Interpretation of uniocular and binocular trials of glaucoma medications: an observational case series

<p>Abstract</p> <p>Background</p> <p>To predict the effectiveness of topical glaucoma medications based on initial uniocular and binocular treatment. To test a traditional hypothesis that effectiveness following a uniocular trial is associated with the change in IOP in the initially treated eye minus the change in the initially untreated eye. To determine whether uniocular or binocular treatment trials are superior.</p> <p>Methods</p> <p>Based on a review of medical records, we identified 168 instances in 154 patients with bilateral primary open angle glaucoma of initial uniocular use of a topical glaucoma medication with well-documented intraocular pressure (IOP) readings at baseline (IOP_A), during the trial (IOP_B), and at follow-up (IOP_C). Abstracted data included demographic data, IOP, and medication use. Predictors of the IOP following the trial (IOP_C) in each eye were identified by multivariable linear regression. In 70 cases, the predictive ability of initial uniocular and binocular treatment could be directly compared.</p> <p>Results</p> <p>In a multivariable analysis, the follow-up pressure in the initially treated eye (IOP_1C) was directly correlated with treated eye IOP during initial uniocular use (IOP_1B, p < 0.001). In a multivariable analysis, the follow-up pressure in the initially untreated eye (IOP_2C) was directly correlated with its baseline IOP_2A(p < 0.001), and also tended to be associated with treated IOP_1B(p = 0.07). The multivariable regression coefficient (b) for the IOP change in the initially untreated eye was generally not close to the value of -1 expected by the classic teaching (for eye 1, b = 0.04, p = 0.35; for eye 2, b = 0.07, p = 0.50). In 70 cases, the uniocular and binocular trials predicted a similar fraction of the variance in follow-up IOP_1C(r²= 0.56 and 0.57, respectively) and IOP_2C(r²= 0.39 and 0.38, respectively).</p> <p>Conclusion</p> <p>1) For uniocular trials, the IOP change in the untreated eye should not be subtracted from that in the treated eye. 2) Uniocular and binocular trials have similar predictive value when interpreted correctly. Either may be selected based on clinical circumstances.</p

Cochlin, Intraocular Pressure Regulation and Mechanosensing

Fluid shear modulates many biological properties. How shear mechanosensing occurs in the extracellular matrix (ECM) and is transduced into cytoskeletal change remains unknown. Cochlin is an ECM protein of unknown function. Our investigation using a comprehensive spectrum of cutting-edge techniques has resulted in following major findings: (1) over-expression and down-regulation of cochlin increase and decrease intraocular pressure (IOP), respectively. The overexpression was achieved in DBA/2J-Gpnmb+/SjJ using lentiviral vectors, down-regulation was achieved in glaucomatous DBA/2J mice using targeted disruption (cochlin-null mice) and also using lentiviral vector mediated shRNA against cochlin coding region; (2) reintroduction of cochlin in cochlin-null mice increases IOP; (3) injection of exogenous cochlin also increased IOP; (4) increasing perfusion rates increased cochlin multimerization, which reduced the rate of cochlin proteolysis by trypsin and proteinase K; The cochlin multimerization in response to shear stress suggests its potential mechanosensing. Taken together with previous studies, we show cochlin is involved in regulation of intraocular pressure in DBA/2J potentially through mechanosensing of the shear stress

Molecular mechanisms of severe acute respiratory syndrome (SARS)

Severe acute respiratory syndrome (SARS) is a new infectious disease caused by a novel coronavirus that leads to deleterious pulmonary pathological features. Due to its high morbidity and mortality and widespread occurrence, SARS has evolved as an important respiratory disease which may be encountered everywhere in the world. The virus was identified as the causative agent of SARS due to the efforts of a WHO-led laboratory network. The potential mutability of the SARS-CoV genome may lead to new SARS outbreaks and several regions of the viral genomes open reading frames have been identified which may contribute to the severe virulence of the virus. With regard to the pathogenesis of SARS, several mechanisms involving both direct effects on target cells and indirect effects via the immune system may exist. Vaccination would offer the most attractive approach to prevent new epidemics of SARS, but the development of vaccines is difficult due to missing data on the role of immune system-virus interactions and the potential mutability of the virus. Even in a situation of no new infections, SARS remains a major health hazard, as new epidemics may arise. Therefore, further experimental and clinical research is required to control the disease

Author Correction: Cross-ancestry genome-wide association analysis of corneal thickness strengthens link between complex and Mendelian eye diseases

Emmanuelle Souzeau, who contributed to analysis of data, was inadvertently omitted from the author list in the originally published version of this Article. This has now been corrected in both the PDF and HTML versions of the Article

A generalised porous medium approach to study thermo-fluid dynamics in human eyes

The present work describes the application of the generalised porous medium model to study heat and fluid flow in healthy and glaucomatous eyes of different subject specimens, considering the presence of ocular cavities and porous tissues. The 2D computational model, implemented into the open-source software OpenFOAM, has been verified against benchmark data for mixed convection in domains partially filled with a porous medium. The verified model has been employed to simulate the thermo-fluid dynamic phenomena occurring in the anterior section of four patient-specific human eyes, considering the presence of anterior chamber (AC), trabecular meshwork (TM), Schlemm’s canal (SC), and collector channels (CC). The computational domains of the eye are extracted from tomographic images. The dependence of TM porosity and permeability on intraocular pressure (IOP) has been analysed in detail, and the differences between healthy and glaucomatous eye conditions have been highlighted, proving that the different physiological conditions of patients have a significant influence on the thermo-fluid dynamic phenomena. The influence of different eye positions (supine and standing) on thermo-fluid dynamic variables has been also investigated: results are presented in terms of velocity, pressure, temperature, friction coefficient and local Nusselt number. The results clearly indicate that porosity and permeability of TM are two important parameters that affect eye pressure distribution

Understanding charge transport in donor/acceptor blends from large-scale device simulations based on experimental film morphologies

Bulk-heterojunction organic photovoltaic (OPV) devices consist of active layers made of electron donor/acceptor blends. Understanding the impact of the blend morphologies on the optoelectronic processes occurring in OPVs is of crucial importance for a complete description of the device physics and the achievement of higher device efficiencies. However, high-resolution morphology data are scarce and theoretical methodologies with the appropriate level of details and affordable computational costs are underdeveloped. As a result, previous device modeling often had to rely on artificially generated blend morphologies, which do not represent those in actual devices. Here, by considering three-dimensional donor/acceptor blend morphologies recently determined via electron tomography, we have established an original approach that allows us to perform device-scale simulations of charge transport in actual blend morphologies. The current characteristics, carrier distributions, and internal current pathways and densities are determined and compared to those based on the artificial morphologies often used in OPV-related studies

Understanding charge transport in donor/acceptor blends from large-scale device simulations based on experimental film morphologies

Bulk-heterojunction organic photovoltaic (OPV) devices consist of active layers made of electron donor/acceptor blends. Understanding the impact of the blend morphologies on the optoelectronic processes occurring in OPVs is of crucial importance for a complete description of the device physics and the achievement of higher device efficiencies. However, high-resolution morphology data are scarce and theoretical methodologies with the appropriate level of details and affordable computational costs are underdeveloped. As a result, previous device modeling often had to rely on artificially generated blend morphologies, which do not represent those in actual devices. Here, by considering three-dimensional donor/acceptor blend morphologies recently determined via electron tomography, we have established an original approach that allows us to perform device-scale simulations of charge transport in actual blend morphologies. The current characteristics, carrier distributions, and internal current pathways and densities are determined and compared to those based on the artificial morphologies often used in OPV-related studies