Prenatal features of ductus arteriosus-related branch pulmonary stenosis in fetal pulmonary atresia.

OBJECTIVE: Ductus arteriosus (DA)-related branch pulmonary stenosis (PS), due to ductal tissue migration into the proximal pulmonary artery (PA) ipsilateral to the DA, is common in newborns with pulmonary atresia (PAtr) and contributes significantly to their mortality and morbidity. We sought to define fetal echocardiographic predictors of DA-PS in PAtr. METHODS: This was a study of all neonates diagnosed prenatally with PAtr and a DA-dependent pulmonary circulation, with a DA that joined the underbelly of the arch, who had undergone surgical or catheter intervention in our hospital between 2009 and 2018. The postnatal echocardiograms and clinical records were reviewed to confirm the presence or absence of DA-PS based on the need for angioplasty at initial intervention and/or development of proximal PA stenosis post intervention. Fetal echocardiograms were examined for the features of DA-PS. RESULTS: Of 53 fetuses with PAtr, 34 (64%) had analyzable images, including 20/34 (59%) with and 14/34 (41%) without DA-PS. An inability to visualize the branch PAs in the same plane, largely associated with abnormal DA insertion into the ipsilateral PA (85% of cases), had sensitivity, specificity and positive (PPV) and negative (NPV) predictive values of 75%, 100%, 100% and 74%, respectively, for the prediction of postnatal DA-PS. The mean branch PA posterior bifurcation angle was more obtuse in cases with DA-PS compared to cases without DA-PS (117° ± 17° vs 79° ± 17°, P < 0.001), and an angle of > 100°, the preoperative cut-off observed previously in affected newborns, had a sensitivity, specificity, PPV and NPV of 88%, 79%, 82% and 85%, respectively. The receiver-operating-characteristics curve revealed an angle of ≥ 105° to have a sensitivity and specificity of 88% and 93%, respectively, for prenatal prediction of DA-PS. The presence of one or both features (inability to image in the same plane and the posterior bifurcation angle of ≥ 105°) had a sensitivity, specificity, PPV and NPV of 100%, 93%, 95% and 100%, respectively. CONCLUSION: An inability to visualize the branch PAs in the same plane, associated with abnormal insertion of the DA in most cases, and/or the presence of a posterior PA bifurcation angle of ≥ 105° are predictive features of postnatal DA-PS in fetuses with PAtr. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.

Population trends in prenatal detection of transposition of great arteries: impact of obstetric screening ultrasound guidelines.

OBJECTIVES: Dextro-transposition of the great arteries (d-TGA) is one of the most common critical neonatal heart defects, with a low detection rate antenatally. We sought to evaluate trends in the prenatal detection of d-TGA with or without ventricular septal defect (VSD) in Alberta over the past 13 years, examining the potential impact of ultrasound guidelines incorporating screening of cardiac outflow tracts, updated in 2009-2010 and in 2013, and factors affecting detection of the condition. METHODS: All fetuses and neonates with d-TGA, with or without VSD, encountered between 2003 and 2015 in the province of Alberta, were identified retrospectively. Clinical records including obstetric ultrasound reports were reviewed. Pregnancy outcome, common referral indications and associated maternal and fetal pathology in affected pregnancies were assessed. RESULTS: From 2003 to 2015, 127 cases with d-TGA were encountered in Alberta, of which 47 (37%) were detected prenatally. Prenatal detection improved over the study period, from 14% in 2003-2010, to 50% in 2011-2013, and to 77% in 2014-2015. Of the 47 fetuses with a prenatal diagnosis of d-TGA, an indication for fetal echocardiography included abnormal or poorly visualized cardiac outflows with normal four-chamber view in 46 (98%). Comorbidities were identified in 12 mothers, only five of which represented an additional reason for fetal echocardiography referral, and four fetuses had extracardiac pathology. CONCLUSION: Substantial improvement in the prenatal detection of d-TGA has been observed in Alberta over the past few years, owing to improved screening of cardiac outflow tracts on routine obstetric ultrasound examination in otherwise healthy pregnancies, and has been temporally associated with updated obstetric ultrasound guidelines suggesting that these contributed to optimized screening of affected pregnancies. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Scanning laser polarimetry in a selected group of patients with glaucoma and normal controls.

