Smart soft contact lenses for continuous 24-hour monitoring of intraocular pressure in glaucoma care.

Continuous monitoring of intraocular pressure, particularly during sleep, remains a grand challenge in glaucoma care. Here we introduce a class of smart soft contact lenses, enabling the continuous 24-hour monitoring of intraocular pressure, even during sleep. Uniquely, the smart soft contact lenses are built upon various commercial brands of soft contact lenses without altering their intrinsic properties such as lens power, biocompatibility, softness, transparency, wettability, oxygen transmissibility, and overnight wearability. We show that the smart soft contact lenses can seamlessly fit across different corneal curvatures and thicknesses in human eyes and therefore accurately measure absolute intraocular pressure under ambulatory conditions. We perform a comprehensive set of in vivo evaluations in rabbit, dog, and human eyes from normal to hypertension to confirm the superior measurement accuracy, within-subject repeatability, and user comfort of the smart soft contact lenses beyond current wearable ocular tonometers. We envision that the smart soft contact lenses will be effective in glaucoma care.

An ASIC System for Closed-Loop Blood Pressure Modulation Through Right Cervical Vagus Nerve Stimulation.

OBJECTIVE: Heart disease is the leading cause of death worldwide. Hypertension is an important precursor and the most common risk factor to heart failure. While some patients can control their high blood pressure with pharmaceuticals, many suffer from resistant hypertension, where antihypertensive medications do not achieve the desired outcome. Electrical stimulation is an emerging therapy to modulate blood pressure and integrating it with closed-loop feedback can improve blood pressure control. METHODS: We design and fabricate two application-specific integrated circuits (ASICs) for stimulation and pressure sensing using TSMC's 180 nm MS RF G process. We create a closed-loop system by integrating the ASICs with a microscale pressure sensor and a custom-built Python script and test the full system in six Long Evans rats using vagus nerve stimulation. RESULTS: After calibration and benchtop verification, we prove the functionality of the system in lowering, and maintaining a desired blood pressure in vivo. The system effectively monitors pressure and stimulates when that pressure exceeds the user-determined threshold. CONCLUSION: By combining this stimulation therapy with a pressure sensor, we present a novel closed-loop, electroceutical system that has the potential to monitor and modulate blood pressure. SIGNIFICANCE: We present a drug-free, potentially side-effect-free electroceutical therapeutic for managing resistant hypertension.

A Highly Miniaturized, Chronically Implanted ASIC for Electrical Nerve Stimulation.

We present a wireless, fully implantable device for electrical stimulation of peripheral nerves consisting of a powering coil, a tuning network, a Zener diode, selectable stimulation parameters, and a stimulator IC, all encapsulated in biocompatible silicone. A wireless RF signal at 13.56 MHz powers the implant through the on-chip rectifier. The ASIC, designed in TSMC's 180 nm MS RF G process, occupies an area of less than 1.2 mm2. The IC enables externally selectable current-controlled stimulation through an on-chip read-only memory with a wide range of 32 stimulation parameters (90-750 µA amplitude, 100 µs or 1 ms pulse width, 15 or 50 Hz frequency). The IC generates the constant current waveform using an 8-bit binary weighted DAC and an H-Bridge. At the most power-hungry stimulation parameter, the average power consumption during a stimulus pulse is 2.6 mW with a power transfer efficiency of ∼5.2%. In addition to benchtop and acute testing, we chronically implanted two versions of the device (a design with leads and a leadless design) on two rats' sciatic nerves to verify the long-term efficacy of the IC and the full system. The leadless device had the following dimensions: height of 0.45 cm, major axis of 1.85 cm, and minor axis of 1.34 cm, with similar dimensions for the device with leads. Both devices were implanted and worked for experiments lasting from 21-90 days. To the best of our knowledge, the fabricated IC is the smallest constant-current stimulator that has been tested chronically.

Parylene-C Microbore Tubing: A Simpler Shunt for Reducing Intraocular Pressure.

OBJECTIVE: Current minimally-invasive glaucoma surgery (MIGS) devices promise to control elevated levels of intraocular pressure (IOP) while avoiding many of the downsides of traditional glaucoma surgery. However, there remains room for improvement in performance metrics, including drainage efficacy, device longevity, and time to implant, as outlined by benchmarks set forth by the Audacious Goals Initiative. We introduce a better shunt, which achieves similar or improved pre-clinical safety and efficacy outcomes to commercial MIGS devices, while reducing surgical profile and implantation time. METHODS: We developed a parylene-based microbore glaucoma drainage device capable of modulating IOP via a minimally-invasive implantation procedure. We surgically implanted microbore tubing in five healthy New Zealand White rabbits and measured IOP levels biweekly using handheld applanation tonometry to assess device efficacy in lowering and maintaining IOP. After 6 weeks, the rabbits were euthanized and eyes were enucleated to evaluate inflammatory and histologic response to a foreign-body implant. RESULTS: This device is the only one that fulfills the 10-minute benchmark for implantation time compared to other commercial MIGS devices. In 4 of 5 animals implanted, post-op IOP in the experimental eye dropped by an average of 16.17%. Histopathologic evaluation revealed localized evidence of minor inflammatory reaction and tissue irritation, as well as minimal fibrosis along the tube-tissue interface. CONCLUSION AND SIGNIFICANCE: Based on these findings, this device stands as a promising platform to lowering IOP, particularly in patients with mild to moderate glaucoma requiring no need for cataract intervention, withouteliciting a severe biological response.

Semi-permanent transcorneal filter support and in vivo surgical implantation technique for open-angle glaucoma treatment.

Primary open-angle glaucoma is a progressive disease affecting nearly 60 million people worldwide which, if left untreated, can lead to optic nerve head damage and complete loss of sight. Current interventions include: pharmaceutical drops, laser surgery, shunts, and bleb; however, these methods provide insufficient long-term efficacy in intraocular pressure management. We developed a semi-permanent, implantable transcorneal duct as a new aid in the treatment of this disease. The duct, composed of an intracorneal stabilizing washer and hollow screw, creates an interface between the anterior chamber and the external environment, allowing for the outflow of excess aqueous humor. We discuss the fluid mechanics behind designing and implementing a filter material capable of preventing the ingress of bacteria and viruses while modifying aqueous humor outflow resistances to pre-glaucomatous levels, finding the effective radius of such a material to be 10.44 µm. After performing surgical implantation in four rabbit eyes, subsequent testing showed successful integration between the screw and washer. Colored saline injections highlighted fluid flow progression out of the eye through the duct, suggesting that the device may be a viable approach to treating high intraocular pressure created by open-angle glaucoma.