Changes in the Anterior Lamina Cribrosa Morphology with Glaucoma Severity.

This study was designed to evaluate if primary open angle glaucoma (POAG) and its severity are associated with the shape of the lamina cribrosa (LC) as measured by a global shape index (LC-GSI), or other indices of LC curvature or depth. Optical coherence tomography (OCT) scans of the optic nerve head (OHN) were obtained from subjects with POAG (n = 99) and non-glaucomatous controls (n = 76). ONH structures were delineated, the anterior LC morphology reconstructed in 3D, and the LC-GSI calculated (more negative values denote greater posterior concavity). Anterior LC depth and 2D-curvature were also measured. Severity of glaucoma was defined by the extent of visual field loss, based on the Hodapp-Parrish-Anderson grading. Linear regression analyses compared LC characteristics between controls, mild-moderate, and advanced POAG groups. After adjusting for age, gender, ethnicity, intraocular pressure, axial length and corneal curvature, the LC-GSI was most negative in the advanced POAG group (mean [standard error] = -0.34 [0.05]), followed by the mild-moderate POAG group (-0.31 [0.02]) and then controls (-0.23 [0.02], PTrend = 0.01). There was also a significant trend of increasing LC depth and greater LC horizontal curvature with increasing severity of glaucoma (PTrend = 0.04 and 0.02, respectively). Therefore, with more severe glaucoma, the LC-GSI was increasingly more negative, and the anterior LC depth and curvature greater. These observations collectively correspond to greater cupping of the ONH at the level of the LC. As the LC-GSI describes the 3D anterior LC morphology, its potential usage may be complementary to existing ONH parameters measured on OCT.

Assessment of Circumferential Angle Closure with Swept-Source Optical Coherence Tomography: a Community Based Study.

PURPOSE: To evaluate the diagnostic performance of swept-source optical coherence tomography (SS-OCT, CASIA SS-1000; Tomey Corporation, Nagoya, Japan) for angle closure detection, in comparison with gonioscopy, in a community setting. DESIGN: Reliability analysis. METHODS: A total of 2027 phakic subjects aged ≥50 years, with no previous history of glaucoma, laser (including peripheral iridotomy), intraocular surgery, or ocular trauma, were consecutively recruited from a community polyclinic in Singapore. Gonioscopy was performed by a single trained ophthalmologist. SS-OCT angle scans, which obtain radial scans for the entire circumference of the angle, were analyzed by a single examiner, masked to the subject's clinical details. On SS-OCT images, angle closure was defined as contact between the iris and any part of the angle wall anterior to the scleral spur. Different cutoff values of the degree of circumferential angle closure (≥35%, ≥50%, and ≥75%) were taken for analysis to assess SS-OCT performance in detecting angle closure. RESULTS: A total of 1857 subjects (91.6%) were included in the final analysis after excluding poor-quality SS-OCT scans. Almost 90% of the subjects were Chinese, with a mean age of 61.8 ± 6.7 years, and more than half were women (63.5%). The overall AUC of SS-OCT manual grading against gonioscopy was 0.84 (95% confidence interval, 0.81-0.88). The prevalence of angle closure on SS-OCT was 26.1% for the ≥35% definition, with an area under the curve of 0.80 (0.77-0.84), sensitivity of 82.5% (75.3%-88.4%), and specificity of 78.5% (76.5%-80.4%). The first-order agreement coefficient statistics for the 2-quadrant gonioscopic definition of angle-closure with corresponding ≥35%, ≥50%, and ≥75% angle closure definitions for SS-OCT were good at 0.89 (0.83-0.93), 0.88 (0.842-0.93), and 0.88 (0.831-0.99), respectively. CONCLUSIONS: In this large community-based study, SS-OCT exhibited moderate performance for angle closure detection compared to gonioscopy as the reference standard.

World Association of Sleep Medicine (WASM) 2016 standards for recording and scoring leg movements in polysomnograms developed by a joint task force from the International and the European Restless Legs Syndrome Study Groups (IRLSSG and EURLSSG).

