Validation of Concentric Rings Method as a Topographic Measure of Retinal Nonperfusion in Ultra-Widefield Fluorescein Angiography

PURPOSE: To validate the use of concentric rings as a method to measure topographic area of retinal nonperfusion in ultra-widefield angiography with the ischemic index method, which is the most frequently used method to measure nonperfusion in ultra-widefield angiography. DESIGN: Validation study and reliability analysis. METHODS: setting: Single-center study performed at National Institute for Health Research Moorfields Biomedical Research Centre, London, United Kingdom. STUDY POPULATION: Twenty-eight ultra-widefield angiogram images of eyes with central retinal vein occlusion. OBSERVATION PROCEDURE: The concentric rings method consists of 6 macula-centered concentric rings divided into 12 segments each. Each image was graded by 5 graders using both the concentric rings and the ischemic index methods. MAIN OUTCOME MEASURES: Agreement between the 2 methods was calculated using the intraclass correlation coefficient. Intertest agreement, intergrader agreement, test-retest reliability, and the time taken to grade using these 2 methods were compared. RESULTS: The intertest agreement between concentric rings method and ischemic index method was 0.965. The intergrader agreement was 0.910 for the concentric rings method and 0.898 with the ischemic index method. The test-retest reliability was 0.975 for the rings and 0.979 for the ischemic index. Average grading time per image was 187 s and 297 s for the concentric rings method and ischemic index method, respectively, P < .001. CONCLUSION: The concentric rings method has an "almost-perfect" intergrader agreement and intertest agreement with the ischemic index method, with a shorter grading time

The Relationship Between Retinal Vessel Oxygenation and Spatial Distribution of Retinal Nonperfusion in Retinal Vascular Diseases

Purpose: We study the relationship between retinal vessel oxygenation and the spatial distribution of retinal nonperfusion using ultrawide field angiography in eyes with retinal vascular diseases. Methods: This prospective single center study recruited 57 eligible eyes from 44 patients with retinal vascular diseases. Retinal oximetry measurements were obtained using the Oxymap T1 device to determine the arteriovenous (AV) difference. Retinal nonperfusion was measured from ultrawide field angiography images taken with the Optos 200TX system and superimposing the images with the concentric rings template to determine the area and distribution of retinal nonperfusion. Results: Seven (12.3%) eyes had a diagnosis of a branch or hemiretinal vein occlusion, 24 (42.1%) with central retinal vein occlusion and 26 (45.6%) with diabetic retinopathy (11 [19.3%] nonproliferative and 15 [26.3%] proliferative diabetic retinopathy). The correlation between the total area of retinal nonperfusion with the AV difference controlling for age was not statistically significant (R = -0.103, P = 0.449). However, when analyzing the correlation of AV difference with the area of retinal nonperfusion in the posterior pole controlling for age and peripheral nonperfusion, this was significant (R = -0.295, P = 0.029). This was not significant for the area of retinal nonperfusion in the periphery while controlling for posterior pole nonperfusion and age (R = 0.124, P = 0.368). Conclusions: Retinal nonperfusion has a negative correlation with AV difference measured on retinal oximetry. This correlation is significant in the posterior pole, but not in the peripheral retina

Retinal non-perfusion in the posterior pole is associated with increased risk of neovascularization in central retinal vein occlusion.

