in 23%, adrenal insufficiency in 30%, diabetes insipidus in 0% and developmental delay in 15%. Of the children with abnormal rhythmicity, the following were found: hypoplastic corpus callosum in 66% (p>0.05), severe visual impairment in 100% (p¼0.006), abnormal pupillary responsiveness in 85% (p¼0.0084), cognitive impairment in 100% (p¼0.04) and multiple hormonal deficiencies in 66% (p¼0.03). Conclusions Abnormal resteactivity rhythmicity patterns are present in 30% of children with ONH. The best predictors of abnormal rhythmicity are severe vision impairment, abnormal pupillary responsiveness, developmental delay and multiple hormonal deficiencies.

Bigcone Douglas-fir (Pseudotsuga macrocarpa [Vasey] Mayr) is a long-lived, fire-adapted conifer that is endemic to the Transverse Ranges of southern California. At the lower and middle reaches of its elevational distribution, isolated stands of bigcone Douglas-fir are surrounded by extensive stands of chaparral. Our dendrochronology investigations have revealed that these ancient trees commonly record multiple past fires as fire scars in their lower boles. We hypothesized that the fire-scar record found within and among bigcone Douglas-fir stands reflects the temporal and spatial patterns of fire in the surrounding chaparral. We compared the fire scar results with independent, twentieth century fire atlas data to assess our interpretations. Using fire scars and ring-growth changes, we reconstructed fire history in Los Padres National Forest and investigated changes in fire regime characteristics over the past several centuries. Our analyses confirm that the tree-ring record can be used to accurately reconstruct past fire occurrence and extent patterns both within bigcone Douglas-fir stands and surrounding chaparral stands. Many extensive fires were apparent in both the pre- and post-twentieth century period indicating that such events were a natural component of the system. However, many smaller fires were also evident in the tree-ring record, and more of these types of events occurred during the nineteenth century (and earlier) than during the twentieth century. We also identified a shift after the late nineteenth century to potentially more severe fires within and among stands, and by inference the surrounding chaparral. These findings suggest that land management policies, rates of human-set fires, or climatic variations may have played a role in shaping the contemporary fire regime, and that this recent period is different in some respects from the pre-twentieth century regime. Replication of this work in other mountain ranges, in addition to comparisons with climate and human histories, will provide valuable insights into our understanding of the relative roles of humans versus climate in changing bigcone Douglas-fir and chaparral fire regimes.

The purpose of the study is to characterise retinal function using light-adapted electroretinograms (ERGs) in a series of young children with ONH, congenital dysplasia of retinal ganglion cells. ERGs were recorded with chloral hydrate sedation in 27 children with ONH (18 with bilateral and 9 with unilateral ONH, age 4-35 months) and an adult reference population (n = 12). Stimuli included ISCEV standard flash, oscillatory potentials (OPs) and standard flicker as well as a light-adapted luminance-response series (photopic hill). The disc diameter to disc macula (DD:DM) ratio was measured from fundus photographs. The results are eyes with ONH, classified by DD:DM, were severe (or=0.15, n = 22), moderate (0.16-0.30, n = 22), mild (0.31-0.35, n = 1), and fellow eyes (0.35, n = 9), all had prolonged ERG implicit times and smaller i-waves than those of adults. Eyes with moderate or severe ONH also had smaller amplitudes for OPs and flicker ERGs and required stronger flashes to obtain the peak b-wave amplitude. Abnormalities of the photopic hill were a common but inconsistent feature of ONH and were not indicative of ONH severity. Abnormalities of the photopic hill of the ERG suggest that some cases of ONH may have retinal dysfunction with specific deficits in the ON or OFF pathways of the retina. ONH is a complex and heterogeneous condition that may involve dysfunction distal to the retinal ganglion cells.

Purpose To compare the clinical assessment of fixation preference (FP) to visual acuity (VA) in a population-based sample of preschool children with amblyopia risk factors. Design Evaluation of diagnostic test in a population-based study. Participants Two hundred forty-three children with amblyopia and/or strabismus, aged 30–72 months, living in Los Angeles County, California. Methods Before measuring VA, FP testing was performed at near and usually without correction, using the binocular fixation pattern in children with strabismus >10 prism diopters (Δ), or the induced tropia test for children with strabismus ≤10Δ or without strabismus. We determined the sensitivity and specificity of FP testing for predicting unilateral amblyopia, defined by optotype VA, among children with amblyopia risk factors. Main Outcome Measure Grade of FP. Results Sensitivity of FP testing for amblyopia among children with anisometropia was 20% (9/44) and specificity was 94% (102/109). Among strabismic children, sensitivity was 69% (9/13; worse in children 30–47 than 48–72 months old) and specificity was 79% (70/89), with similar findings for esotropia and exotropia. Conclusion The ability of FP testing to correctly identify amblyopia in preschool children with amblyopia risk factors is poor. Clinicians should be wary of using FP as a surrogate measure of interocular difference in VA in young children. Financial Disclosure(s) The authors have no proprietary or commercial interest in any materials discussed in this article.

The congenital malformation known as optic nerve hypoplasia (ONH) has been recognized in the past 30 years as an epidemic cause of congenital blindness. It was believed to occur either as an isolated anomaly or as a component of the syndrome of septo-optic dysplasia, which has evolved to include midline brain malformations and hypopituitarism. Evidence now suggests that ONH infrequently occurs in isolation. Most afflicted children will have hypothalamic dysfunction and/or neurodevelopmental impairment, regardless of MRI findings or severity of ONH. Adverse outcomes can often be ameliorated with early intervention. Thus, the syndrome of ONH should be suspected in all infants with signs of hypothalamic dysfunction or vision impairment.

BACKGROUND. Developmental delay has been reported to occur with optic nerve hypoplasia, a leading cause of pediatric blindness, but has not been systematically examined for its prevalence and correlation with associated pathologies of optic nerve hypoplasia.OBJECTIVE. The purpose of this study was to determine the developmental outcomes of children with optic nerve hypoplasia and the correlation of development with neuroradiographic, endocrinologic, and ophthalmic findings.METHODS. We conducted a prospective analysis of 73 subjects diagnosed with optic nerve hypoplasia at RESULTS. At 5 years of age, developmental delay was present in 71% of subjects with optic nerve hypoplasia. Of patients with unilateral (18%) and bilateral optic nerve hypoplasia, 39% and 78%, respectively, experienced developmental delay. Corpus callosum hypoplasia and hypothyroidism were significantly associated with poor outcome in all of the developmental domains and an increased risk of delay. Absence of the septum pellucidum was not associated with adverse development. Six subjects had neither a neuroradiographic nor an endocrinologic abnormality, and of those, 4 were developmentally delayed.CONCLUSIOONS. These prospective data confirm the significant association of developmental delay with optic nerve hypoplasia and identify corpus callosum hypoplasia and hypothyroidism as strong correlates. A diagnosis of optic nerve hypoplasia warrants neuroradiographic and endocrinologic testing for risk factors of delay and developmental assessments for early intervention planning.

