The vascular geometry of the choriocapillaris is associated with spatially heterogeneous molecular exchange with the outer retina.

Vision relies on the continuous exchange of material between the photoreceptors, retinal pigment epithelium and choriocapillaris, a dense microvascular bed located underneath the outer retina. The anatomy and physiology of the choriocapillaris and their association with retinal homeostasis have proven difficult to characterize, mainly because of the unusual geometry of this vascular bed. By analysing tissue dissected from 81 human eyes, we show that the thickness of the choriocapillaris does not vary significantly over large portions of the macula or with age. Assessments of spatial variations in the anatomy of the choriocapillaris in three additional human eyes indicate that the location of arteriolar and venular vessels connected to the plane of the choriocapillaris is non-random, and that venular insertions cluster around arteriolar ones. Mathematical models built upon these anatomical analyses reveal that the choriocapillaris contains regions where the transport of passive elements is dominated by diffusion, and that these diffusion-limited regions represent areas of reduced exchange with the outer retina. The width of diffusion-limited regions is determined by arterial flow rate and the relative arrangement of arteriolar and venular insertions. These analyses demonstrate that the apparent complexity of the choriocapillaris conceals a fine balance between several anatomical and functional parameters to effectively support homeostasis of the outer retina. KEY POINTS: The choriocapillaris is the capillary bed supporting the metabolism of photoreceptors and retinal pigment epithelium, two critical components of the visual system located in the outer part of the retina. The choriocapillaris has evolved a planar multipolar vascular geometry that differs markedly from the branched topology of most vasculatures in the human body. Here, we report that this planar multipolar vascular geometry is associated with spatially heterogenous molecular exchange between choriocapillaris and outer retina. Our data and analyses highlight a necessary balance between choriocapillaris anatomical and functional parameters to effectively support homeostasis of the outer retina.

Modelling the compression of a soft ellipsoid fingertip.

A purely mechanical-driven haptic feedback system was developed for amputees by [G. Shi et al., IEEE Trans. Haptics, 2020, 13, 204-210]. The fingertip ellipsoid modulates the compression force and transmits it to the feedback actuator when the finger interacts with an object. In this paper, the haptic feedback system has been modelled using finite deformation theory. For the ellipsoid fingertip, the compression behaviour between two rigid, flat surfaces has been studied and can predict the force-indentation trend and deformed shape of the membrane with the contact area. For the feedback actuator, the model for the flat membrane is developed with elastic theory, in which the deformation resulting in contact area increase has been studied. The model has been validated with experimental results, which consists of the fingertip ellipsoid membrane being compressed by a rigid surface and the feedback actuator being pressurised. The results of force-indentation, pressure-indentation and the deformation of the membrane from ellipsoid modelling lay within the experimental data and fit the non-linear trend well. The results from modelling the feedback actuator have the same trend as the experimental data in the force-pressure relationship. The haptic feedback system is consistent as a functional tactile sensor after validation. We present the modelling and validation of the proposed model for the mechanical driven haptic feedback system.

Spread of infectious agents through the air in complex spaces.

The fluid mechanical processes that govern the spread of infectious agents through the air in complex spaces are reviewed and the scientific gaps and challenges identified and discussed. Air, expelled from the nose and mouth, creates turbulent jets that form loosely coherent structures which quickly slow. For the transport and dispersion of aerosols, the suitability of the Eulerian as well as the Lagrangian approaches are brought into context. The effects of buoyancy and external turbulence are explored and shown to influence the horizontal extent of expulsion through distinct mechanisms which both inhibit penetration and enhance mixing. The general influence of inhomogeneous turbulence and stratification on the spread of infectious agents in enclosed complex spaces is discussed.

Removal and dispersal of biofluid films by powered medical devices: Modeling infectious agent spreading in dentistry.

