Rhegmatogenous retinal detachment in Scotland: research design and methodology

<p>Abstract</p> <p>Background</p> <p>Rhegmatogenous retinal detachment (RRD) is a potentially blinding condition and a common cause of ocular morbidity. Establishing an accurate estimate of disease incidence and distribution is an important first step in assessing the healthcare burden related to this condition and in subsequent planning and provision of treatment strategies. The aim of this study is to obtain a first estimate incidence of RRD in Scotland, to estimate the incidence of familial RRD and to describe the known associations of RRD within the study population.</p> <p>Methods/Design</p> <p>We have established a national prospective observational study seeking to identify and recruit all incident cases of RRD in the Scottish population over a 2 year period. After fully informed consent, all participants will have a blood sample taken and a full medical history and clinical examination performed including visual acuity, refraction, slit-lamp examination, intra-ocular pressure measurement and detailed fundal examination. We describe the study design and protocol.</p> <p>Conclusion</p> <p>This study will provide the first estimate of the annual incidence of RRD in Scotland. The findings of this study will be important in estimating the burden of disease and in the planning of future health care policy related to this condition. This study will also establish a genetic resource for a genome wide association study to investigate if certain genetic variants predispose to RRD.</p

Transcriptomic Analysis of Human Retinal Detachment Reveals Both Inflammatory Response and Photoreceptor Death

Background Retinal detachment often leads to a severe and permanent loss of vision and its therapeutic management remains to this day exclusively surgical. We have used surgical specimens to perform a differential analysis of the transcriptome of human retinal tissues following detachment in order to identify new potential pharmacological targets that could be used in combination with surgery to further improve final outcome. Methodology/Principal Findings Statistical analysis reveals major involvement of the immune response in the disease. Interestingly, using a novel approach relying on coordinated expression, the interindividual variation was monitored to unravel a second crucial aspect of the pathological process: the death of photoreceptor cells. Within the genes identified, the expression of the major histocompatibility complex I gene HLA-C enables diagnosis of the disease, while PKD2L1 and SLCO4A1 -which are both down-regulated- act synergistically to provide an estimate of the duration of the retinal detachment process. Our analysis thus reveals the two complementary cellular and molecular aspects linked to retinal detachment: an immune response and the degeneration of photoreceptor cells. We also reveal that the human specimens have a higher clinical value as compared to artificial models that point to IL6 and oxidative stress, not implicated in the surgical specimens studied here. Conclusions/Significance This systematic analysis confirmed the occurrence of both neurodegeneration and inflammation during retinal detachment, and further identifies precisely the modification of expression of the different genes implicated in these two phenomena. Our data henceforth give a new insight into the disease process and provide a rationale for therapeutic strategies aimed at limiting inflammation and photoreceptor damage associated with retinal detachment and, in turn, improving visual prognosis after retinal surgery

Global Research Alliance N2O chamber methodology guidelines: considerations for automated flux measurement

Nitrous oxide (N2O) emissions are highly episodic in response to nitrogen additions and changes in soil moisture. Automated gas sampling provides the necessary high temporal frequency to capture these emission events in real time, ensuring the development of accurate N2O inventories and effective mitigation strategies to reduce global warming. This paper outlines the design and operational considerations of automated chamber systems including chamber design and deployment, frequency of gas sampling, and options in terms of the analysis of gas samples. The basic hardware and software requirements for automated chambers are described, including the major challenges and obstacles in their implementation and operation in a wide range of environments. Detailed descriptions are provided of automated systems that have been deployed to assess the impacts of agronomy on the emissions of N2O and other significant greenhouse gases. This information will assist researchers across the world in the successful deployment and operation of automated N2O chamber systems

Does feedback trading drive returns of cross-listed shares?

This paper examines the role of cross-listing in stock return dynamics with particular reference to feedback trading based on a sample of five most frequently traded cross-listed shares. We find that a long-run equilibrium relationship among the cross-listed share prices exists, but find no evidence of long-run co-movements among different shares traded in the same exchange. Furthermore, the VAR Granger causality tests indicate bi-directional feedback relations among the returns of cross-listed shares, while there is no consistent causality among different stocks within the markets. We also find that the cross-listed shares demonstrate strong volatility spillovers, which is driven by the covariance structure that are formed by variance and correlation terms. In addition, we report liquidity spillover effects and spillovers running from liquidity to volatility for some firms but no evidence that spillover effects run from volatility to liquidity

