Glaucoma: the retina and beyond

Over 60 million people worldwide are diagnosed with glaucomatous optic neuropathy, which is estimated to be responsible for 8.4 million cases of irreversible blindness globally. Glaucoma is associated with characteristic damage to the optic nerve and patterns of visual field loss which principally involves the loss of retinal ganglion cells (RGCs). At present, intraocular pressure (IOP) presents the only modifiable risk factor for glaucoma, although RGC and vision loss can continue in patients despite well-controlled IOP. This, coupled with the present inability to diagnose glaucoma until relatively late in the disease process, has led to intense investigations towards the development of novel techniques for the early diagnosis of disease. This review outlines our current understanding of the potential mechanisms underlying RGC and axonal loss in glaucoma. Similarities between glaucoma and other neurodegenerative diseases of the central nervous system are drawn before an overview of recent developments in techniques for monitoring RGC health is provided, including recent progress towards the development of RGC specific contrast agents. The review concludes by discussing techniques to assess glaucomatous changes in the brain using MRI and the clinical relevance of glaucomatous-associated changes in the visual centres of the brain

A compact, variable radio nebula around P Cygni

We present high spatial resolution images, at a wavelength of 6 cm, of the luminous blue variable star P Cygni. The images fully resolve the core of the stellar wind, and show that it is very clumpy. Two images were taken, separated in time by approximately a month, during which the structure in the wind has changed radically. The total flux observed has also changed significantly. We show that the clump sizes and electron densities are consistent with the radio variability being due to recombination of the ionized gas within the clumps, after key cooling lines become optically thin, causing the free-free emission to disappear. This is the first time that resolved radio images of a hot star wind have been obtained. It also represents important confirmation of a previous observation that thermal free-free wind emission can vary rapidly in a hot stellar wind

Automatic quantitative analysis of experimental primary and secondary retinal neurodegeneration: implications for optic neuropathies.

Secondary neurodegeneration is thought to play an important role in the pathology of neurodegenerative disease, which potential therapies may target. However, the quantitative assessment of the degree of secondary neurodegeneration is difficult. The present study describes a novel algorithm from which estimates of primary and secondary degeneration are computed using well-established rodent models of partial optic nerve transection (pONT) and ocular hypertension (OHT). Brn3-labelled retinal ganglion cells (RGCs) were identified in whole-retinal mounts from which RGC density, nearest neighbour distances and regularity indices were determined. The spatial distribution and rate of RGC loss were assessed and the percentage of primary and secondary degeneration in each non-overlapping segment was calculated. Mean RGC number (82 592±681) and RGC density (1695±23.3 RGC/mm(2)) in naïve eyes were comparable with previous studies, with an average decline in RGC density of 71±17 and 23±5% over the time course of pONT and OHT models, respectively. Spatial analysis revealed greatest RGC loss in the superior and central retina in pONT, but significant RGC loss in the inferior retina from 3 days post model induction. In comparison, there was no significant difference between superior and inferior retina after OHT induction, and RGC loss occurred mainly along the superior/inferior axis (~30%) versus the nasal-temporal axis (~15%). Intriguingly, a significant loss of RGCs was also observed in contralateral eyes in experimental OHT. In conclusion, a novel algorithm to automatically segment Brn3a-labelled retinal whole-mounts into non-overlapping segments is described, which enables automated spatial and temporal segmentation of RGCs, revealing heterogeneity in the spatial distribution of primary and secondary degenerative processes. This method provides an attractive means to rapidly determine the efficacy of neuroprotective therapies with implications for any neurodegenerative disorder affecting the retina