Medical procedures can disperse infectious agents and spread disease. Particularly, dental procedures may pose a high risk of disease transmission as they use high-powered instruments operating within the oral cavity that may contain infectious microbiota or viruses. Here we assess the ability of powered dental devices in removing the biofluid films and identified mechanical, hydrodynamic, and aerodynamic forces as the main underlying mechanisms of removal and dispersal processes. Our results indicate that potentially infectious agents can be removed and dispersed immediately after dental instrument engagement with the adherent biofluid film, while the degree of their dispersal is rapidly depleted owing to the removal of the source and dilution by the coolant water. We found that droplets created by high-speed drill interactions typically travel ballistically, while aerosol-laden air tends to flow as a current over surfaces. Our mechanistic investigation offers plausible routes for reducing the spread of infection during invasive medical procedures.

Translating Minimally Invasive Glaucoma Surgery Devices.

Glaucoma is the leading cause of irreversible blindness with over 70 million people affected worldwide. The surgical management of glaucoma aims to lower intraocular pressure by increasing aqueous outflow facility. The latest manufacturing techniques have allowed for the development of a number of novel implantable devices to improve safety and outcomes of glaucoma surgery. These are collectively referred to as minimally invasive glaucoma surgery (MIGS) devices and are among the smallest devices implanted in the human body. This review discusses the design criterion and constraints as well as the user requirements for MIGS devices. We review how recent devices have attempted to meet these challenges and give our opinion as to the necessary characteristics for the development of future devices.

Novel approaches to model effects of subconjunctival blebs on flow pressure to improve clinical grading systems after glaucoma drainage surgery.

Clinical grading systems following glaucoma filtration surgery do not include any effects of the bleb on the intra-ocular pressure and are relatively subjective, therefore carrying the risk of inter and/or intra-observer variability. The main objective of the study is to quantify and model the effect of subconjunctival bleb on flow pressure for assessment of clinical grading following glaucoma surgery. Subconjunctival bleb was created by inserting a tube into ex vivo rabbit eyes via an ab externo approach through the anterior chamber and exiting into the subconjunctival space. Sterile dyed water was injected through the tube into the developing bleb. For the in vitro approach a silicone bleb was created by clamping a circular silicone sheet, injecting dyed water through a fixed resistance outlet tube. Photographic measurements of the bleb height, planform area and pressure were taken as a function of time. Clinical blebs were also collected over a few months. Mathematical algorithm software was used to build the bleb model. Bleb height and volume increase as pressure in the bleb increases. The bleb planform area tended to a constant determined by the section of conjunctiva prior to shunt insertion. These increases were in accordance with the bleb model developed in the Appendix. They show that the pressure in the bleb is related to the resistance of the outflow. The linearity of clinical grading systems is reviewed and a new grading approach is proposed. The pressure in the bleb has a strong dependence on bleb extent, height and a weak dependence on conjunctival thickness. The pressure in a bleb can be estimated from bleb height, radius, and flow rate inlet in agreement with the bleb flow model. These results provide support for an improved bleb categorization system.

The Implications of an Ab Interno Versus Ab Externo Surgical Approach on Outflow Resistance of a Subconjunctival Drainage Device for Intraocular Pressure Control.

