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Background: Complicated cataract surgery is the main cause of secondary lens implantation surgery. Several approaches have been introduced to face those circumstances. As it concerns scleral-fixated IOLs for the posterior chamber, many types of IOL can be implanted. The aim of article is to review the single piece sutureless scleral fixation Carlevale lens; Methods: Narrative review; Results: Several works described as safe the IOL implantation utilizing the handshake approach, without tactile manipulation, which allows for self-centration and lens firm fixation in uncomplicated surgery. This allows to reduce high order aberration such as astigmatism and coma, with a very good postoperative BCVA Conclusions: Carlevale lens is one of the best option to manage insufficient capsular support.

Purpose The aim this study is to determine anterior chamber parameters variations induced by PreserFlo MicroShunt implantation, in the early post-operative days. Methods This is a prospective observational study on 48 eyes undergoing PreserFlo MicroShunt implantation alone (n = 30) or combined with phacoemulsification (n = 18). Anterior chamber depth (ACD) and volume (ACV), central corneal thickness (CCT) and total corneal astigmatism (TCA) were evaluated pre-operatively, post-operatively at day-1 and at 1 week with the Pentacam tomography. Results Intraocular pressure decreased significantly from 20.9 ± 4.0 to 8.0 ± 2.8 mmHg (p p = 0.0001) at day-1 and week-1, respectively. TCA varied significantly from baseline (1.5 ± 1.2 D) to both day 1 follow up (2.7 ± 1.9 D, p = 0.0003) and week 1 follow up (2.2 ± 1.6 D, p = 0.02). Nevertheless, only K1 showed a transient flattening at day 1, while K2 value didn’t show any statistical variation in the early post-operative period. CCT value rose significantly at day 1 (547 ± 49 vs. 529 ± 32 µm at baseline, p = 0.04), but then returned toward pre-operative values at week 1 (537 ± 39 µm, p = 0.57). In contrast, ACD values changed insignificantly from 3.3 ± 0.9 to 3.7 ± 1.0 mm at day 1 (p = 0.21), and then stabilized at 3.4 ± 0.9 mm (p = 0.82) at week 1 follow up. ACV changed from 150.0 ± 36.2 to 159.5 ± 42.1 mm3 at day 1 (p = 0.58), and successively to 153.9 ± 37.9 mm3 at week 1 follow up (p = 0.96). The subgroup analysis in eyes undergoing standalone PreserFlo implantation didn’t show significant changes in both ACD and ACV. Conclusion PreserFlo implantation minimizes the anterior chamber modifications generated by traditional filtering surgery, inducing low and transient corneal and biometric changes only in the very early postoperative period and insignificant changes to ACD and ACV, label of its safety and minimal invasiveness.

Introduction To explore the early efficacy and safety of treatment with intravitreal injections of brolucizumab in patients presenting neovascular age-related macular degeneration (nAMD) in a real-world setting. Methods This retrospective study included 194 eyes of 180 patients with nAMD treated with standard 6-mg intravitreal injections (IVTs) of brolucizumab in our clinic between 11 March 2021 and 15 June 2022. Both treatment-naive (33 eyes) and switch-therapy patients (161 eyes) were included in the study. Best corrected visual acuity (BCVA), central subfield thickness (CST), retinal fluid distribution (classified as intraretinal, IRF; subretinal, SRF; under the pigmented epithelium, sRPEF), treatment intervals and adverse event rates were collected for analysis. Results Average follow-up time was 37.2±16.6 weeks. Mean baseline BCVA were 38.1±4.5 and 41.9±6.7 letters in the treatment-naive and switch-therapy groups, with a final gain of 16.0±4.9 (p

