A rare case of zolendronate infusion complication leading to glaucoma filtration surgery

Zolendronic acid is a nitrogenous biphosphonate commonly used as an intravenous infusion for the management of Paget’s disease, osteoporosis, and hypercalcemia of malignancy. We report a rare and challenging complication of zolendronate infusion: unilateral acute anterior uveitis followed by persistently raised intraocular pressure despite being on four different classes of antiglaucoma medication. The challenge was that the patient required topical steroid to treat her uveitis in the background of known glaucoma with corresponding steroid response. She eventually underwent a left phacotrabeculectomy augmented with 5-fluorouracil. Four weeks postoperatively she developed an encapsulated bleb and underwent needling with 5-fluorouracil. This case highlights the importance of having a high index of suspicion for anterior uveitis in patients with a red and painful eye after initiating biphosphonate therapy. Caution should also be exercised when prescribing biphosponates to glaucoma patients

Visible light affects mitochondrial function and induces neuronal death in retinal cell cultures

AbstractThe aim of this study was to provide “proof of principle” for the hypothesis that light would have a detrimental influence on ganglion cells in certain situations, like in glaucoma, by directly impinging on the many mitochondria in their axons within the globe. In this study primary rat retinal cultures and freshly isolated liver mitochondria were exposed to light (400–760nm; 500–4000lux) as entering the eye. For culture assessment, 3,(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and 4-[3-(-iodophenyl)-2-(4-nitrophenyl)-2H-5-tetzolio]-1,3-benzene disulfonate (WST-1) reduction assays were used to assess cell and mitochondrial viability, respectively. Furthermore, cultures were stained for reactive oxygen species (ROS), DNA breakdown, numbers of GABA-immunoreactive (IR) cells and caspase-3 content to provide information concerning the effect of light on neuronal survival. Uptake of 3H-GABA by autoradiography was also used, to assess the effects of light on the energy status of neurons. Light, in an intensity-dependent and trolox-inhibitable manner, reduced cell viability, affected mitochondrial function, increased the number of TUNEL-positive cells, decreased the numbers of GABA-IR neurons and enhanced labelling for ROS. These effects were all exacerbated by the absence of serum. There was also an increased caspase-3 protein content and a reduction of 3H-GABA uptake in light- compared with dark-treated cultures. These findings support the hypothesis that light can affect mitochondria which could lead to neuronal apoptosis if the energetic status of these neurons is already compromised

Assessing the phenomenology of the Cretan Sea shelf area using coupling modelling techniques

International audienceIn this work the ability of nesting two hydrodynamical models, the high-resolution Cretan Sea shelf model and the lower resolution regional ALERMO model, was investigated. A new database was developed by objectively analysing raw climatological data from the MODB database enriched with in situ measurements collected by the Institute of Marine Biology of Crete. Prior to nesting with the ALERMO model, the Cretan Sea model was integrated using this new hydrological database, in order to investigate the capability of the model setup to describe the phenomenology of the Cretan Sea. Results show that the model can successfully reproduce the complex general circulation characteristics of the area, such as the dipole of a cyclone and an anticyclone, and the flow reversal between winter and summer. As a next step, the shelf-model was one-way nested with the ALERMO model and was integrated on a climatological basis. The evolution of the circulation characteristics of the Cretan Sea was compared, qualitatively and quantitatively, against the results of the regional model, and proved that the nesting between the two models can provide reliable information while overcoming at the same time the computational constraints imposed by high-resolution models

Operational ocean forecasting in the Eastern Mediterranean: implementation and evaluation