PURPOSE: Minimally invasive glaucoma surgery (MIGS) devices that drain into the subconjunctival space can be inserted via an ab externo or ab interno approach. Limited experimental data exists as to the impact of either technique on intraocular pressure (IOP) control. We performed microfluidic studies by using ex vivo rabbit eyes to assess the effect of each approach on outflow resistance of a subconjunctival drainage device for IOP control. METHODS: A microfluidic experiment system was designed, consisting of a controlled reservoir of water connected to a pressure pump/flow sensor. The flow rate of water was fixed at 2 µl/min to simulate aqueous humor production. The pressure readings for each approach were recorded at a frequency of 1 Hz. A baseline reading was made before tube insertion into the eye (PEEK tube length set to aim for an initial outflow resistance of 5 to 10 mm Hg/µL/min) followed by measurements for a cumulative 2-ml volume entering the subconjunctival space. Results were adjusted for water viscosity at 37°C and reported as outflow resistance (mm Hg/µL/min ± standard error of mean). RESULTS: Outflow resistance via the ab interno approach was 90.4% higher than with the ab externo approach being measured at 0.80 ± 0.11 mm Hg/µL/min and 0.42 ± 0.05 mm Hg/µL/min, respectively. Bleb formation was observed to be less predictable with the ab interno approach. CONCLUSIONS: The ab interno approach demonstrated greater outflow resistance and less predictable bleb formation than the ab externo approach. These results have implications for long-term IOP control and success depending on the approach to device insertion and could be an important consideration for future MIGS devices. TRANSLATIONAL RELEVANCE: The effect of the ab interno versus ab externo approach of a MIGS device inserted into the subconjunctival space was assessed. The ab interno approach demonstrated greater outflow resistance and less predictable bleb formation that may have implications for the development of future MIGS devices.

A Case Report of Complete Blockage of a Baerveldt Glaucoma Implant Following Insertion of a 3-0 Supramid Suture.

PURPOSE: The aim of this study was to present a case of a Baerveldt glaucoma implant lumen being completely occluded with a 3-0 Supramid stent suture. PATIENT AND METHODS: The patient underwent Baerveldt glaucoma implant surgery with placement of an intraluminal 3-0 Supramid stent suture that acts to restrict flow across the device and reduce the risk of postoperative hypotony. Following suturing of the implant to the sclera, the device was flow tested. No flow was observed through the device tube and a significant ballooning of the tube diameter occurred with increased pressure on the device. The device was explanted from the eye and replaced with a different implant without further postoperative complication. The explanted device was assessed using custom microfluidic equipment in an in vitro environment. RESULTS: This phenomenon occurred despite using several different batches of the 3-0 Supramid stent suture and the device had to be removed and replaced with another device without complication. In vitro microfluidic assessment of the device demonstrated no flow across the device tube despite over 150 mm Hg of pressure being exerted on the device. CONCLUSIONS: We hypothesize that the blockage occurred at the junction between the device tube and plate and that the ballooning phenomenon observed was due to a defect in the tube wall. This case highlights the importance of flow testing all glaucoma drainage devices before insertion given the variation in manufacturing conditions to avoid the risk of intraoperative complications.

Allometry and Scaling of the Intraocular Pressure and Aqueous Humour Flow Rate in Vertebrate Eyes.

In vertebrates, intraocular pressure (IOP) is required to maintain the eye into a shape allowing it to function as an optical instrument. It is sustained by the balance between the production of aqueous humour by the ciliary body and the resistance to its outflow from the eye. Dysregulation of the IOP is often pathological to vision. High IOP may lead to glaucoma, which is in man the second most prevalent cause of blindness. Here, we examine the importance of the IOP and rate of formation of aqueous humour in the development of vertebrate eyes by performing allometric and scaling analyses of the forces acting on the eye during head movement and the energy demands of the cornea, and testing the predictions of the models against a list of measurements in vertebrates collated through a systematic review. We show that the IOP has a weak dependence on body mass, and that in order to maintain the focal length of the eye, it needs to be an order of magnitude greater than the pressure drop across the eye resulting from gravity or head movement. This constitutes an evolutionary constraint that is common to all vertebrates. In animals with cornea-based optics, this constraint also represents a condition to maintain visual acuity. Estimated IOPs were found to increase with the evolution of terrestrial animals. The rate of formation of aqueous humour was found to be adjusted to the metabolic requirements of the cornea, scaling as Vac(0.67), where Vac is the volume of the anterior chamber. The present work highlights an interdependence between IOP and aqueous flow rate crucial to ocular function that must be considered to understand the evolution of the dioptric apparatus. It should also be taken into consideration in the prevention and treatment of glaucoma.