Purpose To report the case of a patient who presented with a peripapillary retinal detachment caused by pathological myopia. Observations A 73-year-old female with a clinical history of high myopia was admitted to our ophthalmic department complaining of vision loss in her right eye. Her best-corrected visual acuity was 20/25 in the right eye and 20/400 in the left eye. The refractive error was −9.00 D in both eyes. The anterior segment and pupillary reflex were normal. Dilated fundus examination revealed myopic retinopathy in both eyes and a yellow peripapillary lesion, distinct from the myopic conus and encircling almost the whole optic disc, in her right eye. The left eye displayed macular atrophy with macular pigmentation due to a previous myopic choroidal neovascularization. Optical coherence tomography showed a localized retinal detachment in the peripapillary area, adjacent to the inferior edge of the optic disc, giving a strange “seagull wings” appearance. Conclusions and Importance In case of peripapillary neuroepithelial detachment the presence of PDPM in high myopic patients should always be excluded. Further research is due in order to better understand this clinical entity's pathogenesis and prognosis.

Fabry disease (FD) is an X-linked lysosomal storage disorder, causing Gb-3 (globotriaosylceramide) buildup in cellular lysosomes throughout the body, in particular in blood vessel walls, neuronal cells, and smooth muscle. The gradual accumulation of this glycosphingolipid in numerous eye tissues causes conjunctival vascular abnormalities, corneal epithelial opacities (cornea verticillata), lens opacities, and retinal vascular abnormalities. Although a severe vision impairment is rare, these abnormalities are diagnostic indicators and prognostics for severity. Cornea verticillata is the most common ophthalmic feature in both hemizygous men and heterozygous females. Vessel tortuosity has been linked to a faster disease progression and may be useful in predicting systemic involvement. New technologies such as optical coherence tomography angiography (OCTA) are useful for monitoring retinal microvasculature alterations in FD patients. Along with OCTA, corneal topographic analysis, confocal microscopy, and electro-functional examinations, contributed to the recognition of ocular abnormalities and have been correlated with systemic involvement. We offer an update regarding FD ocular manifestations, focusing on findings derived from the most recent imaging modalities, to optimize the management of this pathology.

Background To discuss the efficacy of an inferior implant of XEN 63 gel stent in a patient with refractory glaucoma after trabeculectomy failure and vitreoretinal surgery with silicone oil tamponade. Case Description We report the case of a 73-year-old man with a history of refractory open glaucoma with trabeculectomy failure. He experienced recurrent retinal detachments with silicone oil tamponade, with uncontrolled intra-ocular pressure (IOP) after silicone oil removal. Due to the presence of oil emulsion in the anterior chamber, the chosen location for XEN 63 implantation was the infero-temporal quadrant. Mild hyphema and vitreous hemorrhage were seen post-operatively, but were self-limiting. At week 1, the intraocular pressure was 8 mmHg with a well-formed bleb seen in anterior segment optical coherence tomography (AS-OCT). At 6 month follow up, the patient maintained a IOP of 12 mmHg without topical hypotensive drugs. Slit lamp examination revealed a widespread, developed bleb with no signs of inflammation. Conclusion In this case of refractory glaucoma in a vitrectomized eye with previous oil tamponade, the inferior placement of the XEN 63 gel stent delivered an adequate intraocular pressure even at 6-months follow up, with a diffuse functional infero-nasal bleb seen with AS-OCT.

In tissues as diverse as amphibian skin and the human airway, the cilia that propel fluid are grouped in sparsely distributed multiciliated cells (MCCs). We investigate fluid transport in this "mosaic" architecture, with emphasis on the trade-offs that may have been responsible for its evolutionary selection. Live imaging of MCCs in embryos of the frog $Xenopus~laevis$ shows that cilia bundles behave as active vortices that produce a flow field accurately represented by a local force applied to the fluid. A coarse-grained model that self-consistently couples bundles to the ambient flow reveals that hydrodynamic interactions between MCCs limit their rate of work so that when the system size is large compared to a single MCC, they best shear the tissue at low area coverage, a result that mirrors findings for other sparse distributions such as cell receptors and leaf stomata., 5 pages, 4 figures; Supplemental Material (4 pages, 4 figures) included