PURPOSE: To evaluate the ability of scanning laser polarimetry to discriminate between subjects with glaucoma with specific patterns of visual field defect and normal controls. METHODS: This cross-sectional, prospective study in a glaucoma practice, focused on subjects with glaucoma with predefined types of visual field defect, including advanced (group A, n = 14), localized (group L, n = 46), or mixed (diffuse and localized) defects (group M, n = 22) and normal controls (n = 32). Scanning laser polarimetry was performed in one study eye per subject. Two methods of analysis were used: a subjective analysis, in which examination printouts with the image of the optic disk manually blocked were classified by two observers masked to the diagnosis, and a logistic regression analysis of the retardation parameters included in the printouts. RESULTS: The observers correctly identified 97% of the controls and 68% of subjects with glaucoma (overall correct classification of 77%), with 93%, 70%, and 47% of patients from groups A, L, and M, respectively, being correctly identified. The best discrimination obtained with the logistic regression correctly identified 69% of controls and 94% of glaucoma subjects (overall correct classification of 87%). The performance was only slightly better for cases from group A compared with L and M. CONCLUSIONS: Subjective assessment of the scanning laser polarimetry standard printout of single eyes might not be sensitive enough to detect cases of glaucoma with localized or milder mixed types of visual field defect. The discriminating ability of scanning laser polarimetry improves slightly when logistic regression analysis is employed.

Prevalence of split nerve fiber layer bundles in healthy eyes imaged with scanning laser polarimetry.

PURPOSE: The GDx (Laser Diagnostic Technologies, San Diego, CA) is a scanning laser polarimeter designed to assess the peripapillary nerve fiber layer in vivo. On the GDx, a nerve fiber bundle can appear as a single or as a split bundle. The aim of our study was to determine the prevalence of split nerve fiber layer bundles and to demonstrate their clinical relevance. DESIGN: Cross-sectional study. PARTICIPANTS: Two hundred fifty-four healthy volunteers participated. METHODS: We imaged 454 eyes of 254 healthy white persons with the GDx. All eyes had intraocular pressure of 21 mmHg or less, normal appearance of the optic nerve head, and normal visual fields (Humphrey Field Analyzer 24-2 full threshold program). According to our working definition, a bundle appeared 'split' when the color-coded pixels corresponding to areas of higher retardation were clearly divided into two more-or-less symmetrical parts not resembling a wedge defect. The classification was performed by two independent observers who used an identical set of reference examples to standardize the classification. MAIN OUTCOME MEASURES: The presence of a split nerve fiber layer bundle. RESULTS: Interobserver agreement was very good (kappa = 0.83), and a consensus was reached in all cases. In 419 eyes (92.3%) there was no split bundle. A split superior bundle was seen in 29 eyes (6.4%). A split inferior bundle was observed in five eyes (1.1%), and in one eye (0.2%) a split bundle was seen superiorly and inferiorly. When considering subjects, a split superior bundle (either in the right eye, or in the left eye, or in both eyes) occurred in 12.0% of normal subjects. The 'superior maximum' parameter was significantly lower in eyes with a split superior bundle than in eyes with a single superior bundle (67.2 microm vs. 89.9 microm; P<0.001). The same was observed for the 'symmetry' parameter (0.88 microm vs. 0.98 microm; P<0.001). CONCLUSIONS: Split nerve fiber layer bundles are a common finding in healthy eyes when imaged with the GDx. A split superior bundle is the most frequent variation, in which cases an abnormal superior maximum or symmetry parameter, otherwise potential indicators of glaucoma, should not readily be interpreted as abnormal.

Axonal loss in a patient with anterior ischemic optic neuropathy as measured with scanning laser polarimetry.

PURPOSE: To report Nerve Fiber Analyzer (NFA/GDx; Laser Diagnostic Technologies, San Diego, California) measurements in a patient during the early phase of an anterior ischemic optic neuropathy. METHODS: Case report. A 58-year old man with acute anterior ischemic optic neuropathy had repeated NFA/GDx scans of the nerve fiber layer adjacent to the optic nerve head of the involved eye, as well as repeated HFA 30.2 (Humphrey Field Analyzer; Humphrey Systems, San Leandro, California) visual field examinations. RESULTS: At presentation (day 0), he had a normal superior nerve fiber bundle on the NFA/GDx, with a deep inferior hemifield scotoma. By day 21 and day 36, the superior nerve fiber bundle thinned on the NFA/GDx, whereas the scotoma remained practically unchanged. CONCLUSION: These findings suggest that after the onset of an anterior ischemic optic neuropathy, acute loss of axonal function results in scotoma, presumably from ischemia. This is followed by a gradual disappearance of nerve fiber tissue, as measured with the NFA/GDx, within several weeks.

