Moorfields Eye Hospital

About: Moorfields Eye Hospital is a healthcare organization based out in London, United Kingdom. It is known for research contribution in the topics: Visual acuity & Glaucoma. The organization has 3721 authors who have published 6790 publications receiving 246004 citations.

Genome-wide association study identifies susceptibility loci for open angle glaucoma at TMCO1 and CDKN2B-AS1

Abstract: We report a genome-wide association study for open-angle glaucoma (OAG) blindness using a discovery cohort of 590 individuals with severe visual field loss (cases) and 3,956 controls. We identified associated loci at TMCO1 (rs4656461[G] odds ratio (OR) = 1.68, P = 6.1 × 10(-10)) and CDKN2B-AS1 (rs4977756[A] OR = 1.50, P = 4.7 × 10(-9)). We replicated these associations in an independent cohort of cases with advanced OAG (rs4656461 P = 0.010; rs4977756 P = 0.042) and two additional cohorts of less severe OAG (rs4656461 combined discovery and replication P = 6.00 × 10(-14), OR = 1.51, 95% CI 1.35-1.68; rs4977756 combined P = 1.35 × 10(-14), OR = 1.39, 95% CI 1.28-1.51). We show retinal expression of genes at both loci in human ocular tissues. We also show that CDKN2A and CDKN2B are upregulated in the retina of a rat model of glaucoma.

LRG1 promotes angiogenesis by modulating endothelial TGF-β signalling

Abstract: Aberrant neovascularization contributes to diseases such as cancer, blindness and atherosclerosis, and is the consequence of inappropriate angiogenic signalling. Although many regulators of pathogenic angiogenesis have been identified, our understanding of this process is incomplete. Here we explore the transcriptome of retinal microvessels isolated from mouse models of retinal disease that exhibit vascular pathology, and uncover an upregulated gene, leucine-rich alpha-2-glycoprotein 1 (Lrg1), of previously unknown function. We show that in the presence of transforming growth factor-β1 (TGF-β1), LRG1 is mitogenic to endothelial cells and promotes angiogenesis. Mice lacking Lrg1 develop a mild retinal vascular phenotype but exhibit a significant reduction in pathological ocular angiogenesis. LRG1 binds directly to the TGF-β accessory receptor endoglin, which, in the presence of TGF-β1, results in promotion of the pro-angiogenic Smad1/5/8 signalling pathway. LRG1 antibody blockade inhibits this switch and attenuates angiogenesis. These studies reveal a new regulator of angiogenesis that mediates its effect by modulating TGF-β signalling. LRG1 is identified as a new regulator of TGF-β signalling that promotes angiogenesis via a TβRII–ALK1–ENG–Smad1/5/8 signalling pathway; antibody-mediated inhibition of LRG1 reduces pathogenic neovascularization in a mouse model of retinal injury. Defective angiogenesis is a common feature in many diseases including age-related macular degeneration, atherosclerosis, rheumatoid arthritis and cancer. Here John Greenwood and colleagues identify a novel angiogenic glycoprotein of previously unknown function — leucine-rich-alpha-2-glycoprotein 1 (LRG1) — that exerts its effect through modifying TGF-β signalling. LRG1, upregulated in vitreous samples from humans with proliferative diabetic retinopathy, activates an angiogenic switch by binding to the receptor endoglin and promoting pro-angiogenic TGF-β signalling. Antibody-mediated inhibition of LRG1 reduces pathogenic neovascularization in a mouse model of retinal injury, which suggests that LRG1 is a possible therapeutic target for controlling pathological angiogenesis in ocular disease.

Safety and efficacy of intravitreal triamcinolone for cystoid macular oedema in uveitis.

Abstract: Purpose: To report the safety and efficacy of intravitreal triamcinolone in the treatment of inflammatory cystoid macular oedema (CMO) in six patients who were resistant to other forms of therapy. Methods: An open-label unmasked prospective non- randomized pilot study of six patients with idiopathic uveitis and visually significant macular oedema, resistant to periocular and/or systemic corticosteroid treatment, was carried out. Baseline examination and investigations were performed, including fundus fluorescein angiography, and the patients were given a single intravitreal injection of triamcinolone (4 mg/0.1 mL). The primary outcome measure was angiographic resolution of CMO. Patients were reviewed at intervals of 2–4 weeks for 12 months. Results: A single intravitreal injection of triamcinolone induced clinical and angiographic resolution of inflammatory macular oedema in all patients for varying periods of time up to 6 months. Five patients experienced increased intraocular pressure to 30 mmHg or greater which required treatment. Two patients developed posterior subcapsular cataract. Conclusion: One injection of intravitreal triamcinolone was an effective short-term treatment for resistant CMO in uveitis. As with steroids given by other routes, raised intraocular pressure and cataract may occur. As it was so effective in these eyes with resistant CMO, a larger study is warranted to evaluate this form of therapy.

The epidemiology of rhegmatogenous retinal detachment: geographical variation and clinical associations.

Abstract: Aims/Background Rhegmatogenous retinal detachment (RRD) is a potentially blinding condition. Obtaining an accurate estimate of RRD incidence in the population is essential in understanding the healthcare burden related to this disorder. Methods A systematic review of all population-based epidemiology studies of RRD published between January 1970 and January 2009 from Medline database searches was performed. Results RRD incidence demonstrates significant geographical variation and its incidence has been reported to be between 6.3 and 17.9 per 100 000 population. For studies with a sample size >300 the median annual incidence per 100 000 population was 10.5 (IQR 8.1–13.2) and the mean proportion of bilateral RRD was 7.26%. Overall, the mean prevalence of lattice degeneration was 45.7±20.3% and myopia was 47.28±12.59%. Conclusions Estimates of RRD incidence have varied threefold, but inclusion criteria and other design features have differed across studies making direct comparisons difficult. The overall incidence of RRD is not yet well established: more incidence studies of adequate methodology are needed to explore temporal changes in incidence. RRD incidence varies with ethnicity and is strongly associated with increasing age, myopia and certain vitreo-retinal degenerations. Due to changes in cataract surgery trends, the proportion of pseudophakic RRD presenting to specialised centres appears to be increasing.