This report presents the results of the work by a joint task force of the International and European Restless Legs Syndrome Study Groups and World Association of Sleep Medicine that revised and updated the current standards for recording and scoring leg movements (LM) in polysomnographic recordings (PSG). First, the background of the decisions made and the explanations of the new rules are reported and then specific standard rules are presented for recording, detecting, scoring and reporting LM activity in PSG. Each standard rule has been classified with a level of evidence. At the end of the paper, Appendix 1 provides algorithms to aid implementation of these new standards in software tools. There are two main changes introduced by these new rules: 1) Candidate LM (CLM), are any monolateral LM 0.5-10 s long or bilateral LM 0.5-15 s long; 2) periodic LM (PLM) are now defined by runs of at least four consecutive CLM with an intermovement interval ≥10 and ≤ 90 s without any CLM preceded by an interval <10 s interrupting the PLM series. There are also new options defining CLM associated with respiratory events. The PLM rate may now first be determined for all CLM not excluding any related to respiration (providing a consistent number across studies regardless of the rules used to define association with respiration) and, subsequently, the PLM rate should also be calculated without considering the respiratory related events. Finally, special considerations for pediatric studies are provided. The expert visual scoringof LM has only been altered by the new standards to require accepting all LM > 0.5 s regardless of duration, otherwise the technician scores the LM as for the old standards. There is a new criterion for the morphology of LM that applies only to computerized LM detection to better match expert visual detection. Available automatic scoring programs will incorporate all the new rules so that the new standards should reduce technician burden for scoring PLMS.

Interrelationships between obesity, obstructive sleep apnea syndrome and cardiovascular risk in obese adolescents.

BACKGROUND/OBJECTIVES: Obstructive sleep apnea syndrome (OSAS) may be a cardiovascular disease (CVD) risk factor independently of obesity in adults. Pediatric studies have associated OSAS with endothelial dysfunction, but few studies have examined relationships between OSAS and macrovascular sequelae. Our objective was to examine OSAS's independent contribution to macrovascular CVD risk measures in obese adolescents. SUBJECTS/METHODS: This cross-sectional observational study was conducted at Children's Hospital of Philadelphia Clinical Research and Academic Sleep Centers, and University of Pennsylvania Vascular Research Unit. Thirty-one obese non-diabetic adolescents underwent anthropometric measurements, overnight polysomnography, fasting laboratory draw and cardiovascular imaging. Cardiovascular outcome measures included maximal carotid intima-media thickness (cIMTmax), a measure of carotid structural changes, and carotid-femoral pulse wave velocity (CFPWV), an aortic stiffness measure whose relationship vis-à-vis OSAS in children has not been previously examined. Carotid diameter and augmentation index (AIx, measuring central pressure augmentation from wave reflections) were assessed. Potential confounding variables examined included blood pressure, lipoproteins, high-sensitivity C-reactive protein, insulin and glucose. RESULTS: The apnea hypopnea index, a primary OSAS measure, was not associated with cIMTmax, carotid diameter, CFPWV or AIx. body mass index (BMI) associated positively with cIMTmax (r=0.52, P=0.006) and CFPWV (r=0.45, P=0.01). Mean asleep end-tidal CO2 was negatively associated with carotid diameter (r=-0.63, P<0.0005). Insulin levels were negatively associated with AIx (r=-0.53, P=0.02). CONCLUSIONS: OSAS did not predict carotid structural changes or arterial stiffness independently of BMI in obese adolescents. Higher insulin levels associated with lower central pressure wave augmentation. Finally, long-term hypercapnia may predispose to carotid narrowing.

Positional and rotational stability of the toric phakic intraocular lens under high +Gz environments.