Comparison of artificial eye amplitudes with acrylic and hydroxyapatite spherical enucleation implants.

PURPOSE: To compare artificial eye amplitudes in patients who randomly received either a hydroxyapatite or an acrylic, scleral-covered spherical implant after enucleation. DESIGN: Randomized, controlled trial. PARTICIPANTS: Thirty-four consecutive patients who underwent enucleation because of an intraocular melanoma and 21 healthy control participants from the hospital staff. METHODS: Eligible patients randomly received a hydroxyapatite or an acrylic, scleral-covered spherical orbital implant. Fourteen patients were fitted with a hydroxyapatite implant, and 16 were fitted with an acrylic implant. We measured horizontal and vertical saccadic amplitudes of both the artificial eye and the healthy eye. Measurements were performed with the magnetic search coils technique. Saccadic amplitudes of the artificial eye were compared with the healthy eye of the patient. The amplitudes of the healthy eyes were compared with saccadic amplitudes of control participants. The interval from surgery to measurements was at least 3 months in all patients. Saccadic gain (artificial eye and eye amplitude divided by target amplitude) and saccadic symmetry (artificial eye amplitude divided by healthy eye amplitude) were calculated. MAIN OUTCOME MEASURES: Saccadic gain and saccadic symmetry. RESULTS: The gain in the healthy eyes of the patients was comparable with the gain of the control eyes. Saccadic symmetry was 1.0 in control participants. In patients, it was 0.334 in horizontal saccades and 0.577 in vertical saccades. However, saccadic symmetry did not differ significantly between the acrylic group and the hydroxyapatite group (P: > 0.1 for any saccadic direction). Equivalence was detectable with a power more than 90% for horizontal saccades and more than 80% for vertical saccades. Curvilinearity was rejected for both patient groups and for all saccadic directions (P: > 0.5). CONCLUSIONS: When no motility peg is placed, acrylic and hydroxyapatite spherical implants yield comparable saccadic amplitudes of the artificial eye. Artificial eye amplitudes were markedly more restricted horizontally than vertically. In all saccadic directions, the relation between target amplitude and artificial eye amplitude was linear.

Reproducibility of measurements with the nerve fiber analyzer (NfA/GDx).

PURPOSE: To determine the reproducibility of measurements with the Nerve Fiber Analyzer, a scanning laser polarimeter designed for quantifying glaucoma in healthy patients and patients with glaucoma. The authors also assessed the variance of measurements between instruments. METHODS: Measurements were made with the third generation Nerve Fiber Analyzer, the GDx. The study consisted of three parts. In the first part, the authors measured the right eyes of 10 healthy volunteers on 5 consecutive days. In the second part, 45 patients with glaucoma underwent Nerve Fiber Analyzer measurements of one randomly selected eye on two separate days in a 5-week period. For all 14 available parameters, reproducibility of measurements was expressed in terms of 95% limits of agreement and as the intraclass correlation coefficient. The Nerve Fiber Analyzer software has an option of creating a mean image from a selection of single images; for both parts of the study, the reproducibility of measurements was calculated for a "single image," and a "mean-of-three" image. In the third part of the study, 17 volunteers underwent repeated Nerve Fiber Analyzer measurement sessions on each of three different instruments. Using multivariate analysis of variance, the authors determined the variance of measurements between instruments. RESULTS: The reproducibility of measurements varied considerably across parameters. Limits of agreement in mean images for superior maximum and inferior maximum were 7.2 microm and 7.7 microm, respectively in the healthy volunteers, and 8.7 microm and 7.9 microm, respectively in the patients with glaucoma. For healthy patients, the intraclass correlation coefficient was greater than 90% in 10 of 14 parameters. In patients with glaucoma, the intraclass correlation coefficient was greater than 90% in 13 of 14 parameters. Some parameters reproduced better in a mean than in a single image; these differences, however, were small and generally not statistically significant. The between-instruments component also varied across parameters and was highest in ratio-based parameters. CONCLUSIONS: The reproducibility of measurements varied across parameters. In general, the reproducibility of measurements with the Nerve Fiber Analyzer was high. The reproducibility of measurements was similar between healthy patients and patients with glaucoma. Any measured change in nerve fiber layer thickness would be statistically significant if it exceeded approximately 7 or 8 microm in the superior maximum or inferior maximum parameter in healthy patients. Reproducibility of measurements hardly differed between single images and mean images. The reproducibility of measurements among the three instruments we used was highest for straight parameters.