PURPOSE: To review the definition of ischaemic central retinal vein occlusion (CRVO) and stratify the risk of neovascular complication based on wider areas of visible retinal non-perfusion. DESIGN: Retrospective consecutive case series and image analysis study METHODS: Setting: Moorfields Eye Hospital, London, United Kingdom. STUDY POPULATION: 42 consecutive treatment naïve eyes with CRVO imaged with ultra-widefield angiography with a minimum of 12 months follow-up. OBSERVATION PROCEDURE: The spatial location and total area of retinal non-perfusion (measured in disc areas, DA) were determined using the validated concentric rings method. The area was corrected for projection distortion. The images were graded by two retinal physicians and average measurements used. MAIN OUTCOME MEASURES: Development of neovascular complications. RESULTS: The percentage of eyes developing new vessels increased from none in eyes with less than 10 DA of non-perfusion in total, to 14.3% in eyes with 10-30DA, 20.0% for 30-75DA and 80% risk with 75-150DA of non-perfusion. From 13 (31.0%) eyes with a perfused posterior pole (an area encompassing a five disc diameter radius centered at the fovea) and more than 10DA of non-perfusion isolated in the periphery (beyond the posterior pole), only one (7.7%) eye developed new vessels, OR 0.12 [95% CI:0.01,1.03]. Comparatively, for 13 (31.0%) eyes with more than 10DA of non-perfusion in the posterior pole, 11 (84.6%) developed new vessels, OR 74.25 [95% CI: 9.26, 595.30], p<0.001. CONCLUSION: With ultra-widefield angiography, we have ascertained that posterior pole non-perfusion of more than 10DA remains the key risk factor for new vessel development compared to areas of non-perfusion confined to the periphery

Quantifying Retinal Area in Ultra-Widefield Imaging Using a 3-Dimensional Printed Eye Model

Purpose: To study the effects of different axial lengths on ultra-widefield imaging to determine the presence of distortion in images despite software correction and calculate an enlargement factor based on angular location. / Design: Experimental image analysis study. / Study Objects: Three 3-dimensional printed model eyes simulating eyes with axial lengths of 22, 24, and 26 mm. Each model has a grid of rings 9° apart centered at the posterior pole. / Methods: Single-center study performed at the National Institute for Health Research Moorfields Biomedical Research Centre (London, UK). Each model was imaged using Optos 200TX (Optos, Dunfermline, UK). Two images for each model eye that were corrected using V2 Vantage Pro software (Optos) were used for analysis and the average values obtained. Each image inter-ring area was measured using ImageJ to obtain a measured image area in pixel and square millimeters. This was compared with the true calculated object inter-ring area and an enlargement factor was determined. / Main Outcome Measures: Measured image inter-ring area in pixels and square millimeters. True calculated object inter-ring area in square millimeters. / Results: The enlargement factor of the rings gradually increases toward the periphery with factors of 1.4 at 45° and 1.9 at the equator. The axial lengths did not affect the enlargement factor of the rings imaged in 3 different model eyes (P = 0.9512). The anterior equator exhibits a significant distortion despite the software correction. / Conclusion: The enlargement factor depends on angular location and not axial length. The enlargement factors can be used in clinical practice to more accurately measure area in ultra-widefield imaging

Aortic dissection at the University hospital of the West Indies: A 20-year clinicopathological study of autopsy cases

<p>Abstract</p> <p>Background</p> <p>An autopsy study of aortic dissection (AD) at our institution was previously reported. In the approximately 20 years since then, however, many aspects of diagnosis and treatment of this disease have changed, with a fall in mortality reported in many centers around the world. An impression amongst our pathologists that, there might be an increase in the prevalence of AD in the autopsy service at our hospital, since that earlier report, led to this repeated study, in an attempt to validate that notion. We also sought to identify any changes in clinicopathological features between the two series or any occurring during this study period itself.</p> <p>Findings</p> <p>All cases of AD identified at autopsy, during the 20-year period since the conclusion of the last study, were collected and pertinent clinical and pathological data were analyzed and compared, both within the two decades of this study period and against the results of the last study.</p> <p>Fifty-six cases comprised this study group including 36 males and 20 females, with a mean age of 63.9 years. There were, more patients in the second decade (n = 33; 59%) compared with the first decade (n = 23; 41%). Hypertension as a risk factor was identified in 52 (93%) cases and rupture occurred in 49 (88%) cases. A clinical diagnosis of AD was considered prior to surgery or autopsy in 25 (45%) cases overall, more during the second decade. Surgery was attempted in 25% of all cases with an increase in the second decade compared with the first.</p> <p>Conclusions</p> <p>Compared with the earlier review, a variety of changes in the profile of patients with AD in the autopsy service has been noted, including a reversal in the female predominance seen previously. Other observations include an increase in cases where the correct clinical diagnosis was considered and in which surgical treatment was attempted, changes also evident when the second decade of the present study was compared with the earlier decade. Overall, there were many positive trends. However, areas that could still be improved include an increased index of suspicion for the diagnosis of AD and perhaps in the initiation of treatment, earlier, in those cases where the correct diagnosis was considered.</p