BACKGROUND: Phakic intraocular lens (PIOL) implantation is a surgical option for correction of refractive errors. PIOLs can be use to correct myopia, hyperopia, and astigmatism. It is a surgical option available to patients in addition to methods such as laser cornea refractive surgery, e.g., laser assisted in-situ keratomileusis (LASIK) and photo-refractive keratectomy (PRK). Visian implantable collamer lens (ICL) are posterior chamber lenses which are surgically positioned in a phakic eye in the sulcus between the iris diaphragm and the natural crystalline lens. CASE REPORT: This case report describes the stability of Visian toric ICL in a candidate with bilateral implants under high +Gz force exposure in a human centrifuge trainer. The subject was sequentially exposed to three incremental +Gz profiles of +5 Gz, +7 Gz, and +9 Gz. Pre- and post-+Gz exposure, ophthalmic examination revealed no ICL displacement, implant touch or induced cataract, or change in refractive error. DISCUSSION: The rotational stability of the toric implants was also demonstrated by identical subjective refractions in both eyes taken pre- and post-+Gz, exposure. A search of the literature did not reveal any published articles on intraocular stability of ICL in the +Gz environment. This case report suggests that ICL may be considered an alternative to laser refractive surgery for patients subjected to a high +G, environment such as military aviators.

Congenital central hypoventilation syndrome in children.

Congenital central hypoventilation syndrome (CCHS) is a rare, lifelong condition wherein control of breathing is abnormal and patients present with symptoms of alveolar hypoventilation. The severity of hypoventilation varies and although most patients present in the neonatal period, late onset cases have been reported. In 2003, it was discovered that mutations in the PHOX2B gene were responsible for CCHS. This gene also plays a role in neural crest cell migration, and many patients present with symptoms of autonomic dysfunction in addition to hypoventilation. The pathophysiology responsible for hypoventilation remains unclear although a unifying hypothesis is that the abnormality is located in areas of the brain involved in integration of chemoreceptor afferent pathways for ventilation. The goal of treatment for CCHS is to ensure adequate ventilation during wakefulness and sleep. A variety of ventilation modalities are available including positive pressure ventilation via tracheostomy, non-invasive ventilation via nasal mask, and diaphragmatic pacing. With close monitoring and support, children with CCHS can be expected to function well in society and have a good quality of life.

Heart rate chaos in obstructive sleep apnea in children.

Obstructive sleep apnea syndrome (OSAS) in children is associated with a bradytachyarrhythmia during an obstructive event. Polysomnographic recordings were obtained from 15 children; 9 had OSAS (apnea/hypopnea index = 13.6 +/- 8.2/hr, mean +/- SD) and 6 normal controls. Heart rate variability was analyzed for the presence of chaotic dynamics. Using a 5-minute sliding window, chaos was detected using numerical titration technique. In both groups, REM had a higher chaotic intensity than NREM sleep (p < 0.05). Furthermore, chaos was significantly increased during periods with apneic events compared to stable breathing. These data indicate that sleep state and disordered breathing are important determinants of the autonomic control of heart rate chaos in children.

Respiratory flutter syndrome: an underrecognized cause of respiratory failure in neonates.

We report the clinical and respiratory data of three neonates with flutter of the diaphragm and intercostal muscles, presenting soon after birth with respiratory failure. The breathing pattern was dirhythmic with superimposed frequencies, one regular and slow (60/min) representing the underlying respiratory rate, the other fast (> 300/min) and limited to inspiration. Nasal continuous positive airway pressure immediately normalized the breathing pattern in one infant, and improved ventilation in the two others. Pharmacologic therapy with chlorpromazine terminated the respiratory flutter and permitted weaning of ventilatory support within a few hours. Coexistent dysphagia suggested a disorder of brainstem function, although the children were otherwise developmentally normal at 8, 10, and 26 mo old. Laryngomalacia and gastroesophageal reflux were also present. We propose that the occurrence of respiratory flutter, dysphagia, laryngomalacia, and gastroesophageal reflux in a neonate constitutes a distinct clinical entity, termed the "respiratory flutter syndrome." The diagnosis of three infants with this presentation during an 18-mo period suggests that this may be a more frequent cause of respiratory failure in newborns than previously recognized.

Skeletal dysplasias and their effect on the respiratory system.