Summary Centrioles are cylindrical assemblies whose peripheral microtubule array displays a 9-fold rotational symmetry that is established by the scaffolding protein SAS6. Centriole symmetry can be broken by centriole-associated structures, such as the striated fibers in Chlamydomonas that are important for ciliary function. The conserved protein CCDC61/VFL3 is involved in this process, but its exact role is unclear. Here, we show that CCDC61 is a paralog of SAS6. Crystal structures of CCDC61 demonstrate that it contains two homodimerization interfaces that are similar to those found in SAS6, but result in the formation of linear filaments rather than rings. Furthermore, we show that CCDC61 binds microtubules and that residues involved in CCDC61 microtubule binding are important for ciliary function in Chlamydomonas. Together, our findings suggest that CCDC61 and SAS6 functionally diverged from a common ancestor while retaining the ability to scaffold the assembly of basal body-associated structures or centrioles, respectively., Graphical Abstract, Highlights • CCDC61 is a paralog of SAS6, XRCC4, XLF, and PAXX • CCDC61 can form protofilaments with a 3-fold screw axis in vitro • CCDC61 binds to microtubules mainly via its coiled-coil domain • Microtubule binding of CCDC61 is important for its function in Chlamydomonas, Members of the XRCC4 superfamily of proteins have scaffolding functions in DNA repair or centriole formation. Ochi et al. describe the centrosomal protein CCDC61 as a member of this superfamily. CCDC61 oligomerizes and also binds to microtubules which plays a role in establishing accessory structures of centrioles in Chlamydomonas.

Summary Blood flow modulates endothelial cell (EC) response during angiogenesis. Shear stress is known to control gene expression related to the endothelial-mesenchymal transition and endothelial-hematopoietic transition. However, the impact of blood flow on the cellular processes associated with EC extrusion is less well understood. To address this question, we dynamically record EC movements and use 3D quantitative methods to segregate the contributions of various cellular processes to the cellular trajectories in the zebrafish dorsal aorta. We find that ECs spread toward the cell extrusion area following the tissue deformation direction dictated by flow-derived mechanical forces. Cell extrusion increases when blood flow is impaired. Similarly, the mechanosensor polycystic kidney disease 2 (pkd2) limits cell extrusion, suggesting that ECs actively sense mechanical forces in the process. These findings identify pkd2 and flow as critical regulators of EC extrusion and suggest that mechanical forces coordinate this process by maintaining ECs within the endothelium.

Myocardial contractility and blood flow provide essential mechanical cues for the morphogenesis of the heart. In general, endothelial cells change their migratory behavior in response to shear stress patterns, according to flow directionality. Here, we assessed the impact of shear stress patterns and flow directionality on the behavior of endocardial cells, the specialized endothelial cells of the heart. At the early stages of zebrafish heart valve formation, we show that endocardial cells are converging to the valve-forming area and that this behavior depends upon mechanical forces. Quantitative live imaging and mathematical modeling allow us to correlate this tissue convergence with the underlying flow forces. We predict that tissue convergence is associated with the direction of the mean wall shear stress and of the gradient of harmonic phase-averaged shear stresses, which surprisingly do not match the overall direction of the flow. This contrasts with the usual role of flow directionality in vascular development and suggests that the full spatial and temporal complexity of the wall shear stress should be taken into account when studying endothelial cell responses to flow in vivo., Summary: Blood flow modeling shows that dynamic shear stress patterns, rather than mean flow direction, predict the stereotypical behavior of endocardial cells during the early steps of heart valve formation.

Mechanical forces are instrumental to cardiovascular development and physiology. The heart beats approximately 2.6 billion times in a human lifetime and heart valves ensure that these contractions result in an efficient, unidirectional flow of the blood. Composed of endocardial cells (EdCs) and extracellular matrix (ECM), cardiac valves are among the most mechanically challenged structures of the body both during and after their development. Understanding how hemodynamic forces modulate cardiovascular function and morphogenesis is key to unraveling the relationship between normal and pathological cardiovascular development and physiology. Most valve diseases have their origins in embryogenesis, either as signs of abnormal developmental processes or the aberrant re-expression of fetal gene programs normally quiescent in adulthood. Here we review recent discoveries in the mechanobiology of cardiac valve development and introduce the latest technologies being developed in the zebrafish, including live cell imaging and optical technologies, as well as modeling approaches that are currently transforming this field. This article is part of a Special Issue entitled: Cardiomyocyte Biology: Integration of Developmental and Environmental Cues in the Heart edited by Marcus Schaub and Hughes Abriel.

