The Relative Odds of Progressing by Structural and Functional Tests in Glaucoma.

PurposeThe purpose of this study was to evaluate the effect of disease severity and number of tests acquired during follow-up on the relative odds of identifying progression by structural or functional tests in glaucoma.MethodsThis was an observational cohort study involving 462 eyes of 305 patients with glaucoma and 62 eyes of 49 healthy subjects. Glaucoma patients and healthy subjects were followed for an average of 3.6 ± 0.9 and 3.8 ± 0.9 years, with a median (interquantile range) of 8 (6-9) and 7 (6-8) visits, respectively. At each visit, subjects underwent visual field assessment with standard automated perimetry (SAP) and retinal nerve fiber layer (RNFL) evaluation by spectral-domain optical coherence tomography (SD-OCT). Slopes of change in SAP mean sensitivity and OCT RNFL thickness over time were estimated by linear regression using progressively cumulative visits over time. Cutoff values for age-related expected rates of change for each test were obtained from the healthy group. Progression by SD-OCT and/or SAP was determined if the slope of change was statistically significant and also lower (faster) than the fifth percentile cutoff calculated from the healthy group. A generalized estimating equation logistic regression model was used to evaluate the relative odds of progressing by OCT versus SAP in glaucoma eyes.ResultsEyes with less severe disease at baseline had a higher chance of being detected as progressing by SD-OCT but not by SAP, whereas an increase in disease severity at baseline increased the chance that the eye would be detected as progressing by SAP but not SD-OCT. Each 1 dB higher MD was associated with a 5% increase in the odds of detecting progression by SD-OCT versus SAP (odds ratio = 1.05 per 1 dB; 95% confidence interval: 1.01-1.09; P = 0.005).ConclusionsThe ability to detect glaucoma progression by SAP versus SD-OCT is significantly influenced by the stage of disease. Our results may provide useful information for guiding clinicians on the relative utility of these tests for detecting change throughout the disease continuum

Fear of falling and postural reactivity in patients with glaucoma

Purpose To investigate the relationship between postural metrics obtained by dynamic visual stimulation in a virtual reality environment and the presence of fear of falling in glaucoma patients. Methods This cross-sectional study included 35 glaucoma patients and 26 controls that underwent evaluation of postural balance by a force platform during presentation of static and dynamic visual stimuli with head-mounted goggles (Oculus Rift). In dynamic condition, a peripheral translational stimulus was used to induce vection and assess postural reactivity. Standard deviations of torque moments (SDTM) were calculated as indicative of postural stability. Fear of falling was assessed by a standardized questionnaire. The relationship between a summary score of fear of falling and postural metrics was investigated using linear regression models, adjusting for potentially confounding factors. Results Subjects with glaucoma reported greater fear of falling compared to controls (-0.21 vs. 0.27P = 0.039). In glaucoma patients, postural metrics during dynamic visual stimulus were more associated with fear of falling (R-2 = 18.8%P = 0.001) than static (R-2 = 3.0%P = 0.005) and dark field (R-2 = 5.7%P = 0.007) conditions. In the univariable model, fear of falling was not significantly associated with binocular standard perimetry mean sensitivity (P = 0.855). In the multivariable model, each 1 Nm larger SDTM in anteroposterior direction during dynamic stimulus was associated with a worsening of 0.42 units in the fear of falling questionnaire score (P = 0.001). Conclusion In glaucoma patients, postural reactivity to a dynamic visual stimulus using a virtual reality environment was more strongly associated with fear of falling than visual field testing and traditional balance assessment.National Institutes of Health/National Eye Institute [EY021818]Brazilian National Council for Scientific and Technological Development (CNPq) [233829/2014-8]Alcon Laboratories (Fort Worth, TX)Bausch & Lomb (Garden City, NY)Carl Zeiss Meditec (Jena, Germany)Heidelberg Engineering (Heidelberg, Germany)Merck (White House Station, NJ)Allergan (Irvine, CA)Sensimed (Lausanne, Switzerland)Topcon (Livermore, CA)Reichert (Dewey, NY)National Eye Institute (Bethesda, MD)Novartis (Basel, Switzerland)nGoggle (San Diego, CA)Duke Univ, Duke Eye Ctr, Durham, NC 27708 USADuke Univ, Dept Ophthalmol, Durham, NC 27708 USAUniv Fed Sao Paulo, Dept Ophthalmol & Vis Sci, Sao Paulo, BrazilUniv Calif San Diego, Dept Ophthalmol, La Jolla, CA 92093 USAUniv Fed Sao Paulo, Dept Ophthalmol & Vis Sci, Sao Paulo, BrazilCNPq [233829/2014-8]Web of Scienc

Macular Ganglion Cell Inner Plexiform Layer Thickness in Glaucomatous Eyes with Localized Retinal Nerve Fiber Layer Defects