The Genetic Architecture of Non-Syndromic Rhegmatogenous Retinal Detachment

Rhegmatogenous retinal detachment (RRD) is the most common form of retinal detachment (RD), affecting 1 in 10,000 patients per year. The condition has significant ocular morbidity, with a sizeable proportion of patients obtaining poor visual outcomes. Despite this, the genetics underpinning Idiopathic Retinal Detachment (IRD) remain poorly understood; this is likely due to small sample sizes in relevant studies. The majority of research pertains to the well-characterised Mende lian syndromes, such as Sticklers and Wagners, associated with RRD. Nevertheless, in recent years, there has been an increasing body of literature identifying the common genetic mutations and mechanisms associated with IRD. Several recent Genomic Wide Association Studies (GWAS) studies have identified a number of genetic loci related to the development of IRD. Our review aims to provide an up-to-date summary of the significant genetic mechanisms and associations of Idiopathic RRD

Ozurdex (a slow-release dexamethasone implant) in proliferative vitreoretinopathy:study protocol for a randomised controlled trial

BACKGROUND: Proliferative vitreoretinopathy (PVR) is the commonest cause of late anatomical failure in rhegmatogenous retinal detachment. Visual and anatomical outcomes remain poor despite advances in vitreoretinal surgical techniques with reported primary failure rates of up to nearly 50%. Numerous adjunctive medications have been evaluated in clinical trials with no agent gaining widespread acceptance and use. This study was designed to investigate the benefits of using a slow-release dexamethasone implant delivered intra-operatively in patients undergoing vitrectomy surgery for retinal detachment with established PVR. METHODS/DESIGN: For the study, 140 patients requiring vitrectomy surgery with silicone oil for retinal detachment with established PVR will be randomised to receive either standard treatment or study treatment in a 1:1 treatment allocation ratio. Both groups will receive the standard surgical treatment appropriate for their eye condition and routine peri-operative treatment and care, differing only in the addition of the supplementary adjunctive agent in the treatment group. The investigated primary outcome measure is stable retinal reattachment with removal of silicone oil without additional vitreoretinal surgical intervention at 6 months. DISCUSSION: This is the first randomised controlled clinical trial to investigate the use of an adjunctive slow-release dexamethasone implant in patients undergoing vitrectomy surgery for retinal detachments with proliferative vitreoretinopathy. TRIAL REGISTRATION: EudraCT No: 2011-004498-96

Functional outcome and prognostic factors in 304 eyes managed by retinectomy

BACKGROUND: This study was undertaken to relate the anatomic and functional results of patients who underwent retinectomy for complex retinal detachment (RD) to preoperative prognostic variables. METHODS: Three hundred and four eyes of 302 patients whose surgery involved retinectomy were included in the analysis. All eyes had established proliferative vitreoretinopathy (PVR grade C). The main outcome measures were (1) postoperative visual acuity of 6/24 or better, (2) status of the retina at the end of follow-up, and (3) incidence of hypotony whilst under review. RESULTS: PVR was secondary to rhegmatogenous RD in 237 eyes (78%), posterior trauma in 51 eyes (16.8%), tractional RD in vasoproliferative vasculitides in 12 eyes (4%), acute retinal necrosis in 2 eyes and endophthalmitis in 2 eyes. Complete reattachment rate after one operation was 51%, with final complete reattachment success rate of 72%. The visual acuity improved in 138 eyes (45%), remained the same in 73 eyes (24%) and became worse in 89 cases (29%). Postoperative visual acuity of 6/24 or better was significantly associated with preoperative vision, the duration of silicone oil tamponade, silicone oil removal and retinectomy size. There was also some evidence of association between visual outcome and the number of clock hours of retinal detachment. Final retinal attachment was significantly associated with silicone oil removal and preoperative vision, and final hypotony was significantly associated with silicone oil removal. The incidence of sympathetic ophthalmia in our study was 0.09% (one case). CONCLUSIONS: Good functional outcome is possible following retinectomy surgery despite advanced pathology and often multiple surgical procedures. Retinal redetachment as a result of reproliferation and hypotony appear to be the main reasons for anatomical and functional failure. The clinical features we have identified as good indicators for improved final visual acuity such as shorter tamponade duration, removal of silicone oil, smaller retinectomy size, fewer previous operations and better preoperative vision are surrogate markers of less advanced PVR and should prompt retinal surgeons to consider retinectomy at an earlier stage in the process of PVR development. Clinicians should be aware of the small risk of sympathetic ophthalmia from complex retinal surgery