Biomechanics and Modeling in Mechanobiology, 12 (2), ISSN:1617-7959, ISSN:1617-7940

During embryogenesis, cells undergo dynamic changes in cell behavior, and deciphering the cellular logic behind these changes is a fundamental goal in the field of developmental biology. The discovery and development of photoconvertible proteins have greatly aided our understanding of these dynamic changes by providing a method to optically highlight cells and tissues. However, while photoconversion, time-lapse microscopy, and subsequent image analysis have proven to be very successful in uncovering cellular dynamics in organs such as the brain or the eye, this approach is generally not used in the developing heart due to challenges posed by the rapid movement of the heart during the cardiac cycle. This protocol consists of two parts. The first part describes a method for photoconverting and subsequently tracking endocardial cells (EdCs) during zebrafish atrioventricular canal (AVC) and atrioventricular heart valve development. The method involves temporally stopping the heart with a drug in order for accurate photoconversion to take place. Hearts are allowed to resume beating upon removal of the drug and embryonic development continues normally until the heart is stopped again for high-resolution imaging of photoconverted EdCs at a later developmental time point. The second part of the protocol describes an image analysis method to quantify the length of a photoconverted or non-photoconverted region in the AVC in young embryos by mapping the fluorescent signal from the three-dimensional structure onto a two-dimensional map. Together, the two parts of the protocol allows one to examine the origin and behavior of cells that make up the zebrafish AVC and atrioventricular heart valve, and can potentially be applied for studying mutants, morphants, or embryos that have been treated with reagents that disrupt AVC and/or valve development.

SummaryIn vertebrates, heart pumping is required for cardiac morphogenesis and altering myocardial contractility leads to abnormal intracardiac flow forces and valve defects [1–3]. Among the different mechanical cues generated in the developing heart, oscillatory flow has been proposed to be an essential factor in instructing endocardial cell fate toward valvulogenesis and leads to the expression of klf2a [4], a known atheroprotective transcription factor [5]. To date, the mechanism by which flow forces are sensed by endocardial cells is not well understood. At the onset of valve formation, oscillatory flows alter the spectrum of the generated wall shear stress (WSS), a key mechanical input sensed by endothelial cells. Here, we establish that mechanosensitive channels are activated in response to oscillatory flow and directly affect valvulogenesis by modulating the endocardial cell response. By combining live imaging and mathematical modeling, we quantify the oscillatory content of the WSS during valve development and demonstrate it sets the endocardial cell response to flow. Furthermore, we show that an endocardial calcium response and the flow-responsive klf2a promoter are modulated by the oscillatory flow through Trpv4, a mechanosensitive ion channel specifically expressed in the endocardium during heart valve development. We made similar observations for Trpp2, a known Trpv4 partner, and show that both the absence of Trpv4 or Trpp2 leads to valve defects. This work identifies a major mechanotransduction pathway involved during valve formation in vertebrates.

Hemodynamic forces are fundamental to development. Indeed, much of cardiovascular morphogenesis reflects a two-way interaction between mechanical forces and the gene network activated in endothelial cells via mechanotransduction feedback loops. As these interactions are becoming better understood in different model organisms, it is possible to identify common mechanogenetic rules, which are strikingly conserved and shared in many tissues and species. Here, we discuss recent findings showing how hemodynamic forces potentially modulate cardiovascular development as well as the underlying fluid and tissue mechanics, with special attention given to the flow characteristics that are unique to the small scales of embryos.