Purpose To investigate the rate of spontaneous resolution of strabismus in patients with cortical visual impairment (CVI) at a single center over a 10-year period and to evaluate the success rate of strabismus surgery. Methods The medical records of patients with CVI and strabismus seen between October 2003 and October 2013 were reviewed retrospectively. Patients were classified into 4 outcome groups: (1) those who experienced spontaneous resolution of strabismus, (2) those with persistent strabismus who did not undergo surgery, (3) those who achieved postoperative alignment of ≤10 Δ ; and (4) those whose final postoperative alignment was 11 Δ -25 Δ or >25 Δ . Results A total of 70 patients were included. Of these, 11 patients (16%) experienced spontaneous resolution of strabismus, 27 (38%) were observed without receiving surgery, and 32 (46%) underwent strabismus surgery. Of these 32, 18 (56%) achieved alignment of ≤10 Δ ; 9 (28%), alignment of 11 Δ -25 Δ ; and 5 (16%), alignment >25 Δ . The patients who did not undergo surgery were significantly older at presentation (36 months vs 12-15 months; P = 0.03); otherwise, there were no significant differences between groups in age at surgery or spontaneous resolution, type of strabismus, or underlying cause of CVI. Conclusions In our study cohort, a minority of patients with CVI and strabismus (16%) experienced spontaneous resolution of strabismus. Only 16% of patients undergoing surgery had poor final alignment (>25 Δ ). Strabismus surgery can be reasonably successful in properly selected patients with CVI and strabismus. These patients show considerable rates of resolution of their strabismus, either spontaneously or through surgery.

A patient with adenosine deaminase–deficient severe combined immune deficiency (ADA-SCID) was enrolled in a study of retroviral-mediated ADA gene transfer to bone marrow hematopoietic stem cells. After the discontinuation of ADA enzyme replacement, busulfan (75 mg/m2) was administered for bone marrow cytoreduction, followed by infusion of autologous, gene-modified CD34+ cells. The expected myelosuppression developed after busulfan but then persisted, necessitating the administration of untransduced autologous bone marrow back-up at day 40. Because of sustained pancytopenia and negligible gene marking, diagnostic bone marrow biopsy and aspirate were performed at day 88. Analyses revealed hypocellular marrow and, unexpectedly, evidence of trisomy 8 in 21.6% of cells. Trisomy 8 mosaicism (T8M) was subsequently diagnosed by retrospective analysis of a pretreatment marrow sample that might have caused the lack of hematopoietic reconstitution. The confounding effects of this preexisting marrow cytogenetic abnormality on the response to gene transfer highlights another challenge of gene therapy with the use of autologous hematopoietic stem cells.

Large-seeded pines ( Pinus spp.) are known to be dispersed by seed-caching corvids (i.e. jays and nutcrackers) and rodents (e.g. chipmunks and mice), with a concomitant decrease in seed dispersability by wind. We tested the idea that seeds of bigcone Douglas-fir ( Pseudotsuga macrocarpa ), which are winged but larger than the seeds of other members of Pseudotsuga , are dispersed by a combination of wind and seed-caching rodents. We compared characteristics of seeds from P. macrocarpa in southern California (mean seed mass 132.6 mg) to seeds of a population of Pseudotsuga menziesii (Douglas-fir) in northern California (24.8 mg). We also tested whether rodents would cache seeds of P. macrocarpa . Seeds of P. macrocarpa had greater wing loadings (1.37 mg/mm 2 ) and descent velocities (2.47 m/s) than those of P. menziesii (0.52 mg/mm 2 and 1.28 m/s, respectively). These data indicate that the wind dispersability of P. macrocarpa is likely to be less than that of P. menziesii , but this loss of wind dispersability is partially compensated for by secondary dispersal of seeds by rodents, which readily gathered and cached the larger seeds of P. macrocarpa up to 34 m from source trees. Large seed size confers several advantages to P. macrocarpa , most importantly attracting seed-caching animals that effectively bury seeds.

For numerous species in fire-prone ecosystems, the passage of fire triggers the release of large quantities of seeds within 2 years of the fire. This special case of masting has been described for species in an array of floras, but few studies have followed the fates of seeds liberated into the postfire environment. In this study, I followed the fates of 990, magnet-bearing Marah macrocarpus seeds sown at three seed densities in a large, high-intensity burn area. Seeds disappeared over 6.6 months and removal at all three densities became negatively density-dependent in late summer until all seeds disappeared in mid winter. I recovered only 5% of the magnets, mostly from rodent tunnels. Based on the recovery of magnets, I estimate rodents moved ~91% of the seeds belowground. Seed burial trials showed that seedlings established from seeds buried up to 16 cm whereas seeds sown on the surface did not germinate. Seedlings also readily established from burial in soils with 50% rock fragments as well as from artificial tunnels in both pot and field experiments. Excavation of 50 natural seedlings suggested up to 20% established in rodent burrows. Findings of this study suggest that ecologists may have underestimated the role of burrows as locations for recruitment of large-seeded species.

Objective To determine the prevalence of endocrinopathies, neuroradiographical findings, and growth derangements in young children with optic nerve hypoplasia (ONH). Study design A prospective observational study examined the prevalence of endocrinopathies at study enrollment and growth patterns in children with ONH. Subjects (n = 47, mean ± SD 15.2 ± 10.6 months) were followed until 59.0 ± 6.2 months of age. Results The prevalence of endocrinopathies was 71.7%: 64.1% of subjects had growth hormone (GH) axis abnormalities, 48.5% hyperprolactinemia, 34.9% hypothyroidism, 17.1% adrenal insufficiency, and 4.3% diabetes insipidus (DI). Endocrinopathies were not associated with ONH laterality, absence of the septum pellucidum, or pituitary abnormalities on neuroimaging. End height standard deviation score (SDS) was similar to start length SDS independent of GH surrogate status. A significant increase in end weight SDS was found for the cohort (p 85th percentile was noted in 44.4% of the cohort and in 52.1% of subjects with GH axis abnormalities. Initial hyperprolactinemia was positively associated with increased end BMI SDS (p = .004). Conclusions These prospective findings confirm the high prevalence of pituitary endocrinopathies in children with ONH reported in previous retrospective studies. Our data reveal that some of these children maintain normal height velocity despite GH axis abnormalities, and, as a group, they are at high risk for increased BMI.