Children with skeletal dysplasia frequently have pulmonary disease which can be life threatening. These pulmonary problems are due to multiple aetiologies including thoracic and craniofacial anomalies predisposing to restrictive lung disease, upper airway obstruction and central apnoea. Recognition of pulmonary disease and early intervention improves the survival and quality of life for these children.

Treatment of sleep-disordered breathing in children with myelomeningocele.

The prevalence of moderate to severe sleep-disordered breathing (SDB) in patients with myelomeningocele may be as high as 20%, but little information is available regarding treatment of these patients. To assess the efficacy and complications of treatments for these children, we collected data on 73 patients from seven pediatric sleep laboratories. Obstructive sleep apnea (OSA, n = 30) and central apnea (n = 25) occurred more frequently than central hypoventilation (n = 12). We also describe a sleep-exacerbated restrictive lung disease type of SDB in 6 patients who had hypoxemia during sleep without apnea or central hypoventilation. For each type of SDB, effective treatments were identified in a stepwise process, moving towards more complex and invasive therapies. For OSA, adenotonsillectomy was often ineffective (10/14), whereas nasal continuous positive airway pressure (CPAP) was usually successful (18/21). For central apnea, methylxanthines and/or supplemental oxygen proved sufficient in 2 of 9 and 3 of 6, respectively, but noninvasive positive pressure ventilation was required in 7 children. For central hypoventilation, supplemental oxygen (alone or with methylxanthines), noninvasive positive pressure ventilation, and tracheostomy with positive pressure ventilation were effective in 3, 2, and 2 patients, respectively. Sleep-exacerbated restrictive lung disease always required supplemental oxygen treatment, but in 2 cases also required noninvasive positive pressure ventilation; nutritional and orthopedic procedures also were helpful. Posterior fossa decompression was used for the first three types of SDB, but data were insufficient to delineate specific recommendations for or against its use. In summary, evaluation by an experienced, multidisciplinary team can establish an effective treatment regime for a child with myelomeningocele and SDB.

Sleep architecture and respiratory disturbances in children with obstructive sleep apnea.

Little is known regarding sleep architecture in children with the obstructive sleep apnea syndrome (OSAS). We hypothesized that sleep architecture was normal, and that apnea increased over the course of the night, in children with OSAS. We analyzed polysomnographic studies from 20 children with OSAS and 10 control subjects. Sleep architecture was similar between the groups. Of obstructive apneas 55% occurred during rapid eye movement (REM) sleep. The apnea index, apnea duration, and degree of desaturation were greater during REM than non-REM sleep. OSAS data from the first and third periods of the night (periods A and C) were compared. Both the overall and the REM apnea index increased between periods A and C (11 to 25/h, p < 0.02; and 24 to 51/h, p < 0.01, respectively). There was no difference in Sa(O(2)) over time. Spontaneous arousals, but not respiratory-related arousals, were more frequent during non-REM than REM sleep; these did not change from periods A to C. We conclude that children with OSAS have normal sleep stage distribution. OSAS is predominantly a REM phenomenon in children. Obstructive apnea worsens over the course of the night, independent of the changing amounts of REM sleep. We speculate that this increase in apnea severity may be secondary to upper airway muscle fatigue, changes in upper airway neuromotor control, or changes in REM density.

Obstructive sleep apnea syndrome: differences between children and adults.

The obstructive sleep apnea syndrome is a common cause of morbidity in childhood. The clinical presentation, pathophysiology, polysomnographic characteristics and treatment differ between children and adults. Measurements of the upper airway pressure-flow characteristics can be useful in evaluating upper airway function in patients with OSAS as well as the normal population.

Sleep-disordered breathing in children.

Sleep-disordered breathing, particularly the obstructive sleep apnea syndrome, is common during childhood. Complications include neurocognitive deficits, growth failure, and pulmonary hypertension. Nevertheless, sleep-disordered breathing is often unrecognized in children. New syndromes, such as the upper airway resistance syndrome, have recently been described. Polysomnography is invaluable for the evaluation of sleep-disordered breathing. Advances in diagnosis and management can alleviate much of the morbidity previously associated with sleep-related respiratory disorders.