SUMMARY We propose to couple the method of fundamental solutions (MFS) to the force coupling method (FCM). The resulting method is an efficient, easy to program, meshless method for flows at low Reynolds numbers with finite-size particles. In such an approach, the flow domain is extended across the solid particle phase, and the flow is approximated by a superposition of singular Stokeslets positioned outside the flow domain and finite-size multipoles collocated with the particle. To improve the efficiency of the coupling, we propose new MFS quadratures for the computation of the volume integrals required for the FCM. These are exact and do not require the expensive evaluation of Stokeslets. The proposed method has been developed in the context of investigations of the fluid dynamics of canalithiasis, that is, a pathological condition of the semicircular canals of the inner ear. Numerical examples are presented to illustrate the applicability of the method. Copyright © 2013 John Wiley & Sons, Ltd.

The method of fundamental solutions (MFS) is a meshless method for the solution of boundary value problems and has recently been proposed as a simple and efficient method for the solution of Stokes flow problems. The MFS approximates the solution by an expansion of fundamental solutions whose singularities are located outside the flow domain. Typically, the source points (i.e. the singularities of the fundamental solutions) are confined to a smooth source layer embracing the flow domain. This monolayer implementation of the MFS (monolayer MFS) depends strongly on the location of the user-defined source points: On the one hand, increasing the distance of the source points from the boundary tends to increase the convergence rate. On the other hand, this may limit the achievable accuracy. This often results in an unfavorable compromise between the convergence rate and the achievable accuracy of the MFS. The idea behind the present work is that a multilayer implementation of the MFS (multilayer MFS) can improve the robustness of the MFS by efficiently resolving different scales of the solution by source layers at different distances from the boundary. We propose a block greedy-QR algorithm (BGQRa) which exploits this property in a multilevel fashion. The proposed multilayer MFS is much more robust than the monolayer MFS and can compute Stokes flows on general two- and three-dimensional domains. It converges rapidly and yields high levels of accuracy by combining the properties of distant and close source points. The block algorithm alleviates the overhead of multiple source layers and allows the multilayer MFS to outperform the monolayer MFS.

Organogenesis involves extensive and dynamic changes of tissue shape during development. It is associated with complex morphogenetic events that require enormous tissue plasticity and generate a large variety of transient three-dimensional geometries that are achieved by global tissue responses. Nevertheless, such global responses are driven by tight spatio-temporal regulation of the behaviours of individual cells composing these tissues. Therefore, the development of image analysis tools that allow for extraction of quantitative data concerning individual cell behaviours is central to study tissue morphogenesis. There are many image analysis tools available that permit extraction of cell parameters. Unfortunately, the majority are developed for tissues with relatively simple geometries such as flat epithelia. Problems arise when the tissue of interest assumes a more complex three-dimensional geometry. Here, we use the endothelium of the developing zebrafish dorsal aorta as an example of a tissue with cylindrical geometry and describe the image analysis routines developed to extract quantitative data on individual cells in such tissues, as well as the image acquisition and sample preparation methodology. This article is part of the Theo Murphy meeting issue ‘Mechanics of development’.

© 2015 The Authors.Desminopathies belong to a family of muscle disorders called myofibrillar myopathies that are caused by Desmin mutations and lead to protein aggregates in muscle fibers. To date, the initial pathological steps of desminopathies and the impact of desmin aggregates in the genesis of the disease are unclear. Using live, high-resolution microscopy, we show that Desmin loss of function and Desmin aggregates promote skeletal muscle defects and alter heart biomechanics. In addition, we show that the calcium dynamics associated with heart contraction are impaired and are associated with sarcoplasmic reticulum dilatation as well as abnormal subcellular distribution of Ryanodine receptors. Our results demonstrate that desminopathies are associated with perturbed excitation-contraction coupling machinery and that aggregates are more detrimental than Desmin loss of function. Additionally, we show that pharmacological inhibition of aggregate formation and Desmin knockdown revert these phenotypes. Our data suggest alternative therapeutic approaches and further our understanding of the molecular determinants modulating Desmin aggregate formation. Desminopathies are myopathies and cardiomyopathies associated with Desmin mutations leading to protein aggregates. Ramspacher et al. demonstrate that altered Desmin function or expression affect the EC coupling machinery and calcium dynamics. They show that aggregates are more toxic than the loss of function and can be rescued by knockdown and pharmacological treatment.