We wished to determine whether Resonant Raman Spectroscopy (RRS) could be used to measure Amphotericin B (AmB) at therapeutic and subtherapeutic concentrations in a model system mimicking the anterior chamber of the eye. The goal was to develop a technique for non-invasive measurement of AmB levels in the aqueous humor (AH) of the eye. A krypton-ion laser source (406.7 nm) was used for excitation and Resonant Raman Spectra were captured with a confocal system in an anterior chamber (AC) model. These spectra were used to develop a correlation curve for prediction of AmB levels. Subsequently, one rabbit was evaluated with this system after 5 days of intravenous AmB administration (1 mg/kg/day) and AmB concentrations measured by RRS were compared to those measured by high-performance liquid chromatography (HPLC). AmB exhibited a unique spectral peak at 1557 cm(-1). Integrated area of this peak linearly correlated with AmB concentration in our model AC. When integrated peak area from multiple in vivo measurements in one animal at steady-state was plotted on this correlation curve, we were able to predict AmB levels. These closely approximated those measured by HPLC. These measurements were not significantly affected by photobleaching or depth profile at acquisition. RRS at 406.7 nm is a method that may be useful for non-invasive monitoring of intraocular AmB levels. This instrument can help physicians decide when repeat, invasive delivery of this drug is warranted based on measurement of actual drug levels in the AH. Also, there is the potential to measure the ocular concentrations of other pharmaceutical agents with similar instruments.

The International Commission on Non-Ionizing Radiation Protection (ICNIRP) established eye-safe exposure limits for laser light based on estimates of the 50% exposure dose (ED50) for retinal damage in animals. The ED50 has not been determined for continuous-wave near-infrared (NIR) light, as may be used in instruments for spectroscopic analysis of the eye. The purpose of this study is to determine the ED50 of 785-nm light delivered by a Raman spectroscopy instrument on the retinas of pigmented rabbits, and to compare that ED50 to the ICNIRP estimates. Light of varying power was focused into the anterior chambers of rabbits for 4, 20, or 300 s. Estimates of spot size on the retina were determined by modifying the schematic rabbit eye with actual axial length and refractive error measurements. Masked examiners determined retinal burns from fundus photographs and fluorescein angiograms made immediately after exposure and again 48-72 h later. Thirty-five of 86 exposed eyes had retinal burns. In 12 of these the burn was not visible until 48-72 h. In 6 the burn was visible on color photographs, but not on fluorescein angiography. The ED50 retinal power density from probit analysis was 14,513 mW cm - 2 , 10,369 mW cm - 2 , and 5,237 mW cm - 2 for 4-s, 20-s, and 300-s exposures, respectively. Thus, the ED50 for retinal burns from 785-nm light is approximately 7 and 7.5 times the ICNIRP permitted limits for 4- and 20-s exposures, and 5.6 times the limit for 300-s exposures. This is consistent with the ICNIRP intention to set power limits several times less than ED50.

The geophytic, perennial vine Marah macrocarpus resprouts vigorously from an underground tuber after chaparral fires and produces numerous large (1,400 mg), non-dormant seeds. Studies of the postfire response of M. macrocarpus were conducted at two sites. At the main study site, the number of stems per plant was highest in the first 2 y after fire but declined rapidly in the third year. Seed yield peaked in the first year and was estimated to be about 8,469 seeds·ha-1. The largest plants produced seeds, but despite prolific resprouting and growth, only 22% of the population set seed. Most seeds fell within 1.3 m of the centre of the parent plant. Over a 3-y period, I tracked the fate of magnet-bearing seeds. Rodents, primarily Dipodomys agilis and Peromyscus spp., dispersed and cached seeds in the burn area 13.6 ± 9.5 m (mean ± SD) from parent plants. In the first year, four seedlings (2%) established from 200 marked seeds; all seedlings originated from multi-seed rodent caches. In the second yea...

Seedling recruitment in many highly serotinous populations of Pinus coulteri on California's central coast depends almost entirely on periodic, stand-replacing fire. Compared to serotinous pines of the Mediterranean Basin, little detailed information is available on the postfire demography of California closed-cone pines, including P. coulteri. In September 1996 a wildfire burned the 760-ha American Canyon Research Natural Area (RNA). Using aerial photography, we mapped burn severity of P. coulteri-chaparral woodlands and forests within the RNA. From May to September of 1997, we also quantified seedling establishment and mortality in relation to biophysical site characteristics including fire severity. Seventy-six percent of P. coulteri forests and woodlands experienced high-severity burns, 9% moderate-severity burns, and 15% low-severity or unburned. Of the 53 plots used for seedling counts, 70% were high-severity, 26% moderate-severity, and 4% low-severity. Seedling densities 13 months postfire were low (0.21 m−2), but seedling mortality also was low (8.4%). Aerial seed bank size increased from north-facing to south-facing slopes and from high-severity to low-severity burns. Seedling recruitment was unrelated to burn severity and increased with the size of the canopy seed bank (cone density). Many seedlings established from rodent seed caches; 23% of the seedlings established in clumps from seeds cached by Dipodomys agilis, Chaetodipus californicus and Peromyscus maniculatus. Pinus coulteri seeds have low potential for dispersal by wind, but secondary dispersal by rodents moves seeds away from source trees and into neighboring chaparral. We discuss the potential importance of rodent seed caching to postfire demography of California and Mediterranean serotinous pines.

The seed-dispersal systems of Coulter pine (Pinus coulteri), gray pine (P. sabiniana), and Torrey pine (P. torreyana), all of the subsection Sabinianae, are not well understood. These pines occur in arid and semi-arid foothills and mountains of California that are subjected to frequent fires. Cone and seed traits of these three California pines are compared to those of four species of pines (sugar pine, P. lambertiana; Jeffrey pine, P. jeffreyi; ponderosa pine, P. ponderosa; and lodgepole pine, P. contorta) that occur in more mesic environments in the nearby Sierra Nevada mountains. The cones of the Sabinianae pines are large with thick, dense scales, and the scales of gray and Coulter pines are armed with sharp, recurved spines. The seeds of all three species are large, and those of gray and Torrey pines are nearly wingless. In contrast, the Sierra Nevada pines have small to medium-sized seeds with large wings that are initially dispersed by the wind. Heavy wing loading of the Sabinianae pine seeds causes them to fall rapidly, and they are not dispersed far by wind. However, animals remove the fallen seeds rapidly, and rodents and jays scatter hoarded many seeds in the soil. This caching activity results in seedling establishment. The unusual morphology of the cones and seeds of the Sabinianae pines is interpreted as a combination of traits that attract animal dispersers, thwart the foraging activities of seed predators, and promote the survival of seeds in an environment subject to frequent fires.

Zigadenusfremontii is often a striking component of the flora following firein the chaparral. Like other geophytes, it produces large numbers of flowers inthe first spring after a burn. Although these plants are most conspicuous intheearly postfire environment, the question that remains is, how do they persistinthe interval between fires? To address this we investigated differences in thegrowth and reproduction of Z. fremontii in burned andunburned chaparral. We monitored marked individuals for nine years at threesites: two that were burned in 1990 and one in the same area that was inunburned mature chaparral. We measured leaf area, and production of flowers andfruits. We also conducted seed experiments in the field to determine the ratesand timing of germination. We found that reproduction occurs only in theimmediate postfireperiod: flowering and production of fruits and seeds in the first yearfollowingfire, and seedling establishment by year 3. There was a cost of reproduction;plants that flowered (in the burn area) had negative growth rates the followingyear. In contrast, plants in unburned chaparral, which did not flower, hadpositive growth rates over the same period. Moreover, plants that produced themost flowers had the lowest growth rates. In the unburned chaparral site,plantswere not dormant as predicted from previous literature; instead they producedleaves nearly every year. In most years the average leaf area per plant wasgreater than that in the burned sites. Our results indicate that postfirereproduction depends on growth and carbohydrate storage in the inter-fireperiod. We also suggest that this species is relatively long-lived for aherbaceous perennial.