Revision and Update of the Consensus Definitions of Invasive Fungal Disease From the European Organization for Research and Treatment of Cancer and the Mycoses Study Group Education and Research Consortium.

BACKGROUND: Invasive fungal diseases (IFDs) remain important causes of morbidity and mortality. The consensus definitions of the Infectious Diseases Group of the European Organization for Research and Treatment of Cancer and the Mycoses Study Group have been of immense value to researchers who conduct clinical trials of antifungals, assess diagnostic tests, and undertake epidemiologic studies. However, their utility has not extended beyond patients with cancer or recipients of stem cell or solid organ transplants. With newer diagnostic techniques available, it was clear that an update of these definitions was essential. METHODS: To achieve this, 10 working groups looked closely at imaging, laboratory diagnosis, and special populations at risk of IFD. A final version of the manuscript was agreed upon after the groups' findings were presented at a scientific symposium and after a 3-month period for public comment. There were several rounds of discussion before a final version of the manuscript was approved. RESULTS: There is no change in the classifications of "proven," "probable," and "possible" IFD, although the definition of "probable" has been expanded and the scope of the category "possible" has been diminished. The category of proven IFD can apply to any patient, regardless of whether the patient is immunocompromised. The probable and possible categories are proposed for immunocompromised patients only, except for endemic mycoses. CONCLUSIONS: These updated definitions of IFDs should prove applicable in clinical, diagnostic, and epidemiologic research of a broader range of patients at high-risk

The usefulness of contrast during exercise echocardiography for the assessment of systolic pulmonary pressure

<p>Abstract</p> <p>Background</p> <p>The systolic pulmonary artery pressure (PAPs) can be accurately estimated, non-invasively, using continuous-wave Doppler (CWD) ultrasound measurement of the peak velocity of a tricuspid regurgitant (TR) jet.</p> <p>However, it is often difficult to obtain adequate tricuspid regurgitation signals for measurement of PAPs, what could lead to its underestimation. Therefore, utilization of air-blood-saline contrast has been implemented for the improvement of Doppler signal in several clinical contexts.</p> <p>It is now recommended in the evaluation of patients with pulmonary hypertension. Physical activity is severely restricted in patients with PAH, being exertional dypnea the most typical symptom. Exercise stress echo-Doppler imaging allows assessment of the response to exercise. It is an excellent screening test for patients with suspected PAH. Our purpose was to evaluate the value and accuracy of agitated saline with blood contrast echocardiography, in the improvement of the Doppler signal, to quantify PAPs during treadmill exercise-echocardiography.</p> <p>Purpose</p> <p>To evaluate the value of contrast echocardiography, using agitated saline with blood, in the improvement of the Doppler signal used to quantify the pulmonary artery systolic pressure during exercise.</p> <p>Methods</p> <p>From a total of 41 patients (pts), we studied 38 pts (93%), 35 women, aged 54 ± 12 years-old. 27 with the diagnosis of systemic sclerosis, 10 with history of pulmonary embolism and one patient with a suspected idiopathic PAH, who were referred to the Unity of Heart Failure and Pulmonary Hypertension for screening of PAH. According to the Unity protocol, a transthoracic echocardiogram was made, in left decubitus (LD), with evaluation of right ventricle-right atria gradient (RV/RAg). A peripheral venous access was obtained, with a 3-way stopcock and the patients were placed in orthostatism (O), with a new evaluation of RV/RAg. Exercise echocardiography (EE) was begun, with evaluation of RV/RAg at peak exercise (P) and afterwards agitated saline (8 cc with 1 cc of air and 1 cc of blood) was injected, followed by a new evaluation of RV/RAg (PC) and then the interruption of the EE. Pulmonary Hypertension was diagnosed when RV/RAg at the end of the exercise was superior to 40 mmHg.</p> <p>Results</p> <p>The quality of Doppler signal was deteriorated in 5 pts, maintained in 6 pts and improved in 26 pts, with the use of contrast. In one patient, an interventricular septal defect was diagnosed. In 6 pts, a Doppler signal was only obtained with the use of contrast. In 15 pts, a RV/RAg superior to 40 mmHg was only obtained with the use of contrast. Of these, 9 have already been submitted to right heart cathetherism, that confirmed the diagnosis of pulmonary hypertension in 5 of them (56%). RV/RAg (P) was 44 ± 11 mmHg and RV/RAg (PC) was 54 ± 11 mmHg, p < 0,001.</p> <p>Conclusion</p> <p>1. The method is applicable in a large number of patients. 2. RV/RA gradients obtained at peak exercise are higher with the use of contrast, and the clinical meaning of this difference should be evaluated in a larger number of pts submitted to right heart cathetherism. The high number of false positives should lead to a higher diagnostic threshold. 3. This method seems to have relevant clinical value in the diagnosis of pulmonary arterial hypertension.</p