The Influence of Scleral Flap Thickness, Shape, and Sutures on Intraocular Pressure (IOP) and Aqueous Humor Flow Direction in a Trabeculectomy Model.

PURPOSE: Intraocular pressure and aqueous humor flow direction determined by the scleral flap immediately after trabeculectomy are critical determinants of the surgical outcome. We used a large-scale model to objectively measure the influence of flap thickness and shape, and suture number and position on pressure difference across the flap and flow of fluid underneath it. METHODS: The model exploits the principle of dynamic and geometric similarity, so while dimensions were up to 30× greater than actual, the flow had similar properties. Scleral flaps were represented by transparent 0.8- and 1.6-mm-thick silicone sheets on an acrylic plate. Dyed 98% glycerin, representing the aqueous humor was pumped between the sheet and plate, and the equilibrium pressure measured with a pressure transducer. Image analysis based on the principle of dye dilution was performed using MATLAB software. RESULTS: The pressure drop across the flap was larger with thinner flaps, due to reduced rigidity and resistance. Doubling the surface area of flaps and reducing the number of sutures from 5 to 3 or 2 also resulted in larger pressure drops. Flow direction was affected mainly by suture number and position, it was less toward the sutures and more toward the nearest free edge of the flap. Posterior flow of aqueous humor was promoted by placing sutures along the sides while leaving the posterior edge free. CONCLUSION: We demonstrate a new physical model which shows how changes in scleral flap thickness and shape, and suture number and position affect pressure and flow in a trabeculectomy.

Evaluation of Dimensional and Flow Properties of ExPress Glaucoma Drainage Devices.

PURPOSE: ExPress devices are available as P50 and P200 models, the numbers related to their luminal diameters in µm. We compared their Poiseuille's Law-based theoretical resistance values with experimental values and correlated these with their luminal dimensions derived from electron microscopy. METHODS: Scanning electron microscopy was performed on P50 and P200 devices. Bench-top flow studies were performed to find the resistances of the devices. Devices were also incorporated into a perfused, ex vivo porcine sclera model to test and compare their control of pressure, with and without overlying scleral flaps, and with trabeculectomies. RESULTS: The luminal dimensions of the P200 device were 206.4±3.3 and 204.5±0.9 µm at the subconjunctival space and anterior chamber ends, respectively. Those of the P50 device were 205.0±5.8 and 206.9±3.7 µm, respectively. There were no significant differences between the P200 and P50 devices (all P>0.05). The resistances of the P200 and P50 devices were 0.010±0.001 and 0.054±0.002 mm Hg/µL/min, respectively (P<0.05). Equilibrium pressures with overlying scleral flaps were 17.81±3.30 mm Hg for the P50, 17.31±4.24 mm Hg for the P200, and 16.28±6.67 mm Hg for trabeculectomies (P=0.850). CONCLUSIONS: The luminal diameters of both devices are externally similar. The effective luminal diameter of the P50 is much larger than 50 µm. Both devices have low resistance values, making them unlikely to prevent hypotony on their own. They lead to similar equilibrium pressures as the trabeculectomy procedure when inserted under the scleral flap.

Theoretical, experimental, and optical coherence tomography (OCT) studies of graft apposition and adhesion in Descemets stripping automated endothelial keratoplasty (DSAEK).