Factors related to the survival of Coulter pine (Pinus coulteri) and gray pine (P. sabiniana) 3 yr after a September wildfire were evaluated for a site on the central coast of California. Data for 146 Coulter pine and 117 gray pine were analyzed with logistic regression models to estimate postfire survival in relationship to tree and fire-damage variables. Probability of survival for both species decreased with the increasing percentage of crown scorching and increasing height of bole bark char. Crown scorch was the most important variable for predicting survival of these species, but it was augmented by the bole-damage variable. Survival of gray pine was higher than that of Coulter pine for comparable values of both variables. West. J. Appl. For. 17(3):134–138.

Objective. Opsoclonus-ataxia, also called “dancing eye syndrome,” is a serious neurologic condition that is often a paraneoplastic manifestation of occult neuroblastoma in early childhood. Despite resection of tumor and immunosuppressive therapy, outcome generally includes significant developmental and behavioral sequelae. There is controversy about how treatment alters outcome. The goals of this study were to understand the ongoing neurologic and developmental deficits of children who are treated for opsoclonus-ataxia with associated neuroblastoma; to relate treatment history to outcome; and to quantify objectively the acute changes in motor function, speech, mood, and behavior related to intravenous immunoglobulin (IVIg) treatment. Methods. Patients were children with opsoclonus-ataxia caused by neuroblastoma, regardless of interval since diagnosis. Records were reviewed, and children underwent comprehensive evaluations, including neurologic examination and tests of cognitive and adaptive function, speech and language, and fine and gross motor abilities. Psychiatric interview and questionnaires were used to assess current and previous behavior. In 6 children, a videotaped standardized examination of eye movements was performed. Additional examinations were performed immediately before and 2 to 3 days after treatment with IVIg in 5 children. Results. Seventeen children, ages 1.75 to 12.62 years, were examined. All had a stage I or II neuroblastoma resected 3 months to 11 years previously. None received any other treatment for the tumor. All but 1 had received at least 1 year of either oral corticosteroids or corticotropin (ACTH); 12 had received 1 or more courses of IVIg, 2 g/kg. Three had received other immunosuppressive treatment, including cyclophosphamide. Cognitive development and adaptive behavior were delayed or abnormal in nearly all children. Expressive language was more impaired than receptive language. Speech was impaired, including both intelligibility and overall output. Fine and gross motor abilities were impaired. Increased age was strikingly associated with lower scores in all areas. Behavioral problems early in the course included severe irritability and inconsolability in all; later, oppositional behavior and sleep disorders were reported. Opsoclonus abated in all, but abnormalities in pursuit eye movements were found in all 6 children cooperative with standardized examination. Outcome did not differ in children who were treated with ACTH versus oral steroids. Three children who had received cyclophosphamide fared poorly. Immediate versus delayed treatment was not associated with better outcome. IVIg improved both gross and fine motor and speech function acutely, but we could not confirm long-term benefit of IVIg. Total number of courses of IVIg was not associated with outcome. Conclusions. Opsoclonus-ataxia caused by neuroblastoma causes substantial developmental sequelae that are not adequately prevented by current treatment. The increased deficits in older children raise concern that this represents a progressive encephalopathy rather than a time-limited single insult. Although the study is cross-sectional and neither randomized nor blinded, we were unable to confirm a purported advantage of either ACTH over corticosteroids or of cyclophosphamide. A randomized study is needed but is difficult for this rare condition.

Many laboratories have been developing techniques that might be applied toward a non-invasive device that could optically measure aqueous humor glucose in the eye as a surrogate for blood glucose. We have configured a confocal Raman microscope that is capable of acquiring the Raman spectra of the aqueous humor in vivo. However, because of the potential for optical toxicity, a major design consideration is evaluating the tradeoff between the energy of exposure and measurement accuracy. Toward this end, we have developed a physical model of the anterior chamber in the eye for studying the feasibility of using a confocal Raman microscope for determining the concentration of glucose and other metabolites. The Raman spectrum of aqueous humor closely resembles the spectrum of its four primary Raman scatterers, (glucose, urea, lactate and ascorbate) mixed in normal saline. Aqueous mixtures of these analytes were placed under a contact lens resting on a quartz plate to form a physical model of the anterior chamber filled with aqueous humor. Calibration standards were prepared by non-collinearly varying the measured concentrations of the analytes over a range of 0–13 times the mean physiological levels found in aqueous humor. A confocal microscope was used to acquire spectra using an excitation wavelength of 785 nm. The accuracy to which the concentration with analytes could be optically measured was evaluated using the partial least-squares (PLS) algorithm and spectral datasets collected using exposure energies of 75, 150, 300, 900, and 1800 mJ. The optimum standard error of prediction (SEP) obtained for glucose was 34.3 mg dl−1 (2.72% of full range) using a 12-factor PLS model calculated using intensity-normalized spectra acquired over a free spectral range of 400–1800 cm−1 with 900 mJ excitation energy. Clinically acceptable predictability (4.6%) was obtained with 300 mJ total excitation energy. Similar results were obtained for urea (SEP = 8.84 mg dl−1, 1.88%), ascorbate (SEP = 17.1 mg dl−1, 8.22%) and lactate (SEP = 82.9 mg dl−1, 7.59%) using 900 mJ exposure. Our results suggest that Raman spectroscopy may provide a feasible method of non-invasive glucose measurement if ocular toxicity can be avoided. Copyright © 2002 John Wiley & Sons, Ltd.

To determine whether the ratio of optic disk diameter to disk-to-macula distance (DD/DM) in children with optic nerve hypoplasia (ONH) changes over time.Fifteen subjects (29 eyes) enrolled in a prospective registry study on ONH had fundus photography performed under the age of 24 months and again at 60 months. Using the ratio of the DD/DM method, the relative size of the optic disk was assessed twice for each photo by one masked expert examiner to determine whether any change in relative disk size occurred over time.There was no change in relative optic disk size between initial and final fundus photographs. The average (± SD) age at the time of initial and final fundus photography was, respectively, 11.6 ± 5.2 months and 60.6 ± 1.3 months. Strong concordance was noted between the average DD/DM of the initial and the final photographs (ρ=0.939; 95% CI: 0.893, 0.981). There was negligible difference between the individual time point measurements (-0.011 ± 0.03) (95% LOA: -0.07, 0.04).There were no clinically significant changes in relative optic disk size over time in children with ONH; thus, DD/DM measurements need not be adjusted by age beyond 1 year in children with this disorder.