Pathophysiology of childhood obstructive sleep apnea: current concepts.

The obstructive sleep apnea syndrome (OSAS) is a common and serious condition during childhood. Its pathophysiology remains poorly understood. Although OSAS is related to adenotonsillar hypertrophy in children, adenotonsillar hypertrophy is not likely the sole cause of sleep-disordered breathing in this age group. Rather, large tonsils and adenoids appear to precipitate OSAS in children with underlying abnormalities of upper airway function. Normal children have a relatively narrow upper airway, but maintain airway patency during sleep because of increased upper airway neuromotor tone and an increased central ventilatory drive. We speculate that OSAS occurs in those children lacking the compensatory upper airway neuromotor responses.

Late-onset central hypoventilation with hypothalamic dysfunction: a distinct clinical syndrome.

Idiopathic central hypoventilation has occasionally been reported in previously well children after infancy. The relationship between this late-onset central hypoventilation syndrome (LO-CHS) and congenital central hypoventilation syndrome (CCHS) has not been established. Both CCHS and LO-CHS have been associated with neural crest tumors, such as ganglioneuroblastoma and ganglioneuroma, and they generally occur in the presence of a histologically normal central nervous system. At least 10 case reports of idiopathic LO-CHS featured evidence of hypothalamic dysfunction (HD), including hyperphagia, hypersomnolence, thermal dysregulation, emotional lability, and endocrinopathies. We report on a case of LO-CHS/HD successfully treated by nasal intermittent positive pressure ventilation (NIPPV). Despite the commonalties with CCHS, we propose that LO-CHS/HD is a distinct clinical syndrome. In addition to the markedly different age at presentation, features of hypothalamic dysfunction are not seen in CCHS. Review of the literature was undertaken to further clarify the full spectrum of the disease.

Response to inspiratory resistive loading during sleep in normal children and children with obstructive apnea.

The response to inspiratory resistance loading (IRL) of the upper airway during sleep in children is not known. We, therefore, evaluated the arousal responses to IRL during sleep in children with the obstructive sleep apnea syndrome (OSAS) compared with controls. Children with OSAS aroused at a higher load than did controls (23 +/- 8 vs. 15 +/- 7 cmH(2)O. l(-1). s; P < 0.05). Patients with OSAS had higher arousal thresholds during rapid eye movement (REM) vs. non-REM sleep (P < 0.001), whereas normal subjects had lower arousal thresholds during REM (P < 0.005). Ventilatory responses to IRL were evaluated in the controls. There was a marked decrease in tidal volume both immediately (56 +/- 17% of baseline at an IRL of 15 cmH(2)O. l(-1). min; P < 0.001) and after 3 min of IRL (67 +/- 23%, P < 0.005). The duty cycle increased. We conclude that children with OSAS have impaired arousal responses to IRL. Despite compensatory changes in respiratory timing, normal children have a decrease in minute ventilation in response to IRL during sleep. However, arousal occurs before gas-exchange abnormalities.

Significance of isolated bradycardia detected by home monitoring.

OBJECTIVE: To determine the cause of isolated bradycardia during home cardiorespiratory monitoring. SETTING: A tertiary care hospital. STUDY DESIGN: A retrospective review of the charts of 8 patients with severe isolated bradycardia on their home monitoring reports. All subjects underwent polysomnography including a pH probe. RESULTS: Monitor reports showed a characteristic pattern of long (30 to 60 seconds) periods of bradycardia, sometimes with asystole, associated with irregular respiratory efforts. All patients had severe gastroesophageal reflux, with a pH <4 for 63% +/- 22% (mean +/- SD) of recording time. No patient had other abnormalities to explain the bradycardia. Bradycardia resolved after successful treatment of reflux. CONCLUSION: A pattern of isolated bradycardia associated with irregular respiratory efforts on home monitoring is highly suggestive of gastroesophageal reflux and should prompt further evaluation and treatment.