Microfluidics in the eye: a review of glaucoma implants from an engineering perspective.

Glaucoma is a progressive optic neuropathy in the eye, which is a leading cause of irreversible blindness worldwide and currently affects over 70 million individuals. Clinically, intraocular pressure (IOP) reduction is the only proven treatment to halt the progression of glaucoma. Microfluidic devices such as glaucoma drainage devices (GDDs) and minimally invasive glaucoma surgery (MIGS) devices are routinely used by ophthalmologists to manage elevated IOP, by creating an artificial pathway for the over-accumulated aqueous humor (AH) in a glaucomatous eye, when the natural pathways are severely blocked. Herein, a detailed modelling and analysis of both the natural microfluidic pathways of the AH in the eye and artificial microfluidic pathways formed additionally by the various glaucoma implants are conducted to provide an insight into the causes of the IOP abnormality and the improvement schemes of current implant designs. The mechanisms of representative glaucoma implants have been critically reviewed from the perspective of microfluidics, and we have categorized the current implants into four groups according to the targeted drainage sites of the AH, namely Schlemm's canal, suprachoroidal space, subconjunctival space, and ocular surface. In addition, we propose to divide the development and evolution of glaucoma implant designs into three technological waves, which include microtube (1st), microvalve (2nd) and microsystem (3rd). With the emerging trends of minimal invasiveness and artificial intelligence in the development of medical implants, we envision that a comprehensive glaucoma treatment microsystem is on the horizon, which is featured with active and wireless control of IOP, real-time continuous monitoring of IOP and aqueous rate, etc. The current review could potentially cast light on the unmatched needs, challenges, and future directions of the microfluidic structural and functional designs of glaucoma implants, which would enable an enhanced safety profile, reduced complications, increased efficacy of lowering IOP and reduced IOP fluctuations, closed-loop and on-demand control of IOP, etc.

Predicting the Effect of Adding a Citizenship Question to the 2020 Census.

The addition of a citizenship question to the 2020 census could affect the self-response rate, a key driver of the cost and quality of a census. We find that citizenship question response patterns in the American Community Survey (ACS) suggest that it is a sensitive question when asked about administrative record noncitizens but not when asked about administrative record citizens. ACS respondents who were administrative record noncitizens in 2017 frequently choose to skip the question or answer that the person is a citizen. We predict the effect on self-response to the entire survey by comparing mail response rates in the 2010 ACS, which included a citizenship question, with those of the 2010 census, which did not have a citizenship question, among households in both surveys. We compare the actual ACS-census difference in response rates for households that may contain noncitizens (more sensitive to the question) with the difference for households containing only U.S. citizens. We estimate that the addition of a citizenship question will have an 8.0 percentage point larger effect on self-response rates in households that may have noncitizens relative to those with only U.S. citizens. Assuming that the citizenship question does not affect unit self-response in all-citizen households and applying the 8.0 percentage point drop to the 28.1 % of housing units potentially having at least one noncitizen would predict an overall 2.2 percentage point drop in self-response in the 2020 census, increasing costs and reducing the quality of the population count.

Design, Fabrication, and In Vitro Testing of an Anti-biofouling Glaucoma Micro-shunt.

Glaucoma, one of the leading causes of irreversible blindness, is a progressive neurodegenerative disease. Chronic elevated intraocular pressure (IOP), a prime risk factor for glaucoma, can be treated by aqueous shunts, implantable devices, which reduce IOP in glaucoma patients by providing alternative aqueous outflow pathways. Although initially effective at delaying glaucoma progression, contemporary aqueous shunts often lead to numerous complications and only 50% of implanted devices remain functional after 5 years. In this work, we introduce a novel micro-device which provides an innovative platform for IOP reduction in glaucoma patients. The device design features an array of parallel micro-channels to provide precision aqueous outflow resistance control. Additionally, the device's microfluidic channels are composed of a unique combination of polyethylene glycol materials in order to provide enhanced biocompatibility and resistance to problematic channel clogging from biofouling of aqueous proteins. The microfabrication process employed to produce the devices results in additional advantages such as enhanced device uniformity and increased manufacturing throughput. Surface characterization experimental results show the device's surfaces exhibit significantly less non-specific protein adsorption compared to traditional implant materials. Results of in vitro flow experiments verify the device's ability to provide aqueous resistance control, continuous long-term stability through 10-day protein flow testing, and safety from risk of infection due to bacterial ingression.

Energy efficiency and reliability in wireless biomedical implant systems.