Objective To define the spectrum of ophthalmic manifestations of Duane's retraction syndrome (DRS) in a large family. Design Cross-sectional study of 110 among 114 living relatives in an extended family. Methods History and ophthalmic examination obtained on all participants. Main outcome measures Ocular motility, strabismus, visual acuity, binocularity, associated neurologic problems. Results Twenty-five individuals were affected with DRS. Twenty-four subjects (96%) had bilateral DRS, but there was a broad spectrum of severity. Strabismus occurred in 76% and amblyopia in 48%. Associated findings included fourth cranial nerve palsy, partial third cranial nerve palsy, nystagmus, seizures, and deafness. Fourth cranial nerve palsies and manifest strabismus tended to cluster within single family units. Conclusions Strabismus and amblyopia are much more common with bilateral DRS than with unilateral DRS. There is much phenotypic variability among individuals within families with hereditary Duane's syndrome. The responsible gene(s) may affect the development of many cranial nerves. Genetic compounding may play a role in the phenotypic segregation seen within this large family.

Purpose: Visual deprivation disrupting binocular development, such as that occurring with congenital cataract, is reported to cause asymmetric monocular optokinetic nystagmus (MOKN), as well as poor sensory and motor fusional outcome. We wanted to determine if symmetric MOKN could develop in cases of congenital cataract with good fusional outcome. Methods: We tested MOKN (with video and electro-oculographic recordings) and stereoacuity on 5 patients with good visual acuity and satisfactory ocular alignment after surgery for congenital cataract. Results: Stereoacuity was better than 50 seconds of arc in 1 case of monocular cataract and 2 cases of bilateral cataract. These case patients had symmetric MOKN. In a monocular cataract case, symmetric MOKN was observed in spite of questionable stereoacuity (at least 500 arc/s). One patient showed asymmetric MOKN, despite good visual acuity, and stereoacuity of 200 arc/s. Conclusions: Patients with congenital cataract can have symmetric MOKN and good stereopsis. These cases suggest that MOKN symmetry develops along with good stereopsis, but the quality of stereopsis necessary for development of MOKN symmetry remains unclear. (J AAPOS 1999;3:221-6)

Background: Glucose in the aqueous humor appears to correlate with plasma glucose in humans. It is therefore a potential substrate for noninvasive optical glucose monitoring techniques. We wished to determine the potential for using rabbit aqueous humor as a model to develop a noninvasive method of measuring glucose with Raman spectroscopy. Methods: Aqueous humor from 32 rabbit eyes was removed immediately after sacrifice by rapid exsanguination under anesthesia. Raman spectroscopy was performed on the aqueous humor using near infrared (NIR) excitation wavelengths. The Raman spectra from 785 nm and 787.2 nm were subtracted one from the other to eliminate broadband fluorescence. The spectra were then analyzed with linear and nonlinear multivariate analysis and assessed for ability to predict actual aqueous humor glucose concentration. Nine other rabbits were anesthetized with xylazine in order to cause elevation of blood glucose by blocking release of insulin. Blood and aqueous humor glucose were measured ...

PURPOSE: To report the features of idiopathic intracranial hypertension in prepubertal children, with emphasis on presentation, treatment, and outcome. METHODS: We retrospectively reviewed the charts of all patients 11 years and younger diagnosed with idiopathic intracranial hypertension at two university-affiliated medical centers. Inclusion critera included papilledema, normal brain computed tomography or magnetic resonance imaging, cerebrospinal fluid pressure greater than 200 mm H 2 O, normal cerebrospinal fluid content, and a nonfocal neurologic examination except for sixth nerve palsy. Patients with concomitant systemic illness were excluded. RESULTS: Of the 10 patients, four were girls and six were boys. Only one patient was obese. The most common presenting symptoms were stiff neck (four patients) and diplopia (four patients), and the most common presenting sign was strabismus (eight patients). Six of eight patients with strabismus had abducens nerve palsy (four bilateral), one patient had a sensory exotropia, and one had a comitant esotropia. Visual field abnormalities were present in 11 of 13 eyes (85%), and severe visual loss resulting in no light perception vision occurred in one eye of one patient. Nine patients were treated medically, four with a combination of prednisone or dexamethasone and acetazolamide and five with acetazolamide alone. One patient in this group also required a lumboperitoneal shunt. One patient was treated with lumbar puncture only. Resolution of papilledema occurred rapidly in all patients, with a mean of 4.7 ± 2.6 months. Resolution of sixth nerve palsy also occurred rapidly in four of six patients in a mean of 1.6 ± 1.2 months. One patient required strabismus surgery for persistent esotropia and one was lost to follow-up. CONCLUSIONS: Idiopathic intracranial hypertension in prepubertal children is rare and is different than the disease in adults. In our series, there appeared to be no sex predilection, and obesity was uncommon. Children are likely to present with strabismus and stiff neck rather than headache or pulsatile tinnitus. Both papilledema and sixth nerve palsy resolved rapidly with treatment. However, children can sustain loss of visual field and visual acuity despite treatment.

Introduction: We wished to determine whether final visual acuity is dependent on age at optical correction or presence of esotropia in children with bilateral high hypermetropia. Methods: We reviewed the charts of all patients at Childrens Hospital Los Angeles Division of Ophthalmology with bilateral hypermetropia of greater than or equal to 5D who were able to provide objective visual acuity outcomes with Snellen letters or linear E. Results: One hundred thirteen patients met entry criteria. The age at first optical correction ranged from 8 months to 141 months (average 45 months). Initial visual acuity (before optical correction) was obtainable in 82 patients. Initial visual acuity ranged from 20 20 to 20 200 , with 57% of patients having acuity better than or equal to 20 40 . Final visual acuity (after optical correction) ranged from 20 20 to 20 70 , with 109 patients (96%) having acuity better than or equal to 20 40 and 104 patients (92%) having acuity better than or equal to 20 30 . There was no relationship between final visual acuity and age that spectacles were first worn. Ninety-five patients (84%) had esotropia with or without glasses, and six of these (6%) had final visual acuity less than 20 30 . Of the 18 patients with orthotropia, three (16%) had final visual acuity less than 20 30 . The prevalence of ametropic amblyopia in patients with esotropia and orthotropia was not significantly different (p = 0.18). Conclusion: Visual acuity outcome in children with high hypermetropia is generally good regardless of age at initial optical correction or presence of strabismus. A significantly increased risk for ametropic amblyopia was not found in those patients with orthotropia.