PURPOSE: To investigate the effects of adhesion promoting surgical adjuncts in Descemets stripping automated endothelial keratoplasty (DSAEK). The effects of air-fill pressure, duration, use of venting incisions and stromal roughening on fluid dispersion, and donor adhesion strength were examined in theoretical, optical coherence tomography (OCT), and strain gauge models of DSAEK. METHODS: OCT analysis: DSAEK modeled using a microkeratome prepared lenticule inserted under a "recipient" corneo-scleral rim mounted on an artificial anterior chamber. Pressure of 18 mm Hg (n = 6) or 60 mm Hg (n = 6) was applied. The area of interface fluid was measured sequentially. The area of interface fluid before and after opening of venting incisions was measured (n = 6). Adhesion experiments: Direct measurement of adhesion force using a universal testing machine was performed. Peak adhesion after compression at 60 mm Hg/8 minutes, 60 mm Hg/1 minutes, 18 mm Hg/8 minutes, and 18 mm Hg/1 minutes (n = 8 each group) was measured. Subsequently, adhesion after complete removal of interface fluid and after stromal roughening was measured in separate samples (n = 12). RESULTS: Interface fluid diminishes with time during tamponade at both low and high pressures (P < 0.0001). Pressure had no effect on amount or rate of fluid dispersion. Venting incisions eliminated interface fluid in all samples when opened sufficiently. Adhesion is independent of anterior chamber air tamponade pressure (P = 0.38). Complete removal of interface fluid increases average adhesion (16.0 mN vs. 7.8 mN, P = 0.0001). Roughening of the host stroma increased adhesion (13.8 mN vs. 9.8 mN, P = 0.0034). CONCLUSIONS: Venting incisions and stromal roughening aid adhesion in DSAEK. Sustained high-pressure anterior chamber air tamponade has no demonstrable effect on measured fluid dispersion or adhesion strength.

Intraocular fluid dynamics and retinal shear stress after vitrectomy and gas tamponade.

PURPOSE: To evaluate fluid dynamics and fluid shear stress on the retinal wall in a model eye after vitrectomy and gas tamponade in relation to saccadic eye movements and sudden head movements and to correlate the results with gas fill fraction (GF). Methods. Analyses was undertaken using high-resolution computational fluid dynamic software. The fluid volume within the eye was discretized using 6 × 10(5) elements and solved with a volume-of-fluid METHOD: The eye was abstracted to a sphere. Vertical and horizontal saccades and sudden rectilinear displacement of the head were examined. GF was varied from 20% to 80% of the eye height filled with gas. RESULTS: Maximum shear stress during horizontal and vertical saccades was 1.0 Pa (Pascal) and 2.5 Pa, respectively, and was dependent on GF. Rapid rectilinear acceleration of the head caused a maximum shear stress of 16 Pa, largely independent of GF. Fluid sloshing within the eye decayed within 0.1 second. Stresses were maximum at the contact line and equator of the eye and were parallel to the direction of motion. CONCLUSIONS: This study predicts that saccadic eye movements and normal head movements after vitrectomy and gas tamponade generate only small fluid shear stresses on the retina that are below published norms for retinal adhesion strength. Sudden, jerking head movements generate fluid shear forces similar to retinal adhesion strength that localize to the area of gas-fluid interface. Fluid sloshing occurs after movement, but rapidly decays on cessation of movement. These results suggest that restrictive posturing after vitrectomy and gas tamponade may be unnecessary. Patients should avoid sudden head movements.

A theoretical model for predicting interfacial relationships of retinal tamponades.

Purpose. To establish a theoretical model to determine the relationship between retinal coverage and tamponade shape in relation to tamponade volume, for a variety of tamponades, and to test these relationships with a physical analogue of the human eye. Methods. The theoretical model was based on a static balance between buoyancy forces and surface tension forces, for an axisymmetrically shaped bubble or droplet. In the laboratory experiments, two hemispheres were cut into an acrylic block. The acrylic was soaked with bovine serum for 10 minutes to ensure that the wetting properties were similar to the human retina. Photographic images of various fractions of lighter-than-water (gas, silicone) and heavier-than-water (Oxane HD) tamponades were analyzed by using algorithms written in commercial image-processing software and compared with the theoretical predictions and published data. Results. The theoretical predictions of tamponade shape and retinal coverage agree closely with the results obtained from the analogue experiments. Conclusions. The theoretical model was validated against measurements in a human eye analogue and published data. The three key parameters that characterize the retinal coverage of any given tamponade are the bond number, the contact angle of the tamponade, and the volume used. The model may be used to predict the static properties of new tamponades without in vivo tests.