The Cyprus Coastal Ocean Forecasting and Observing System (CYCOFOS) has been producing operational flow forecasts of the northeastern Levantine Basin since 2002 and has been substantially improved in 2005. CYCOFOS uses the POM flow model, and recently, within the frame of the MFSTEP project, the flow model was upgraded to use the hourly SKIRON atmospheric forcing, and its resolution was increased from 2.5 km to 1.8 km. The CYCOFOS model is now nested in the ALERMO regional model from the University of Athens, which is nested within the MFS basin model. The Variational Initialization and FOrcing Platform (VIFOP) has been implemented to reduce the numerical transient processes following initialization. Moreover, a five-day forecast is repeated every day, providing more detailed and more accurate information. Forecast results are posted on the web page http://www.oceanography.ucy.ac.cy/cycofos. The new, daily, high-resolution forecasts agree well with the ALERMO regional model. The agreement is better and results more reasonable when VIFOP is used. Active and slave experiments suggest that a four-week active period produces realistic results with more small-scale features. For runs in September 2004, biases with remote sensing sea surface temperature are less than 0.6°C with similar expressions of the flow field present in both. Remotely-observed coastal upwelling south of Cyprus and advection of cool water from the Rhodes Gyre to the southern shores of Cyprus are also modeled. In situ observed hydrographic data from south of Cyprus are similar to the corresponding forecast fields. Both indicate the relatively fresh subsurface Atlantic Water and a near-surface anticyclone south of Cyprus for August/September of 2004 and September 2005. Plans for further model improvement include assimilation of observed XBT temperature profiles, CTD profiles from drifters and gliders, and CT data from the CYCOFOS ocean observatory

The Role of Mitophagy in Glaucomatous Neurodegeneration

settingsOrder Article Reprints Open AccessReview The Role of Mitophagy in Glaucomatous Neurodegeneration by Dimitrios Stavropoulos 1,2,Manjot K. Grewal 3,4,Bledi Petriti 3,5,Kai-Yin Chau 5ORCID,Christopher J. Hammond 6,7,David F. Garway-Heath 3ORCID andGerassimos Lascaratos 1,6,*ORCID 1 Department of Ophthalmology, King’s College Hospital, London SE5 9RS, UK 2 Department of Ophthalmology, 417 Veterans Army Hospital (NIMTS), 11521 Athens, Greece 3 NIHR Biomedical Research Center, Moorfields Eye Hospital and UCL Institute of Ophthalmology, London EC1V 9EL, UK 4 Division of Optometry and Visual Science, School of Health Sciences, City, University of London, London EC1V 0HB, UK 5 Department of Clinical & Movement Neurosciences, UCL Queens Square Institute of Neurology, London NW3 2PF, UK 6 Section of Ophthalmology, School of Life Course Sciences, King’s College London, London SE1 7EH, UK 7 Department of Ophthalmology, St Thomas’ Hospital, London SE1 7EH, UK * Author to whom correspondence should be addressed. Cells 2023, 12(15), 1969; https://doi.org/10.3390/cells12151969 Received: 3 June 2023 / Revised: 15 July 2023 / Accepted: 19 July 2023 / Published: 30 July 2023 (This article belongs to the Special Issue Recent Research on the Role of Mitochondria in Neurodegeneration) Download Browse Figures Review Reports Versions Notes Abstract This review aims to provide a better understanding of the emerging role of mitophagy in glaucomatous neurodegeneration, which is the primary cause of irreversible blindness worldwide. Increasing evidence from genetic and other experimental studies suggests that mitophagy-related genes are implicated in the pathogenesis of glaucoma in various populations. The association between polymorphisms in these genes and increased risk of glaucoma is presented. Reduction in intraocular pressure (IOP) is currently the only modifiable risk factor for glaucoma, while clinical trials highlight the inadequacy of IOP-lowering therapeutic approaches to prevent sight loss in many glaucoma patients. Mitochondrial dysfunction is thought to increase the susceptibility of retinal ganglion cells (RGCs) to other risk factors and is implicated in glaucomatous degeneration. Mitophagy holds a vital role in mitochondrial quality control processes, and the current review explores the mitophagy-related pathways which may be linked to glaucoma and their therapeutic potential

Evaluation of the effect of intravitreal ranibizumab injections in patients with neovascular age related macular degeneration on retinal nerve fiber layer thickness using optical coherence tomography