Objective: The purpose of the study is to review etiologies and outcomes of sudden, late-onset esotropia. Design: The authors reviewed charts of patients in whom acute, comitant, constant esotropia developed after 5 years of age. Main Outcome Measures: The authors evaluated final ocular alignment, treatment, fusion, apparent etiologies, and associated neurologic conditions. Results: Ten patients met entry criteria with documentation of previous orthotropia. Ages ranged from 5 to 35 years. Esotropia at near ranged from 16 to 70 prism diopters. In seven patients, the esotropia improved partially or completely with correction of hypermetropia. Eight patients required surgery. In only one patient were neuroimaging studies positive, associated ophthalmic and systemic findings identified, and underlying neurologic disease diagnosed. Conclusions: Sudden, late-onset esotropia may be caused by an uncorrected refractive error. If no other neurologic signs are present, underlying intracranial disease is unlikely.

LG-16. RADIOGRAPHIC AND OPHTHALMOLOGIC CHARACTERISTICS OF OPTIC PATHWAY GLIOMA IN CHILDREN WITH NEUROFIBROMATOSIS 1 Elizabeth Unterbrink1, Benita Tamrazi1,2, Mark Borchert1,2, Ashley Margol1,2, Linda Randolph1,2, Tena Rosser1,2, Girish Dhall1,2, and Nathan Robison1,2; Children’s Hospital Los Angeles, Los Angeles, CA, USA; University of Southern California Keck School of Medicine, Los Angeles, CA, USA OBJECTIVE: To describe the natural history of optic pathway glioma (OPG) in children with neurofibromatosis 1 (NF1). METHODS: The Children’s Hospital Los Angeles (CHLA) institutional review board approved this retrospective study. Using a clinical database, we identified children with NF1 and OPG followed at CHLAwith at least 1 MRI obtained at ,12 years of age from 6/1/1997-5/31/2014. Demographic, treatment, and visual field/ acuity data were extracted. MRIs were reviewed by a neuroradiologist. RESULTS: Of 63 children with NF1 and OPG, 50 had available imaging and were included. Mean age at initial MRI was 4.8 years; mean follow-up was 6.8 years. OPG was apparent on brain MRI in 4/7 children at ,2 years (57%; 95% confidence interval[95%CI] 20-94); 19/23 by 4 years (83%; 95%CI 67-98); 29/31 by 6 years (94%; 95%CI 85-100); and 50/50 by 12 years. Among 13 children (26%) who subsequently received tumor-directed treatment, OPG was MRI-apparent in 5/6 children by 4 years (83%; 95%CI 54-100), 8/9 by 6 years (89%; 95%CI 68-100) and 13/13 by 8 years. Among children with detailed visual outcome data, visual impairment was seen in 6/20 at , 4 years (30%; 95%CI 10-50); and 26/45 by 12 years (58%; 95%CI 43-72). A subset had normalization of vision, with persistent visual abnormalities in only 14/41 children on follow-up (34%; 95%CI 20-49). DISCUSSION: A minority of children without MRI-apparent OPG at initial evaluation eventually developed symptomatic disease. The high incidence of early-onset visual abnormalities highlights the importance of early NF1 diagnosis and ophthalmologic screening. Neuro-Oncology 18:iii78–iii96, 2016. doi:10.1093/neuonc/now075.16 #The Author(s) 2016. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Background: Optic nerve hypoplasia (ONH) has developed into a leading cause of congenital blindness. The frequently associated features of hypopituitarism and absent septum pellucidum were felt to have embryonic linkage as “septo-optic dysplasia” or “de Morsier’s syndrome.” More recent studies have suggested these associations are independent of one another. This review provides an assessment of the historical and recent evidence linking neuroradiologic, endocrinologic and developmental morbidity in patients with ONH. The prenatal risk factors, heritability, and genetic mutations associated with ONH are described. Results: Recognition of the critical association of ONH with hypopituitarism should be attributed to William Hoyt, not Georges de Morsier. De Morsier never described a case of ONH or recognized its association with hypopituitarism or missing septum pellucidum. Hypopituitarism is caused by hypothalamic dysfunction. This, and other more recently identified associations with ONH, such as developmental delay and autism, are independent of septum pellucidum development. Other common neuroradiographic associations such as corpus callosum hypoplasia, gyrus dysplasia, and cortical heterotopia may have prognostic significance. The predominant prenatal risk factors for ONH are primiparity and young maternal age. Presumed risk factors such as prenatal exposure to drugs and alcohol are not supported by scrutiny of the literature. Heritability and identified gene mutations in cases of ONH are rare. Conclusion: Children with ONH require monitoring for many systemic, developmental, and even life-threatening problems independent of the severity of ONH and presence of brain malformations including abnormalities of the septum pellucidum. “Septo-optic dysplasia” and “de Morsier’s syndrome” are historically inaccurate and clinically misleading terms.

The vertebrate basic helix-loop-helix (bHLH) transcription factor ATOH7 (Math5) is specifically expressed in the embryonic neural retina and is required for the genesis of retinal ganglion cells (RGCs) and optic nerves. In Atoh7 mutant mice, the absence of trophic factors secreted by RGCs prevents the development of the intrinsic retinal vasculature and the regression of fetal blood vessels, causing persistent hyperplasia of the primary vitreous (PHPV). We therefore screened patients with hereditary PHPV, as well as bilateral optic nerve aplasia (ONA) or hypoplasia (ONH), for mutations in ATOH7. We identified a homozygous ATOH7 mutation (N46H) in a large family with an autosomal recessive PHPV disease trait linked to 10q21, and a heterozygous variant (R65G, p.Arg65Gly) in one of five sporadic ONA patients. High-density single-nucleotide polymorphism analysis also revealed a CNTN4 duplication and an OTX2 deletion in the ONA cohort. Functional analysis of ATOH7 bHLH domain substitutions, by electrophoretic mobility shift and luciferase cotransfection assays, revealed that the N46H variant cannot bind DNA or activate transcription, consistent with structural modeling. The N46H variant also failed to rescue RGC development in mouse Atoh7-/- retinal explants. The R65G variant retains all of these activities, similar to wild-type human ATOH7. Our results strongly suggest that autosomal recessive persistent hyperplastic primary vitreous is caused by N46H and is etiologically related to nonsyndromic congenital retinal nonattachment. The R65G allele, however, cannot explain the ONA phenotype. Our study firmly establishes ATOH7 as a retinal disease gene and provides a functional basis to analyze new coding variants.

