Clinical efficacy of eplerenone versus placebo for central serous chorioretinopathy:study protocol for the VICI randomised controlled trial

Chronic central serous chorioretinopathy (CSCR) is poorly understood. Fluid accumulates in the subretinal space and retinal pigment epitheliopathy and neurosensory atrophy may develop. Permanent vision loss occurs in approximately one third of cases. There are no effective treatments for CSCR. Recent studies have shown the mineralocorticoid receptor antagonist, eplerenone, to be effective in resolving subretinal fluid and improving visual acuity. This trial aims to compare the safety and efficacy of eplerenone in patients with CSCR in a double-masked randomised placebo-controlled trial. Patients are randomised 1:1 to receive eplerenone with usual care or placebo with usual care for 12 months; 25 mg per day for 1 week, then 50 mg per day up to 12 months (unless discontinued for safety or resolution of CSCR). Key eligibility criteria are: age 18-60 years, one eye with CSCR for ≥4 months duration, best-corrected visual acuity (BCVA) >53 and <86 letters and no previous treatment. The primary outcome is BCVA at 12 months. Secondary outcomes include resolution of subretinal fluid, development of macular atrophy, subfoveal choroidal thickness, changes in low luminance visual acuity, health-related quality of life and safety. Recruitment is complete but was slower than expected. We maintained the eligibility criteria to ensure participants had 'true' CSCR and recruited additional centres. Effective distribution of the investigational medicinal product (IMP) was achieved by implementing a database to manage ordering and accountability of IMP packs. The results will provide adequately powered evidence to inform clinical decisions about using eplerenone to treat patients with CSCR

The immunopathology of human recent-onset type 1 diabetes

EThOS - Electronic Theses Online ServiceGBUnited Kingdo

The immunopathology of human recent-onset type 1 diabetes

EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Downregulation of proliferation does not affect the secretory function of transformed beta-cell lines regardless of their anatomical configuration

AIMS AND OBJECTIVES: Proliferation in transformed β-cell lines is high compared to primary islet cells and is accompanied by reduced insulin content and release. Our aim was to determine whether experimental reduction of proliferation restores the cells to a more authentic β-cell phenotype in terms of secretory function and to investigate the potential beneficial effect of their configuration as islet-like structures.RESULTS: Mitosis inhibitor mitomycin c treatment neither altered the rate of proliferation nor improved the secretory responses of MIN6 monolayer cells. The proliferative rate of MIN6 cells was not affected by pseudoislet formation, but in contrast to monolayer cells, pseudoislets responded to 20 mM glucose with a 2.6-fold increase in insulin secretion. MMC reduced proliferation in MIN6 pseudoislets, but did not further improve their secretory responsiveness. Withdrawal of doxycycline resulted in complete growth-arrest in R7T1 cells, but monolayer and pseudoislet R7T1 cells were unresponsive to glucose and remained so upon growth-arrest although insulin content was increased in growth-arrested pseudoislets.METHODS: MIN6 monolayer and pseudoislet cells were treated with MMC whereas growth-arrest was induced in R7T1 monolayer and pseudoislet cells by withdrawal of doxycycline. Proliferation rates were determined by immunocytochemical measurements of BrdU incorporation and insulin secretion was assessed by radioimmunoassay.CONCLUSIONS: Secretory function of transformed β-cells is not influenced by experimental reduction of proliferation, but can be modulated by enhanced cell-cell contact within islet-like structures. These results have implications for future studies of islet cell redifferentiation and for the generation of islet-like material for transplantation therapy in Type 1 diabetes.</p

American Academy of Optometry Microbial Keratitis Think Tank

SIGNIFICANCE. Think Tank 2019 affirmed that the rate of infection associated with contact lenses has not changed in several decades. Also, there is a trend towards more serious infections associated with acanthamoeba and fungi. The growing use of contact lenses in children demands our attention with surveillance and case control studies. PURPOSE. The American Academy of Optometry (AAO) gathered researchers and key opinion leaders from around the world to discuss contact lens associated microbial keratitis at the 2019 AAO Annual Meeting. METHODS. Experts presented within four sessions. Session 1 covered the epidemiology of microbial keratitis, pathogenesis of Pseudomonas aeruginosa, and the role of lens care systems and storage cases in corneal disease. Session 2 covered non-bacterial forms of keratitis in contact lens wearers. Session 3 covered future needs, challenges and research questions in relation to microbial keratitis in youth and myopia control, microbiome, antimicrobial surfaces, and genetic susceptibility. Session 4 covered compliance and communication imperatives. RESULTS. The absolute rate of microbial keratitis has remained very consistent over 3 decades despite new technologies, and extended wear significantly increases the risk. Improved oxygen delivery afforded by silicone hydrogel lenses has not impacted the rates, and while the introduction of daily disposable lenses has minimized the risk for severe disease, there is no consistent evidence that they have altered the overall rate of microbial keratitis. Overnight orthokeratology lenses may increase risk for microbial keratitis, especially secondary to Acanthamoeba, in children. Compliance remains a concern and a significant risk factor for disease. New insights into host microbiome and genetic susceptibility may uncover new theories. More studies such as case-control designs suited for rare diseases, and registries are needed. CONCLUSIONS. The first annual AAO Think Tank acknowledged that the risk of microbial keratitis has not decreased over decades, despite innovation. Important questions and research directions remain

Germinal centre frequency is decreased in pancreatic lymph nodes from individuals with recent-onset type 1 diabetes.

Pancreatic lymph nodes (PLNs) are critical sites for the initial interaction between islet autoantigens and autoreactive lymphocytes, but the histology of PLNs in tissue from individuals with type 1 diabetes has not been analysed in detail. The aim of this study was to examine PLN tissue sections from healthy donors compared with those at risk of, or with recent-onset and longer-duration type 1 diabetes.This article is freely available via Open Access. Click on the Additional Link above to access the full-text