Different modes of state transitions determine pattern in the Phosphatidylinositide-Actin system

<p>Abstract</p> <p>Background</p> <p>In a motile polarized cell the actin system is differentiated to allow protrusion at the front and retraction at the tail. This differentiation is linked to the phosphoinositide pattern in the plasma membrane. In the highly motile <it>Dictyostelium </it>cells studied here, the front is dominated by PI3-kinases producing PI(3,4,5)tris-phosphate (PIP3), the tail by the PI3-phosphatase PTEN that hydrolyses PIP3 to PI(4,5)bis-phosphate. To study de-novo cell polarization, we first depolymerized actin and subsequently recorded the spontaneous reorganization of actin patterns in relation to PTEN.</p> <p>Results</p> <p>In a transient stage of recovery from depolymerization, symmetric actin patterns alternate periodically with asymmetric ones. The switches to asymmetry coincide with the unilateral membrane-binding of PTEN. The modes of state transitions in the actin and PTEN systems differ. Transitions in the actin system propagate as waves that are initiated at single sites by the amplification of spontaneous fluctuations. In PTEN-null cells, these waves still propagate with normal speed but loose their regular periodicity. Membrane-binding of PTEN is induced at the border of a coherent PTEN-rich area in the form of expanding and regressing gradients.</p> <p>Conclusions</p> <p>The state transitions in actin organization and the reversible transition from cytoplasmic to membrane-bound PTEN are synchronized but their patterns differ. The transitions in actin organization are independent of PTEN, but when PTEN is present, they are coupled to periodic changes in the membrane-binding of this PIP3-degrading phosphatase. The PTEN oscillations are related to motility patterns of chemotaxing cells.</p

A Secure Semi-Field System for the Study of Aedes aegypti

Novel vector control strategies require validation in the field before they can be widely accepted. Semi-field system (SFS) containment facilities are an intermediate step between laboratory and field trials that offer a safe, controlled environment that replicates field conditions. We developed a SFS laboratory and cage complex that simulates an urban house and yard, which is the primary habitat for Aedes aegypti, the mosquito vector of dengue in Cairns Australia. The SFS consists of a Quarantine Insectary Level-2 (QIC-2) laboratory, containing 3 constant temperature rooms, that is connected to two QIS-2 cages for housing released mosquitoes. Each cage contains the understory of a “Queenslander” timber house and associated yard. An automated air conditioning system keeps temperature and humidity to within 1°C and 5% RH of ambient conditions, respectively. Survival of released A. aegypti was high, especially for females. We are currently using the SFS to investigate the invasion of strains of Wolbachia within populations of A. aegypti