To determine the age- and race-specific prevalence of amblyopia in Asian and non-Hispanic white children aged 30 to 72 months and of strabismus in children aged 6 to 72 months.Cross-sectional survey.A population-based, multiethnic sample of children aged 6 to 72 months was identified in Los Angeles and Riverside counties in California to evaluate the prevalence of ocular conditions.A comprehensive eye examination and in-clinic interview were conducted with 80% of eligible children. The examination included evaluation of ocular alignment, refractive error, and ocular structures in children aged 6 to 72 months, as well as a determination of optotype visual acuity (VA) in children aged 30 to 72 months.The proportion of 6- to 72-month-old participants with strabismus and 30- to 72-month-olds with optotype VA deficits and amblyopia risk factors consistent with study definitions of amblyopia.Strabismus was found in 3.55% (95% confidence interval [CI], 2.68-4.60) of Asian children and 3.24% (95% CI, 2.40-4.26) of non-Hispanic white children, with a higher prevalence with each subsequent older age category from 6 to 72 months in both racial/ethnic groups (P=0.0003 and 0.02, respectively). Amblyopia was detected in 1.81% (95% CI, 1.06-2.89) of Asian and non-Hispanic white children; the prevalence of amblyopia was higher for each subsequent older age category among non-Hispanic white children (P=0.01) but showed no significant trend among Asian children (P=0.30).The prevalence of strabismus was similar in Asian and non-Hispanic white children and was found to be higher among older children from 6 to 72 months. The prevalence of amblyopia was the same in Asian and non-Hispanic white children; prevalence seemed to be higher among older non-Hispanic white children but was relatively stable by age in Asian children. These findings may help clinicians to better understand the patterns of strabismus and amblyopia and potentially inform planning for preschool vision screening programs.The author(s) have no proprietary or commercial interest in any materials discussed in this article.

To determine the prevalence and causes of decreased visual acuity (VA).Population-based cross-sectional study.Multi-ethnic sample of children 30 to 72 months of age identified in Los Angeles.All eligible children underwent a comprehensive ophthalmic evaluation including monocular VA testing, cover testing, cycloplegic autorefraction, fundus evaluation, and VA retesting with refractive correction. Decreased VA was defined as presenting or best-measured VA worse than 20/50 in children 30 to 47 months of age and worse than 20/40 for children 48 months of age and older. The prevalence and causes of decreased VA were determined, for both presenting and best-measured VA, in the better-seeing and the worse-seeing eyes.Prevalence and causes of decreased vision.Presenting VA was assessed in 1840 children and best-measured VA was assessed in 1886 children. Presenting VA was decreased in the worse eye of 4.2% of Asian children and of 3.6% of non-Hispanic white (NHW) children. Close to one-fourth of these cases had no identifiable cause, and 81% of these resolved on retesting. Decreased presenting VA in the worse eye with an identifiable ophthalmic cause was present in 3.4% of Asian children and in 2.6% of NHW children. Decreased presenting VA attributable to simple refractive error (myopia ≥ 0.5 diopters [D]; hyperopia ≥ 3.0 D; astigmatism ≥ 2.0 D or ≥ 1.5 D for children older than 36 months) was present in the worse eye of 2.3% of Asian children and of 1.4% of NHW children and in the better eye of 0.5% of Asian children and of 0.3% of NHW children. Decreased best-measured VA attributable to a cause was present in the worse eye of 1.2% of both Asian children and NHW children and in the better eye of 0.2% of Asian and of 0.3% of NHW children. Amblyopia related to refractive error was the most common cause, and was 10 times as common as ocular disease. Severe visual impairment was rare.Seventy percent of all decreased VA in Asian and NHW preschool children and more than 90% of decreased VA with an identifiable cause is related to refractive error--either uncorrected refractive error or amblyopia resulting from refractive error.The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Objective: Children with congenital esotropia, amblyopia, or early visual deprivation have persistent asymmetric monocular pursuit, as measured by optokinetic nystagmus (OKN), and favor targets moving in a temporal to nasal direction. Previous studies suggest that binocular visual development is necessary for the development of symmetric monocular OKN. We recently treated patients with congenital esotropia with unconventionally early surgery to establish good binocularity. We wished to determine if mature symmetric OKN responses could develop in patients with congenital esotropia following the acquisition of good stereopsis. Methods: Electro-oculographic recordings documented horizontal eye movements in response to an electronic OKN stimulus. Patients: The recordings of three patients with congenital esotropia that had been surgically aligned before age 20 weeks and who had achieved high-grade stereopsis with random dot and Titmus stereographic testing were studied. We compared this group of children with groups of age-matched controls, including the following: (1) three patients with congenital esotropia who underwent surgical alignment after age 6 months and who had no amblyopia but poor stereopsis; (2) three children with accommodative esotropia, good ocular alignment when wearing spectacles, and good stereopsis; and (3) three normal children. Results: The normal children and those with accommodative esotropia demonstrated normal symmetrical OKN. The patients with congenital esotropia showed poor nasal to temporal OKN regardless of the degree of stereopsis or timing of surgery. Conclusions: Our results indicate that good binocularity, as measured by stereopsis, is not sufficient for the development of symmetric OKN in patients with congenital esotropia.

Background/Aims: The majority of children with optic nerve hypoplasia (ONH) develop hypopituitarism and many also become obese. These associated conditions are a major cause of morbidity and are possibly due to hypothalamic dysfunction. Because mild hyperprolactinemia often occurs in subjects with disorders of the hypothalamus, we examined whether hyperprolactinemia was present in children with ONH during the first 3 years of life and whether it was a marker for hypopituitarism and/or obesity. Methods: Data were retrospectively analyzed from a registry study of children with ONH. The initial serum prolactin was obtained prior to age 36 months (n = 125) and compared with pituitary function and body mass index at age 5. Results: 72% of subjects had an elevated initial serum prolactin and 60% had hypopituitarism. An elevated initial prolactin was associated with hypopituitarism (OR 2.58; 95% CI 1.16, 5.73), specifically with growth hormone deficiency (OR 2.77; 95% CI 1.21, 6.34). 31% of subjects had a body mass index ≥85th percentile, but this did not correlate with initial hyperprolactinemia. Conclusions: Early hyperprolactinemia correlates with the presence of hypopituitarism in children with ONH, but it is not a reliable prognosticator of hypopituitarism. Additionally, hyperprolactinemia does not predict future weight excess.

Optic nerve hypoplasia (ONH), a congenital malformation characterized by an underdeveloped optic nerve, is a seemingly epidemic cause of childhood blindness and visual impairment with associated lifelong morbidity. Although the prenatal determinants of ONH are unknown, early case reports have led to a longstanding speculation that risky health behaviors (e.g., prenatal use of recreational drugs, alcohol) are a likely culprit. There has yet to be a systematic review of the epidemiology of ONH to assess the common prenatal features that may help focus research efforts in the identification of likely prenatal correlates. A review of the past 50 years of epidemiologic research was conducted to examine the prenatal features linked with ONH and provide direction for future research. There are select prominent prenatal features associated with ONH: young maternal age and primiparity. Commonly implicated prenatal exposures (recreational or pharmaceutical drugs, viral infection, etc.) were rare or uncommon in large cohort studies of ONH and therefore unlikely to be major contributors to ONH. Familial cases and gene mutations are rare. The preponderance of young mothers and primiparity among cases of ONH is striking, although the significance is unclear. Recent research suggests a potential role for prenatal nutrition, weight gain, and factors of deprivation. With the rapidly increasing prevalence of ONH, future research should focus on investigating the relevance of young maternal age and primiparity and exploring the recently suggested etiologic correlates in epidemic clusters of ONH.