Consolidated health economic evaluation reporting standards (CHEERS) statement

<p>Economic evaluations of health interventions pose a particular challenge for reporting. There is also a need to consolidate and update existing guidelines and promote their use in a user friendly manner. The Consolidated Health Economic Evaluation Reporting Standards (CHEERS) statement is an attempt to consolidate and update previous health economic evaluation guidelines efforts into one current, useful reporting guidance. The primary audiences for the CHEERS statement are researchers reporting economic evaluations and the editors and peer reviewers assessing them for publication.</p> <p>The need for new reporting guidance was identified by a survey of medical editors. A list of possible items based on a systematic review was created. A two round, modified Delphi panel consisting of representatives from academia, clinical practice, industry, government, and the editorial community was conducted. Out of 44 candidate items, 24 items and accompanying recommendations were developed. The recommendations are contained in a user friendly, 24 item checklist. A copy of the statement, accompanying checklist, and this report can be found on the ISPOR Health Economic Evaluations Publication Guidelines Task Force website (www.ispor.org/TaskForces/EconomicPubGuidelines.asp).</p> <p>We hope CHEERS will lead to better reporting, and ultimately, better health decisions. To facilitate dissemination and uptake, the CHEERS statement is being co-published across 10 health economics and medical journals. We encourage other journals and groups, to endorse CHEERS. The author team plans to review the checklist for an update in five years.</p&gt

Selling Health Promotion to Corporate America: Uses and Abuses of the Economic Argument

Economic considerations constitute a significant factor in businesses' interest in adopting health promotion (HP) programs and in the wellness community's attempts to sell such programming to business. Substantial elements of both the business and wellness communities believe that HP programs are financially profitable, in addition to, and as a result of, improving employees' health. Examination of the foundation of this belief, however, leads to the conclusion that underlying analyses have been techni cally flawed and have ignored important costs of HP programs. This article discusses the limitations of these analyses and outlines the framework of a model that could provide a sound assessment of the economics of workplace HP programs. In general, it is expected that resultant analyses would find less direct profit potential in work place HP programs but would emphasize the cost-effectiveness of many such efforts. The latter would force recognition that health, and not profit, is the principal benefit of health promotion programming. The distinction between the cost-effectiveness and cost-saving potential of health promotion is one that all interested parties should master.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66785/2/10.1177_109019818701400106.pd

Assessing anesthetic activity through modulation of the membrane dipole potential

There is great individual variation in response to general anaesthetics leading to difficulties in optimal dosing and sometimes even accidental awareness during general anaesthesia (AAGA). AAGA is a rare but potentially devastating complication affecting between 0.1% and 2% of patients undergoing surgery. The development of novel, personalised screening techniques to accurately predict a patient's response to GA and the risk of AAGA remains an unmet clinical need. In the present study we demonstrate the principle of using a fluorescent reporter of the membrane dipole potential, di-8-ANEPPs, as a novel method to monitor anaesthetic activity using a well-described inducer/non-inducer pair. The membrane dipole potential has previously been suggested to contribute a novel mechanism of anaesthetic action (Qin et al 1995). We show the fluorescence ratio of di-8-ANEPPs changed in response to physiological concentrations of the anaesthetic 1-chloro-1,2,2-trifluorocyclobutane (F3) but not the structurally similar non-inducer 1,2-dichlorohexafluorocyclobutane (F6) to artificial membranes and in vitro retinal cell systems. Modulation of the membrane dipole provides an explanation to overcome limitations associated with alternative membrane-mediated mechanisms of GA action. Furthermore, by combining this technique with non-invasive retinal imaging technologies, we propose this technique could provide a novel and non-invasive technique to monitor GA susceptibility and identify patients at risk of AAGA

Glaucoma Rose Plot Analysis: detecting early structural progression using angular histograms