PURPOSE: To evaluate the effect of repeated intravitreal ranibizumab injections for neovascular age related macular degeneration (nAMD) on the retinal nerve fiber layer (RNFL) thickness using optical coherence tomography. DESIGN: A prospective observational cohort study of patients with nAMD. METHODS: Thirty eyes of 30 patients with nAMD were selected. All patients received three ranibizumab injections and underwent scans using the fast RNFL thickness protocol (Stratus optical coherence tomography) before starting the first injection and 1 month after the third injection. The RNFL thickness measurements prior to the injections and after the third injection were used for the analysis. We also evaluated the effect of the lens status as well as the type of choroidal neovascular membrane on RNFL thickness measurements pre- and post-injection. Pre- and post-injection average and individual quadrant RNFL thickness were measured and statistically analyzed. RESULTS: The mean (± standard deviation) pre-injection RNFL thickness was 90.8±18. The mean (± standard deviation) post-injection RNFL thickness was 91.03±15. The pre- and post-injection values of the mean RNFL thickness were not statistically significant. Likewise, the pre- and post-injection values for RNFL thickness in the different quadrants were not statistically significant. There was no statistical significance for the lens status or the type of choroidal neovascular membrane on the RNFL thickness. CONCLUSION: Repeated ranibizumab injections in nAMD appear to have no harmful effect on the RNFL thickness in the short term, in spite of the proven neurotrophic effect of vascular endothelial growth factor. Nevertheless, the safety profile of ranibizumab injections in nAMD needs to be further evaluated in a large multicenter trial with special emphasis on the long-term effects on the retina and optic nerve

Characterizing, modelling and understanding the climate variability of the deep water formation in the North-Western Mediterranean Sea

Observing, modelling and understanding the climate-scale variability of the deep water formation (DWF) in the North-Western Mediterranean Sea remains today very challenging. In this study, we first characterize the interannual variability of this phenomenon by a thorough reanalysis of observations in order to establish reference time series. These quantitative indicators include 31 observed years for the yearly maximum mixed layer depth over the period 1980–2013 and a detailed multi-indicator description of the period 2007–2013. Then a 1980–2013 hindcast simulation is performed with a fully-coupled regional climate system model including the high-resolution representation of the regional atmosphere, ocean, land-surface and rivers. The simulation reproduces quantitatively well the mean behaviour and the large interannual variability of the DWF phenomenon. The model shows convection deeper than 1000 m in 2/3 of the modelled winters, a mean DWF rate equal to 0.35 Sv with maximum values of 1.7 (resp. 1.6) Sv in 2013 (resp. 2005). Using the model results, the winter-integrated buoyancy loss over the Gulf of Lions is identified as the primary driving factor of the DWF interannual variability and explains, alone, around 50 % of its variance. It is itself explained by the occurrence of few stormy days during winter. At daily scale, the Atlantic ridge weather regime is identified as favourable to strong buoyancy losses and therefore DWF, whereas the positive phase of the North Atlantic oscillation is unfavourable. The driving role of the vertical stratification in autumn, a measure of the water column inhibition to mixing, has also been analyzed. Combining both driving factors allows to explain more than 70 % of the interannual variance of the phenomenon and in particular the occurrence of the five strongest convective years of the model (1981, 1999, 2005, 2009, 2013). The model simulates qualitatively well the trends in the deep waters (warming, saltening, increase in the dense water volume, increase in the bottom water density) despite an underestimation of the salinity and density trends. These deep trends come from a heat and salt accumulation during the 1980s and the 1990s in the surface and intermediate layers of the Gulf of Lions before being transferred stepwise towards the deep layers when very convective years occur in 1999 and later. The salinity increase in the near Atlantic Ocean surface layers seems to be the external forcing that finally leads to these deep trends. In the future, our results may allow to better understand the behaviour of the DWF phenomenon in Mediterranean Sea simulations in hindcast, forecast, reanalysis or future climate change scenario modes. The robustness of the obtained results must be however confirmed in multi-model studies