Evaluation of neurocognitive outcomes after a treatment strategy of chemotherapy followed by reduced-dose and volume irradiation for primary central nervous system (CNS) germinoma.Neuropsychological evaluations including measures of verbal and nonverbal intellectual functioning, working memory, processing speed, verbal and nonverbal memory, executive functioning, depression, anxiety, and social functioning were analyzed for all patients (N = 20) with histologically diagnosed CNS germinoma diagnosed at our institution between 2003 and 2009. All 20 patients underwent at least one neuropsychological evaluation, 14 patients had at least two evaluations, 7 patients had at least three, and 2 had four, generating a total of 43 test batteries at a mean of 3.0 years from diagnosis.The 20 patients performed as a group in the average range on all neurocognitive measures administered when compared to the nonmedical normative group. No decline over time was indicated on any of the neurocognitive measures. An improvement over time was indicated for nonverbal reasoning, nonverbal memory, processing speed, working memory, response inhibition, and cognitive flexibility. No significant differences were found by tumor location, age at diagnosis, or hydrocephalus at presentation.For pediatric and adolescent patients with newly diagnosed CNS germinoma, modest chemotherapy followed by reduced dose ventricular field irradiation with simultaneous integrated boost to the primary site, is associated with preservation of neurocognitive, social and emotional functioning.

Background Children with optic nerve hypoplasia (ONH) are at high risk for early-onset congenital central hypothyroidism (CH); however, reports of evolving, late-onset CH are rare and poorly documented. Aim To examine the clinical and biochemical data of children with ONH who developed CH after documented normal thyroid function tests at an earlier age. Patients and methods Children who developed late-onset CH were selected for review from an observational study (n = 214) that examined clinical risk factors for endocrinological abnormalities in children with ONH. Results Eight patients with ONH developed CH between the ages of 20-51 months. One child at age 28 months developed CH within 4 months of prior normal thyroid function tests. There were no associations among clinical, neuroradiographical, vision, and/or pituitary outcomes. Conclusions Children with ONH may develop CH over time, and surveillance thyroid function tests may be necessary as frequently as every four months.

In optic nerve hypoplasia (ONH), the extent of functional loss of retinal ganglion cells cannot be determined by ophthalmoscopic examination. The prognostic value of visual electrodiagnostic tests in infants and toddlers with ONH was assessed by comparison with visual outcome.85 participants with ONH had electroretinogram (ERG) and visual-evoked potential (VEP) testing to flash and to pattern-reversal checks and ocular fundus photography prior to 36 months of age. These initial measures were compared with visual acuity outcomes at 5 years of age in the better-seeing eye.Visual outcomes ranged from normal to no light perception. Electrodiagnostic tests with prognostic value were: the amplitude of the flash VEP (Spearman's rank correlations, p0.001), the threshold category of stimulus (flash or check size) that elicited a VEP (p0.001) and the amplitude of the N95 component of the pattern ERG (PERG) to 4-degree checks (p0.02). Optic nerve size and co-existing pallor were also significant correlates. Stepwise regression analysis composed a best prediction model from VEP threshold category, optic nerve size and optic disc pallor (R(2)=58%; p0.001).Optic disc diameter, observation of disc pallor, VEP and PERG testing in infancy are useful for establishing the visual prognosis at 5 years of age in children with ONH. This is consistent with the notion that these parameters are related to the anatomic and functional preservation of retinal ganglion cells.

The diagnosis and management of amblyopia, strabismus, refractive error, and other vision disorders in children are dependent upon an accurate and reliable determination of visual acuity (VA). VA is also the most common measure used in vision screening to identify children who may require comprehensive eye examinations. While VA of 20/20 or better is widely considered to be “normal” for most adult patients,1 VA worse than 20/20 is common in preschool children, even in the absence of refractive error or other vision disorders.2 For this reason, vision screening referral criteria and definitions of amblyopia are often based on acuity values in the range of 20/30 to 20/50 or worse. However, there are no published VA norms derived from population-based samples of preschool children. Thus, it remains imperative to define normal VA test performance in healthy preschool children, including its dependence on age. The Amblyopia Treatment Study (ATS) HOTV visual acuity testing protocol was specifically developed for young children. It is currently used by the pediatric vision research community and increasingly used in clinical practice by pediatric eye care providers. Testability rates are high for preschool children3,4 and measurements can sometimes be obtained in children as young as 2 years of age.5,6 As is the case for other optotype acuity tests, existing studies of HOTV protocols in young children are not population-based,7 and/or do not report data for normal children (i.e., children without visually significant refractive error or ocular abnormalities).4,8,9,10 The Multi-Ethnic Pediatric Eye Disease Study (MEPEDS) is an ongoing cross-sectional, population-based study, with the specific aims of providing prevalence estimates for amblyopia, strabismus, and refractive error in a multi-ethnic cohort of children between the ages of 6 and 72 months. The purpose of this report is to provide population-based, age-specific visual acuity normative data for monocular VA and interocular VA differences in African-American and Hispanic children between the ages of 30 and 72 months who have no significant refractive error or other ophthalmic abnormalities.

Purpose: The purpose of this study is to describe and clarify the birth and prenatal characteristics of a large cohort of children with optic nerve hypoplasia. Methods: This is a descriptive report of 204 patients aged £ 36 months and enrolled in a prospective study at the Children’s Hospital Los Angeles. Birth characteristics, including complications, were abstracted from study files and medical records. Systematic maternal interviews were conducted to obtain detailed prenatal histories. National birth data were used for comparison with birth findings. Results: Birth characteristics were unremarkable for birthweight and gestation, but significant for increased frequency of caesarean delivery and fetal and neonatal complications. Young maternal age and primaparity were dominating maternal features. Preterm labour, gestational vaginal bleeding, low maternal weight gain and weight loss during pregnancy were prevalent. Conclusions: These findings confirm young maternal age and primaparity as associated risk factors, challenge many other suggested factors such as alcohol and drug abuse, and introduce potentially significant prenatal characteristics such as maternal weight loss and early gestational vaginal bleeding as aetiological correlates.

Optic nerve hypoplasia (ONH) has a wide clinical spectrum. When it is associated with absence of the septum pellucidum, it has been termed septo-optic dysplasia. Over the past 50 years, much has been learned about ONH and its association with pituitary endocrinopathies. Causative factors have been sought that may disrupt development of the optic nerve and the hypothalamic-pituitary axis simultaneously. The endocrinological aspects of ONH require lifelong monitoring and replacement of pituitary hormones when necessary. Children with ONH are also at greater risk for structural abnormalities of the brain, and abnormalities in certain structures are positively correlated with increased risk for pituitary deficiencies. However, it has also been shown that children with ONH and "normal" head imaging can still manifest endocrinopathies. Subsequently, a long-term multidisciplinary approach, involving pediatric specialists in ophthalmology, endocrinology, neurology, and behavioral therapy, is critical to optimize growth and development of all children with ONH.