Intraocular pressure reduction in glaucoma: Does every mmHg count?

The reduction of intraocular pressure is currently the only known modifiable risk factor for the treatment of Glaucoma, which is the leading cause of irreversible worldwide blindness. This concise review discusses the evidence underpinning the reduction of intraocular pressure in the treatment of glaucoma, the role of target intraocular pressure in clinical practice and appraises clinical data supporting the concept that every mmHg of intraocular pressure reduction is important in reducing the risk of developing glaucoma and the progression of existing disease. Every mmHg in IOP reduction is important, with evidence showing an impact on both functional and structural progression but does not however explain all glaucoma risk

Geometric Mechanics of Contact-Switching Systems

Discrete and periodic contact switching is a key characteristic of steady state legged locomotion. This paper introduces a framework for modeling and analyzing this contact-switching behavior through the framework of geometric mechanics on a toy robot model that can make continuous limb swings and discrete contact switches. The kinematics of this model forms a hybrid shape space and by extending the generalized Stokes' theorem to compute discrete curvature functions called stratified panels, we determine average locomotion generated by gaits spanning multiple contact modes. Using this tool, we also demonstrate the ability to optimize gaits based on system's locomotion constraints and perform gait reduction on a complex gait spanning multiple contact modes to highlight the scalability to multilegged systems.Comment: 6 pages, 7 figures, and link to associated video: https://drive.google.com/file/d/12Sgl0R1oDLDWRrqlwwAt3JR2Gc3rEB4T/view?usp=sharin

Assessment of VR Technology and its Applications to Engineering Problems

Virtual reality applications are making valuable contributions to the field of product realization. This paper presents an assessment of the hardware and software capabilities of VR technology needed to support a meaningful integration of VR applications in the product life cycle analysis. Several examples of VR applications for the various stages of the product life cycle engineering are presented as case studies. These case studies describe research results, fielded systems, technical issues, and implementation issues in the areas of virtual design, virtual manufacturing, virtual assembly, engineering analysis, visualization of analysis results, and collaborative virtual environments. Current issues and problems related to the creation, use, and implementation of virtual environments for engineering design, analysis, and manufacturing are also discussed

Stem Cell Based Therapies for Glaucoma

Glaucoma remains one of the leading causes of worldwide blindness. In England and Wales glaucoma is a major or contributory factor for 12-14% of all registrations for blindness and partial sight, second only to macular degeneration (Bunce et al., 2010). The worldwide burden is more significant, with glaucoma being the second leading cause of global blindness after cataract (Resnikoff et al., 2004). It has been estimated that 60.5 million people worldwide would be affected by glaucoma by 2010, with the figure expected to rise to 80 million by 2020 (Quigley and Broman, 2006). Current treatments for glaucoma comprise the lowering of intraocular pressure by eye drops, laser procedures or drainage surgery. However, as implied by the statistics above, many patients experience significant visual loss due to degeneration of retinal ganglion cells (RGCs) despite the advances in the treatments currently available. The need for novel therapies exists for such patients, in particular those with end stage glaucoma, where maintenance of a small number of surviving RGCs may yet permit a reasonable quality of life (Much et al., 2008). Stem cell therapies developed in the laboratory and translated to clinical practice provide an exciting and realistic hope for those affected by degenerative retinal diseases including glaucoma. This chapter will discuss three mechanisms by which stem cell therapies may potentially offer hope to patients with glaucoma, namely local retinal ganglion cell replacement, retina and optic nerve regeneration and stem cell mediated neuroprotection

Validation of the RCOphth and UKEGS glaucoma risk stratification tool 'GLAUC-STRAT-fast'

BACKGROUND/AIMS: The aim of this study was to validate the Glaucoma Risk Stratification Tool (GLAUC-STRAT-fast) currently recommended by the Royal College of Ophthalmologists for the risk stratification of patients with glaucoma in the UK National Health Service Hospital Eye Service. METHODS: GLAUC-STRAT fast was applied to the LiGHT trial participants by risk-stratifying the worse eye of each patient at baseline and after 3 years of treatment. Metrics of disease severity or treatment intensity used for the validation were: increased number of monitoring visits or treatment escalations; needing a trabeculectomy; a reduction of >2 dB in visual field mean deviation (VF MD) during the monitoring period; identification of rapid VF loss on total (TD) and/or pattern deviation (PD). The proportion of eyes within each baseline stratum for each of the above markers was compared against the other strata, using a χ2 test for proportions. RESULTS: There was an association between the baseline stratification and the number of treatment escalations needed to maintain the eye-specific target intraocular pressure (p=0.001), the number of visits needed throughout the 3-year follow-up period (p=0.001), the need for trabeculectomy (p<0.001) and absolute loss of MD over the course of the monitoring period (p<0.001). The rate of VF progression was not associated with baseline risk stratification for TD or PD progression (p≥0.007, with Bonferroni correction). CONCLUSION: The GLAUC-STRAT fast tool is a useful tool for risk stratifying eyes with ocular hypertension or open angle glaucoma. Further research is needed to confirm and validate its applicability to more advanced glaucomas and generalisability to clinical use. TRIAL REGISTRATION NUMBER: The LiGHT trial is registered at controlled-trials.com (ISRCTN32038223)