Purpose: To investigate macular ganglion cell–inner plexiform layer (mGCIPL) thickness in glaucomatous eyes with visible localized retinal nerve fiber layer (RNFL) defects on stereophotographs. Methods: 112 healthy and 149 glaucomatous eyes from the Diagnostic Innovations in Glaucoma Study (DIGS) and the African Descent and Glaucoma Evaluation Study (ADAGES) subjects had standard automated perimetry (SAP), optical coherence tomography (OCT) imaging of the macula and optic nerve head, and stereoscopic optic disc photography. Masked observers identified localized RNFL defects by grading of stereophotographs. Result: 47 eyes had visible localized RNFL defects on stereophotographs. Eyes with visible localized RNFL defects had significantly thinner mGCIPL thickness compared to healthy eyes (68.3 ± 11.4 μm versus 79.2 ± 6.6 μm respectively, P<0.001) and similar mGCIPL thickness to glaucomatous eyes without localized RNFL defects (68.6 ± 11.2 μm, P = 1.000). The average mGCIPL thickness in eyes with RNFL defects was 14% less than similarly aged healthy controls. For 29 eyes with a visible RNFL defect in just one hemiretina (superior or inferior) mGCIPL was thinnest in the same hemiretina in 26 eyes (90%). Eyes with inferior-temporal RNFL defects also had significantly thinner inferior-temporal mGCIPL (P<0.001) and inferior mGCIPL (P = 0.030) compared to glaucomatous eyes without a visible RNFL defect. Conclusion: The current study indicates that presence of a localized RNFL defect is likely to indicate significant macular damage, particularly in the region of the macular that topographically corresponds to the location of the RNFL defect

Asymmetric Macular Structural Damage Is Associated With Relative Afferent Pupillary Defects in Patients With Glaucoma

PURPOSE. We examined the relationship between relative afferent pupillary defects (RAPDs) and macular structural damage measured by macular thickness and macular ganglion cell-inner plexiform layer (mGCIPL) thickness in patients with glaucoma. METHODS. A cross-sectional study was done of 106 glaucoma patients and 85 healthy individuals from the Diagnostic Innovations in Glaucoma Study. All subjects underwent standard automated perimetry (SAP) and optic nerve and macular imaging using Cirrus Spectral Domain Optical Coherence Tomography (SDOCT). Glaucoma was defined as repeatable abnormal SAP or progressive glaucomatous changes on stereo photographs. Pupil responses were assessed using an automated pupillometer, which records the magnitude of RAPD (RAPD score), with additional RAPD scores recorded for each of a series of colored stimuli (blue, red, green, and yellow). The relationship between RAPD score and intereye differences (right minus left eye) in circumpapillary retinal nerve fiber layer (cpRNFL) thickness, mGCIPL, macular thickness, and SAP mean deviation (MD), was examined using linear regression. RESULTS. There was fair correlation between RAPD score and asymmetric macular structural damage measured by intereye difference in mGCIPL thickness (R-2 = 0.285, P < 0.001). The relationship between RAPD score and intereye difference in macular thickness was weaker (R-2 = 0.167, P < 0.001). Intereye difference in cpRNFL thickness (R-2 = 0.350, P < 0.001) and SAP MD (R-2 = 0.594, P < 0.001) had stronger association with RAPD scores compared to intereye difference in mGCIPL and macular thickness. CONCLUSIONS. Objective assessment of pupillary responses using a pupillometer was associated with asymmetric macular structural damage in patients with glaucoma.National Institutes of Health/National Eye InstituteResearch to Prevent Blindness (New York, NY, USA)AlconAllerganPfizerMerckSantenBrazilian National Research Council-CAPESUniv Calif San Diego, Hamilton Glaucoma Ctr, 9500 Gilman Dr, La Jolla, CA 92093 USAUniv Calif San Diego, Dept Ophthalmol, La Jolla, CA 92093 USAUniv Fed Sao Paulo, Dept Ophthalmol, Sao Paulo, BrazilUniv Edinburgh, Princess Alexandra Eye Pavil, Edinburgh EH8 9YL, Midlothian, ScotlandUniv Edinburgh, Dept Ophthalmol, Edinburgh EH8 9YL, Midlothian, ScotlandUniv Fed Sao Paulo, Dept Ophthalmol, Sao Paulo, BrazilNIH/NEI: EY021818NIH/NEI: EY11008NIH/NEI: EY14267NIH/NEI: EY019869NIH/NEI: P30EY022589CAPES: 12309-13-3Web of Scienc

Can we predict who will benefit from the deep inspiration breath hold (DIBH) technique for breast cancer irradiation?