The use of wireless implant technology requires correct delivery of the vital physiological signs of the patient along with the energy management in power-constrained devices. Toward these goals, we present an augmentation protocol for the physical layer of the medical implant communications service (MICS) with focus on the energy efficiency of deployed devices over the MICS frequency band. The present protocol uses the rateless code with the frequency-shift keying (FSK) modulation scheme to overcome the reliability and power cost concerns in tiny implantable sensors due to the considerable attenuation of propagated signals across the human body. In addition, the protocol allows a fast start-up time for the transceiver circuitry. The main advantage of using rateless codes is to provide an inherent adaptive duty cycling for power management, due to the flexibility of the rateless code rate. Analytical results demonstrate that an 80% energy saving is achievable with the proposed protocol when compared to the IEEE 802.15.4 physical layer standard with the same structure used for wireless sensor networks. Numerical results show that the optimized rateless coded FSK is more energy efficient than that of the uncoded FSK scheme for deep tissue (e.g., digestive endoscopy) applications, where the optimization is performed over modulation and coding parameters.

An artificial nano-drainage implant (ANDI) for glaucoma treatment.

Glaucoma is the leading cause of irreversible blindness. The loss of sight in glaucoma is due to the permanent optic nerve damage which is the result of a chronic elevated intraocular pressure. In this paper, we report a completely new concept to treat glaucoma using a nano-drainage device fabricated through MEMS and nanofabrication technologies. This involves replacing the functionality of diseased drainage pathway for aqueous humor outflow (i.e., trabecular meshwork). By enhancing aqueous humor outflow, the artificial drainage implant will lead to a decrease in the intraocular pressure and a halt in the progression of glaucoma.

Thin-film coupled fluid-solid analysis of flow through the Ahmed glaucoma drainage device.

The Ahmed glaucoma valve (AGV) is a popular glaucoma drainage device, allowing maintenance of normal intraocular pressure in patients with reduced trabecular outflow facility. The uniquely attractive feature of the AGV, in contrast to other available drainage devices, is its variable resistance in response to changes in flow rate. As a result of this variable resistance, the AGV maintains a pressure drop between 7 and 12 mm Hg for a wide range of aqueous humor flow rates. In this paper, we demonstrate that the nonlinear behavior of the AGV is a direct result of the flexibility of the valve material. Due to the thin geometry of the system, the leaflets of the AGV were modeled using the von Kármán plate theory coupled to a Reynolds lubrication theory model of the aqueous humor flow through the valve. The resulting two-dimensional coupled steady-state partial differential equation system was solved by the finite element method. The Poisson's ratio of the valve was set to 0.45, and the modulus was regressed to experimental data, giving a best-fit value 4.2 MPa. Simulation results compared favorably with previous experimental studies and our own pressure-drop/flow-rate data. For an in vitro flow of 1.6 microL/min, we calculated a pressure drop of 5.8 mm Hg and measured a pressure drop of 5.2 +/- 0.4 mm Hg. As flow rate was increased, pressure drop rose in a strongly sublinear fashion, with a flow rate of 20 microL/min giving a predicted pressure drop of only 10.9 mm Hg and a measured pressure drop of 10.5 +/- 1.1 mm Hg. The AGV model was then applied to simulate in vivo conditions. For an aqueous humor flow rate of 1.5-3.0 microL/min, the calculated pressure drops were 5.3 and 6.3 mm Hg.

Modeling and characterization of a valved glaucoma drainage device with implications for enhanced therapeutic efficacy.

We report on modeling and bench test results targeted at better understanding of valved glaucoma drainage devices (GDDs), a common current surgical treatment for glaucoma. A simple equivalent circuit is described to model fluid mechanical behavior of the aqueous humor in an eye with glaucoma, both before and after implantation of a valved GDD. Finite element method simulations (FEM), based on the lubrication-von Kármán model, are then performed to analyze the valve's mechanical and fluidic performance. Using nanoporous membranes to mimic the in vivo fibrous capsule, we have developed a microfluidic bench test to simulate the aqueous humor flow and the post-implantation fibrous tissue encapsulation around the GDD back plate. Our numerical and bench test results show that, contrary to the prevailing belief, the valve significantly contributes to the total pressure drop even after fibrous capsule formation. Furthermore, we show that bypassing the valve through a simple polyimide tube insertion will dramatically lower the intraocular pressure (IOP) after fibrous capsule formation. This may offer a new treatment option in some patients with advanced glaucoma.