Cell-Based Therapies for Glaucoma

Glaucomatous optic neuropathy (GON) is the major cause of irreversible visual loss worldwide and can result from a range of disease etiologies. The defining features of GON are retinal ganglion cell (RGC) degeneration and characteristic cupping of the optic nerve head (ONH) due to tissue remodeling, while intraocular pressure remains the only modifiable GON risk factor currently targeted by approved clinical treatment strategies. Efforts to understand the mechanisms that allow species such as the zebrafish to regenerate their retinal cells have greatly increased our understanding of regenerative signaling pathways. However, proper integration within the retina and projection to the brain by the newly regenerated neuronal cells remain major hurdles. Meanwhile, a range of methods for in vitro differentiation have been developed to derive retinal cells from a variety of cell sources, including embryonic and induced pluripotent stem cells. More recently, there has been growing interest in the implantation of glial cells as well as cell-derived products, including neurotrophins, microRNA, and extracellular vesicles, to provide functional support to vulnerable structures such as RGC axons and the ONH. These approaches offer the advantage of not relying upon the replacement of degenerated cells and potentially targeting earlier stages of disease pathogenesis. In order to translate these techniques into clinical practice, appropriate cell sourcing, robust differentiation protocols, and accurate implantation methods are crucial to the success of cell-based therapy in glaucoma. Translational Relevance: Cell-based therapies for glaucoma currently under active development include the induction of endogenous regeneration, implantation of exogenously derived retinal cells, and utilization of cell-derived products to provide functional support

Optic Nerve Head Gene Transcription Sequelae to a Single Elevated IOP Exposure Provides Insights Into Known Responses to Chronically Elevated IOP

Purpose: To clarify the optic nerve head (ONH) gene expression responses associated with a single, axon-damaging exposure to elevated IOP in relation to the composite cellular events previously identified in models of chronically elevated IOP. Methods: Anesthetized rats were exposed unilaterally to an 8-hour pulse-train controlled elevation of IOP (PT-CEI) at 60 mm Hg, while others received normotensive CEI at 20 mm Hg. ONH RNA was harvested at 0 hours and 1, 2, 3, 7, and 10 days after either CEI and from naïve animals. RNA sequencing was performed to analyze ONH gene expression. DAVID Bioinformatics tools were used to identify significant functional annotation clusters. Gene function was compared between PT-CEI and two models of chronic ocular hypertension from the literature. Results: The number of significantly changed genes peaked immediately (n = 1354) after PT-CEI (0 hours). This was followed by a lull (point) at 1 and 2 days after PT-CEI. Gene activity increased again at 3 days (136 genes) and persisted at 7 (78 genes) and 10 (339 genes) days. Significant gene functional categories included an immediate upregulation of Defense Response at 0 hours, followed by upregulation in Cell Cycle, a reduction in Axonal-related genes at 3 to 10 days, and upregulation of Immune Response–related genes at 10 days following PT-CEI. The most commonly upregulated gene expression across our PT-CEI study and two chronic models of ocular hypertension were cell cycle related. Conclusions: The PT-CEI model places in sequence ONH gene expression responses previously reported in models with chronically elevated IOP and may provide insights into their role in optic nerve damage

Concomitant primary breast carcinoma and primary choroidal melanoma: a case report

<p>Abstract</p> <p>Introduction</p> <p>Choroidal melanoma and choroidal metastasis are distinct pathological entities with very different treatments and prognoses. They may be difficult to distinguish to the untrained observer.</p> <p>Case presentation</p> <p>A case of concomitant choroidal melanoma in a woman with primary breast carcinoma is described. The choroidal lesion was thought initially to be a metastasis, and treated with external beam radiotherapy. The tumour did not regress but remained stable in size for a period of three years. Following referral to an ophthalmologist, the diagnosis was revised after re-evaluation of the clinical, ultrasonographic and angiographic findings.</p> <p>Conclusion</p> <p>Although metastases are the most common ocular tumour, a differential diagnosis of a concurrent primary ocular malignancy should always be considered, even in patients with known malignant disease. Thorough ophthalmic evaluation is important, as multiple primary malignancies may occur concomitantly. The prognostic and therapeutic implications of accurate diagnosis by an ophthalmologist are of profound significance to affected patients and their families.</p

Midlife diagnosis of Refsum Disease in siblings with Retinitis Pigmentosa – the footprint is the clue: a case report

<p>Abstract</p> <p>Introduction</p> <p>Refsum disease is a potentially lethal and disabling condition associated with retinitis pigmentosa in which early treatment can prevent some of the systemic manifestations.</p> <p>Case presentation</p> <p>We present the cases of two brothers with a diagnosis of retinitis pigmentosa from childhood in whom Refsum disease was subsequently diagnosed midlife, after routine enquiry into hand and feet abnormalities. Subsequent treatment through dietary modification stabilised visual impairment and has prevented development of neurological complications to date.</p> <p>Conclusion</p> <p>It is therefore important to consider the diagnosis of Refsum disease in any patient with autosomal recessive or simplex retinitis pigmentosa, and to enquire about the presence of "unusual" feet or hands in such patients.</p