Purpose To evaluate the novel Rose Plot Analysis (RPA) in the analysis and presentation of glaucoma structural progression data. Design Case-control image analysis study using retrospective retinal imaging series. Subjects Subjects with open-angle glaucoma with at least 5 registered spectral-domain OCT scans. Methods Glaucoma RPA was developed, combining a novel application of angular histograms and dynamic cluster analysis of circumpapillary retinal nerve fiber layer (cRNFL) OCT data. Rose Plot Analysis plots were created for each eye and each visit. Significant clusters of progression were indicated in red. Three masked clinicians categorized all RPA plots (progressing, not progressing), in addition to measuring the significant RPA area. A masked OCT series assessment with linear regression of averaged global and sectoral cRNFL thicknesses was conducted as the clinical imaging standard. Main Outcome Measures Interobserver agreement was compared between RPA and the clinical imaging standard. Discriminative ability was assessed using receiver-operating characteristic curves. The time to detection of progression was compared using a Kaplan–Meier survival analysis, and the agreement of RPA with the clinical imaging standard was calculated. Results Seven hundred fourty-three scans from 98 eyes were included. Interobserver agreement was significantly greater when categorizing RPA (κ, 0.86; 95% confidence interval [CI], 0.81–0.91) compared with OCT image series (κ, 0.66; 95% CI, 0.54–0.77). The discriminative power of RPA to differentiate between eyes that were progressing and not progressing (area under the curve [AUC], 0.97; 95% CI, 0.92–1.00) was greater than that of global cRNFL thickness (AUC, 0.71; 95% CI, 0.59–0.82; P < 0.0001) and equivalent to that of sectoral cRNFL regression (AUC, 0.97; 95% CI, 0.92–1.00). A Kaplan–Meier survival analysis showed that progression was detected 8.7 months sooner by RPA than by global cRNFL linear regression (P < 0.0001) in progressing eyes but was not sooner than with sectoral cRNFL (P = 0.06). Rose Plot Analysis showed substantial agreement with the presence of significant thinning on sectoral cRNFL linear regression (κ, 0.715; 95% CI, 0.578–0.853). Conclusions Rose Plot Analysis has been shown to provide accurate and intuitive, at-a-glance data analysis and presentation that improve interobserver agreement and may aid early diagnosis of glaucomatous disease progression

Annexins in glaucoma

Glaucoma is one of the leading causes of irreversible visual loss, which has been estimated to affect 3.5% of those over 40 years old and projected to affect a total of 112 million people by 2040. Such a dramatic increase in affected patients demonstrates the need for continual improvement in the way we diagnose and treat this condition. Annexin A5 is a 36 kDa protein that is ubiquitously expressed in humans and is studied as an indicator of apoptosis in several fields. This molecule has a high calcium-dependent affinity for phosphatidylserine, a cell membrane phospholipid externalized to the outer cell membrane in early apoptosis. The DARC (Detection of Apoptosing Retinal Cells) project uses fluorescently-labelled annexin A5 to assess glaucomatous degeneration, the inherent process of which is the apoptosis of retinal ganglion cells. Furthermore, this project has conducted investigation of the retinal apoptosis in the neurodegenerative conditions of the eye and brain. In this present study, we summarized the use of annexin A5 as a marker of apoptosis in the eye. We also relayed the progress of the DARC project, developing real-time imaging of retinal ganglion cell apoptosis in vivo from the experimental models of disease and identifying mechanisms underlying neurodegeneration and its treatments, which has been applied to the first human clinical trials. DARC has potential as a biomarker in neurodegeneration, especially in the research of novel treatments, and could be a useful tool for the diagnosis and monitoring of glaucoma

Pits and fissures: Relative space contribution in fissures from sealants, prophylaxis pastes and organic remnants

The document attached has been archived with permission from the Australian Dental Association. An external link to the publisher’s copy is included.Background: Previous studies by the authors have looked at the nature of the fissure system of human permanent molars and premolars, and has provided evidence for the presence of a prismless layer of enamel. It was noted during these studies that the fissure spaces were often occupied by material other than the fissure sealant. The aim of this study was to define these materials and to look at the percentage contribution of each to the sealed fissure space. MethodS: A sample of teeth, both molars and premolars, were sealed with an unfilled fissure sealant after prophylaxis with a coloured prophylaxis paste. In one group, the crown of the tooth was removed by dissolution in hydrochloric acid following placement of the sealant. This revealed a negative image of the fissure system and its contents. The second group of teeth was sectioned following sealing, and the contents of the fissure space were analyzed. Results: The negative image of the fissure system displayed the fissure contents by colour and the sectioned teeth were able to be computer analyzed to establish the relative contribution of sealant, prophylaxis paste and organic material to the fissure space. Conclusions: Sealant contribution was in the range of 14- 96 per cent, prophylaxis paste from 0-50 per cent and organic remnants 0-55 per cent. The presence of these last two components could contribute to sealant loss