Retinal nerve fiber layer thickness in human strabismic amblyopia.

BACKGROUND AND PURPOSE: Amblyopia is characterized by histopathological changes in the visual cortex and lateral geniculate nucleus. In the retina, however, no abnormalities have yet been reported. The purpose of this study was to compare the nerve fiber layer (NFL) thickness in the amblyopic eye with that in the sound eye of patients with strabismic amblyopia. As a practical implication, we investigated the validity of comparing Nerve Fiber Analyzer (NFA) measurements obtained in amblyopic eyes to the normative database built into the NFA. METHODS: NFL thickness was measured with a third generation NFA, the GDx (Laser Diagnostic Technologies, San Diego, CA). This is a scanning laser polarimeter, designed for monitoring glaucoma. The following NFL thickness parameters (all in microns) were compared: average thickness, superior maximum, inferior maximum, superior average, inferior average, nasal median and temporal median. Twenty patients with strabismic amblyopia were imaged with the NFA. Patients had no nystagmus, neurological disease or glaucoma. Nine patients had amblyopia in the right eye, and 11 patients in the left eye. RESULTS: In general, the sound eyes yielded higher thickness measures than the amblyopic eyes. These differences, however, were small, averaging only 1.5%, p = 0.6, and therefore not "statistically significant" at the p&le 0.05 level. CONCLUSIONS: Using the standard of "Statistical Significance = p< or =0.05", when amblyopic eyes are measured with the NFA, the built-in normative database may serve as the reference data

Immediate commencement of amino acid supplementation in preterm infants: effect on serum amino acid concentrations and protein kinetics on the first day of life.

To determine whether the general reluctance to begin amino acid administration to preterm infants from birth onward might lead to loss of lean body mass and impairment of growth, we measured amino acid levels and protein kinetics in 18 preterm infants. Nine infants received amino acids (1.15 +/- 0.06 gm.kg-1.day-1) and glucose (6.05 +/- 1.58 gm.kg-1.day-1), whereas the other nine infants received only glucose (6.48 +/- 1.30 gm.kg-1.day-1) from birth onward. Protein kinetics on the first postnatal day were measured with a stable isotope dilution technique with [1-13C]leucine as a tracer. No statistically significant differences were noted in blood pH, base excess, urea concentration, or glucose levels. Both total amino acid concentration and total essential amino acid concentration were significantly lower and were below the reference range in the nonsupplemented group. Plasma amino acid levels of five essential amino acids (methionine, cystine, isoleucine, leucine, arginine) were below the reference range in the nonsupplemented group, whereas only cystine was below the reference range in the supplemented group. Nitrogen retention was improved significantly by the administration of amino acids (-110 +/- 44 mg nitrogen per kilogram per day in the glucose-only group vs +10 +/- 127 mg nitrogen per kilogram per day in the group given glucose and amino acids; p = 0.001); leucine oxidation was not significantly increased in the supplemented group (41 +/- 13 mumol.kg-1.hr-1 vs 46 +/- 16 mumol.kg-1.hr-1). Leucine balance also improved significantly (-41 +/- 13 mumol.kg-1.hr-1 vs -8 +/- 16 mumol.kg-1.hr-1; p = 0.01) because of a combination of an increased amount of leucine being used for protein synthesis and a lower amount of leucine coming from protein breakdown. Plasma cystine concentration, the only amino acid below the reference range in the supplemented group, was highly predictive for protein synthesis in that group. We conclude that the administration of amino acids to preterm infants from birth onward seems safe and prevents the loss of protein mass.