Background: The objective was to explore the clinical use of an “in-house” prototype developed to monitor respiratory motion to implement the deep inspiration breath hold technique (DIBH), compare dosimetric differences, and assess whether simple anatomic metrics measured on free breathing (FB) computed tomography scan (CT) can help in selecting patients that would benefit the most from the technique. Materials and methods: A prospective study was conducted on patients with left breast cancer with an indication of adjuvant radiotherapy for breast only. Treatment simulation consisted of four series of CTs: the first during FB and three in DIBH to assess the reproducibility and stability of apnea. Contouring was based on the RTOG atlas, and planning was done in both FB and DIBH. Dosimetric and geometric parameters were assessed and compared between FB and DIBH. Results: From June 2020 to December 2021, 30 patients with left breast cancer were recruited. Overall, the DIBH technique presented a mean dose reduction of 24% in the heart and 30% in the left anterior descendent coronary artery (LAD) (p &lt; 0.05). The only geometric parameter correlated to a 30% dose reduction in the mean heart dose and LAD doses was the anterolateral distance from the heart to the chest wall of at least 1.5 cm measured on FB (p &lt; 0.0001). Conclusion: The prototype enabled the use of the DIBH technique with dose reductions in the heart and LAD. The benefit of the DIBH technique can be predicted on FB CT by measuring the distance between the heart and chest wall at the treatment isocenter

Signal transduction-related responses to phytohormones and environmental challenges in sugarcane

BACKGROUND: Sugarcane is an increasingly economically and environmentally important C4 grass, used for the production of sugar and bioethanol, a low-carbon emission fuel. Sugarcane originated from crosses of Saccharum species and is noted for its unique capacity to accumulate high amounts of sucrose in its stems. Environmental stresses limit enormously sugarcane productivity worldwide. To investigate transcriptome changes in response to environmental inputs that alter yield we used cDNA microarrays to profile expression of 1,545 genes in plants submitted to drought, phosphate starvation, herbivory and N(2)-fixing endophytic bacteria. We also investigated the response to phytohormones (abscisic acid and methyl jasmonate). The arrayed elements correspond mostly to genes involved in signal transduction, hormone biosynthesis, transcription factors, novel genes and genes corresponding to unknown proteins. RESULTS: Adopting an outliers searching method 179 genes with strikingly different expression levels were identified as differentially expressed in at least one of the treatments analysed. Self Organizing Maps were used to cluster the expression profiles of 695 genes that showed a highly correlated expression pattern among replicates. The expression data for 22 genes was evaluated for 36 experimental data points by quantitative RT-PCR indicating a validation rate of 80.5% using three biological experimental replicates. The SUCAST Database was created that provides public access to the data described in this work, linked to tissue expression profiling and the SUCAST gene category and sequence analysis. The SUCAST database also includes a categorization of the sugarcane kinome based on a phylogenetic grouping that included 182 undefined kinases. CONCLUSION: An extensive study on the sugarcane transcriptome was performed. Sugarcane genes responsive to phytohormones and to challenges sugarcane commonly deals with in the field were identified. Additionally, the protein kinases were annotated based on a phylogenetic approach. The experimental design and statistical analysis applied proved robust to unravel genes associated with a diverse array of conditions attributing novel functions to previously unknown or undefined genes. The data consolidated in the SUCAST database resource can guide further studies and be useful for the development of improved sugarcane varieties

Hyperoxemia and excess oxygen use in early acute respiratory distress syndrome : Insights from the LUNG SAFE study

Publisher Copyright: © 2020 The Author(s). Copyright: Copyright 2020 Elsevier B.V., All rights reserved.Background: Concerns exist regarding the prevalence and impact of unnecessary oxygen use in patients with acute respiratory distress syndrome (ARDS). We examined this issue in patients with ARDS enrolled in the Large observational study to UNderstand the Global impact of Severe Acute respiratory FailurE (LUNG SAFE) study. Methods: In this secondary analysis of the LUNG SAFE study, we wished to determine the prevalence and the outcomes associated with hyperoxemia on day 1, sustained hyperoxemia, and excessive oxygen use in patients with early ARDS. Patients who fulfilled criteria of ARDS on day 1 and day 2 of acute hypoxemic respiratory failure were categorized based on the presence of hyperoxemia (PaO2 > 100 mmHg) on day 1, sustained (i.e., present on day 1 and day 2) hyperoxemia, or excessive oxygen use (FIO2 ≥ 0.60 during hyperoxemia). Results: Of 2005 patients that met the inclusion criteria, 131 (6.5%) were hypoxemic (PaO2 < 55 mmHg), 607 (30%) had hyperoxemia on day 1, and 250 (12%) had sustained hyperoxemia. Excess FIO2 use occurred in 400 (66%) out of 607 patients with hyperoxemia. Excess FIO2 use decreased from day 1 to day 2 of ARDS, with most hyperoxemic patients on day 2 receiving relatively low FIO2. Multivariate analyses found no independent relationship between day 1 hyperoxemia, sustained hyperoxemia, or excess FIO2 use and adverse clinical outcomes. Mortality was 42% in patients with excess FIO2 use, compared to 39% in a propensity-matched sample of normoxemic (PaO2 55-100 mmHg) patients (P = 0.47). Conclusions: Hyperoxemia and excess oxygen use are both prevalent in early ARDS but are most often non-sustained. No relationship was found between hyperoxemia or excessive oxygen use and patient outcome in this cohort. Trial registration: LUNG-SAFE is registered with ClinicalTrials.gov, NCT02010073publishersversionPeer reviewe