Primary cilia are necessary for shear stress sensing in different developing organs such as the kidneys and blood vessels. In endothelial cells (ECs), primary cilia bend in response to blood flow forces and are necessary for flow sensing as well as for the control of angiogenesis. The different parameters guiding cilia bending reflect the forces generated at the surface of the ECs and the mechanical properties of the endothelial cilia. Here, we present an approach allowing the calculation of the bending rigidity of endothelial cilia based on live imaging. The method relies on segmentation and mathematical modeling to extract the critical parameters needed for the calculation.

Primary cilia are necessary for shear stress sensing in different developing organs such as the kidneys and blood vessels. In endothelial cells (ECs), primary cilia bend in response to blood flow forces and are necessary for flow sensing as well as for the control of angiogenesis. The different parameters guiding cilia bending reflect the forces generated at the surface of the ECs and the mechanical properties of the endothelial cilia. Here, we present an approach allowing the calculation of the bending rigidity of endothelial cilia based on live imaging. The method relies on segmentation and mathematical modeling to extract the critical parameters needed for the calculation.

In our daily life, small flows in the semicircular canals (SCCs) of the inner ear displace a sensory structure called the cupula which mediates the transduction of head angular velocities to afferent signals. We consider a dysfunction of the SCCs known as canalithiasis. Under this condition, small debris particles disturb the flow in the SCCs and can cause benign paroxysmal positional vertigo (BPPV), arguably the most common form of vertigo in humans. The diagnosis of BPPV is mainly based on the analysis of typical eye movements (positional nystagmus) following provocative head maneuvers that are known to lead to vertigo in BPPV patients. These eye movements are triggered by the vestibulo-ocular reflex, and their velocity provides an indirect measurement of the cupula displacement. An attenuation of the vertigo and the nystagmus is often observed when the provocative maneuver is repeated. This attenuation is known as BPPV fatigue. It was not quantitatively described so far, and the mechanisms causing it remain unknown. We quantify fatigue by eye velocity measurements and propose a fluid dynamic interpretation of our results based on a computational model for the fluid-particle dynamics of a SCC with canalithiasis. Our model suggests that the particles may not go back to their initial position after a first head maneuver such that a second head maneuver leads to different particle trajectories causing smaller cupula displacements.

International audience; The pattern of blood flow has long been thought to play a significant role in vascular morphogenesis, yet the flow-sensing mechanism that is involved at early embryonic stages, when flow forces are low, remains unclear. It has been proposed that endothe-lial cells use primary cilia to sense flow, but this has never been tested in vivo. Here we show, by non-invasive, high-resolution imaging of live zebrafish embryos, that endothelial cilia progressively deflect at the onset of blood flow and that the deflection angle correlates with calcium levels in endothelial cells. We demonstrate that alterations in shear stress, ciliogenesis, or expression of the calcium channel PKD2 impair the endothelial calcium level and both increase and perturb vascular morpho-genesis. Altogether, these results demonstrate that endothelial cilia constitute a highly sensitive structure that permits the detection of low shear forces during vascular morphogenesis.

Benign paroxismal positional vertigo (BPPV) is modeled by introducing free-floating particles (canaliths) which settle inside the semicircular canals (SCC). The Stokes flow induced by a canalith is evaluated by coupling the force coupling method (FCM) to the method of fundamental solutions (MFS). The proposed methodology results in a straightforward meshless boundary method for the simulation of bounded Stokes flow with finite-size particles. (© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim)

We present a numerical model for the simulation of the flow in semicircular canals (SCCs). The governing equations for the flow are solved with the method of fundamental solutions (MFS), a mesh free method for boundary value problems. We describe the flow field in a SCC with utricle, and we find a vortex that had not yet been reported in literature. (© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim)