Continuous Intraocular Pressure Monitoring Research Articles

LC contact lens sensor for ultrasensitive intraocular pressure monitoring

Twenty-four hours continuous intraocular pressure (IOP) monitoring is beneficial for glaucoma care. Contact lens sensors using LC technology can achieve non-invasive continuous IOP measuring around the clock and are relatively simple in principle and structure, thus dominating the mainstream. Among them, stretchable inductive LC contact lens sensors constructed with liquid metal have advantages in signal quality as well as wearing comfort, but currently its sensitivity is slightly insufficient. Here, we propose an LC sensor that constructed with liquid metal to form the stretchable inductance and capacitance further. The capacitive plate and inductive coil can response to IOP changes simultaneously, thus able to enhance the sensitivity in principle. We modeled the sensing mechanism and conducted design, fabrication, as well as various tests. The device exhibits good characteristics, including reliability, good signal quality, etc. Especially, it has a threefold increase in sensitivity, exceeding the current state-of-the-art contact lens sensors.

Liquid-alloy-based dual sensing elements contact lens sensor for continuous intraocular pressure monitoring

Intraocular pressure (IOP) fluctuation is an independent risk factor for glaucoma and a key to clarify its pathogenesis. We have developed a contact lens integrated with a conformal LC resonance circuit made of liquid alloy (Galinstan) for non-invasive continuous IOP monitoring. The contact lens is fabricated using polydimethylsiloxane (PDMS), in which the LC resonance circuit can sense corneal strain proportionally caused by IOP variation. The Galinstan configuration is formed to the designed pattern by UV-laser treating the carbon-doped Ecoflex (c-Ecoflex) stamps and then selectively transferring the Galinstan onto the stamp to form the LC resonance circuit pattern. The tests conducted on silicone model eyes demonstrate high sensitivity in the frequency responses to variations in IOP, reaching 649 ppm/mmHg. IOP measurement on human eyes during head-down tilt bedrest confirms its applicability. With process optimization, this contact lens sensor has great potential for mass production and wide application in monitoring IOP.

Non-invasive FBG-based contact lens for continuous intraocular pressure monitoring

The intraocular pressure (IOP), or pressure inside the eye, is one of the key indicator for glaucoma diagnosis and treatment. The present work shows the design and fabrication of a non-invasive Fiber Bragg Grating (FBG) based contact lens for continuous IOP monitoring. By employing wet etching to reduce the FBG diameter, FBG based contact lens sensitivity and mechanical flexibility are enhanced. The contact lens is made of an optical fiber with a small core diameter that has an inscribed FBG of length 3 mm and is etched for a length of 40 mm to facilitate coiling the eFBG during fabrication. The soft contact lens was fabricated using flexible thin film technology with a transparent and flexible etched Fiber Bragg Grating (eFBG) integrated within flexible polydimethylsiloxane (PDMS) for sensing corneal deformations brought about by IOP variations. Experimental studies on the bionic eyeball model show that the Bragg wavelength shift is highly linear (r2 = 0.9694), with a very good sensitivity of 49.243 pm/mmHg in the IOP pressure range of 0 to 50 mmHg. Due to its ease of fabricating, simplicity of design, and ability to continuously measure pressure with good repeatability and stability, the proposed sensor thus offers a potential solution for IOP monitoring.

Smart Contact Lenses-A Step towards Non-Invasive Continuous Eye Health Monitoring.

According to the age-old adage, while eyes are often considered the gateway to the soul, they might also provide insights into a more pragmatic aspect of our health: blood sugar levels. This potential breakthrough could be realized through the development of smart contact lenses (SCLs). Although contact lenses were first developed for eyesight correction, new uses have recently become available. In the near future, it might be possible to monitor a variety of ocular and systemic disorders using contact lens sensors. Within the realm of glaucoma, SCLs present a novel prospect, offering a potentially superior avenue compared to traditional management techniques. These lenses introduce the possibility of non-invasive and continuous monitoring of intraocular pressure (IOP) while also enabling the personalized administration of medication as and when needed. This convergence holds great promise for advancing glaucoma care. In this review, recent developments in SCLs, including their potential applications, such as IOP and glucose monitoring, are briefly discussed.

Current Innovations in Intraocular Pressure Monitoring Biosensors for Diagnosis and Treatment of Glaucoma—Novel Strategies and Future Perspectives

Biosensors are devices that quantify biologically significant information required for diverse applications, such as disease diagnosis, food safety, drug discovery and detection of environmental pollutants. Recent advancements in microfluidics, nanotechnology and electronics have led to the development of novel implantable and wearable biosensors for the expedient monitoring of diseases such as diabetes, glaucoma and cancer. Glaucoma is an ocular disease which ranks as the second leading cause for loss of vision. It is characterized by the increase in intraocular pressure (IOP) in human eyes, which results in irreversible blindness. Currently, the reduction of IOP is the only treatment used to manage glaucoma. However, the success rate of medicines used to treat glaucoma is quite minimal due to their curbed bioavailability and reduced therapeutic efficacy. The drugs must pass through various barriers to reach the intraocular space, which in turn serves as a major challenge in glaucoma treatment. Rapid progress has been observed in nano-drug delivery systems for the early diagnosis and prompt therapy of ocular diseases. This review gives a deep insight into the current advancements in the field of nanotechnology for detecting and treating glaucoma, as well as for the continuous monitoring of IOP. Various nanotechnology-based achievements, such as nanoparticle/nanofiber-based contact lenses and biosensors that can efficiently monitor IOP for the efficient detection of glaucoma, are also discussed.

Miniaturization and modeling of a folded beam-based microelectromechanical intraocular pressure sensor

This paper describes the design and detailed analysis of a microelectromechanical system (MEMS) capacitive pressure sensor consisting of nested folded beam suspensions and variously shaped diaphragms that can be used as a part of an LC tank implant circuit for biomedical pressure sensing applications, designed specifically for continuous intraocular pressure (IOP) monitoring in glaucoma patients. The pressure sensor has been designed to measure pressures within the IOP sensor range of 0–8000 Pa. This paper aims to reduce the size of the sensor in comparison to previous research. Significant benefits of miniaturization include requiring less energy, being lightweight, being inexpensive, and having minimal impact on the objects being detected. The MEMS implantable pressure sensor for continuous monitoring of IOP would prevent the progression of the disease, and these tiny devices could alleviate patients’ suffering. Microbeams are likely the most widely utilized structural element in MEMS. This design adds nested folded beam suspensions to the diaphragm, which reduces the diaphragm’s residual tension and rigidity; as a result, the device’s dimension is smaller than the diaphragm without flexible beams (previous work). Due to the reduced rigidity, nested folded beam suspensions can also enhance sensitivity. Finally, the central deflection of the diaphragm will be determined under uniform external pressure. Using COMSOL/Multiphysics and SolidWorks, the design and simulation of pressure sensors have been accomplished. The outcomes reveal that the capacitive pressure sensor with nested folded beam suspensions and the rectangular diaphragm is better suited for measuring IOP, and its dimensions are also smaller than those of previous works ().

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.

EYEMATE-SC Trial: Twelve-Month Safety, Performance, and Accuracy of a Suprachoroidal Sensor for Telemetric Measurement of Intraocular Pressure

Measuring and controlling intraocular pressure (IOP) provide the foundation for glaucoma treatment. Self-tonometry has been proposed as an alternative to measure IOP throughout the entire day better. The novel EYEMATE-SC sensor (Implandata) is implanted in the suprachoroidal space to enable contactless continual IOP monitoring. The aim of the present study was to investigate the 1-year safety, performance, and accuracy of the EYEMATE-SC in patients with primary open-angle glaucoma undergoing simultaneous nonpenetrating glaucoma surgery (NPGS). Prospective, multicenter, open-label, single-arm, interventional clinical trial. Twenty-four eyes of 24 patients with primary open-angle glaucoma who were due to undergo NPGS (canaloplasty or deep sclerectomy). An EYEMATE-SC sensor was implanted during NPGS. Goldmann applanation tonometry (GAT) measurements were compared with the sensors' IOP measurements at all postoperative visits through 12 months. Device position and adverse events. Fifteen eyes underwent canaloplasty, and 9 underwent deep sclerectomy. Successful implantation of the sensor was achieved in all eyes with no reported intraoperative difficulties. Through the 12-month follow-up, no device migration, dislocation, or serious device-related complications were recorded. A total of 536 EYEMATE-SC measurements were pairwise included in the IOP agreement analysis. The overall mean difference between GAT and EYEMATE-SC measurements was 0.8 mmHg (95% confidence interval [CI] of the limits of agreement [LoA], -5.1 to 6.7 mmHg). The agreement gradually improved, and from 3 months after surgery until the end of the follow-up, the mean difference was -0.2 mmHg (95% CI of LoA, -4.6 to 4.2 mmHg) over a total of 264 EYEMATE-SC measurements, and 100% of measurements were within ±5 mmHg of GAT. The EYEMATE-SC sensor was safe and well tolerated through 12 months. Moreover, it allowed accurate, continuous IOP monitoring. Proprietary or commercial disclosure may be found after the references.

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.

A New Contact Lens Sensor System for Continuous Intraocular Pressure Monitoring: Evaluation of Safety and Tolerability.

To assess the safety and tolerability of a new contact lens sensor (CLS) system for continuous 3- and 24-hr intraocular pressure (IOP) monitoring in human eyes. Twenty-five subjects were recruited for 3-hr IOP measurement by CLS. Corneal fluorescein staining (CFS) scores were evaluated before and after measurement. Then, 30 participants (10 normal subjects and 20 glaucoma patients) were recruited for 24-hr IOP monitoring. Ocular surface disease index (OSDI) was assessed before and one day after measurement. Contact lens dry eye questionnaire-8 was assessed immediately after measurement. Visual analog scale of discomfort was measured before, immediately after, and one day after measurement. Best-corrected visual acuity (BCVA), tear break-up time (TBUT), and CFS were assessed before, immediately after, and 1 day after measurement. All participants completed 3- or 24-hr IOP measurement by CLS. Corneal fluorescein staining increased from 0.6±0.7 to 2.4±1.5 after 3-hr IOP measurement ( P <0.001). For participants undergoing 24-hr IOP monitoring, OSDI increased from 9.1±9.7 to 18.0±12.4 ( P =0.001). CLDEQ-8 score was 11.6±5.8. Visual analog scale increased from 11.1±14.2 to 35.2±21.8 after measurement ( P <0.001) and decreased to 26.7±18.4 one day later ( P <0.001 compared with baseline). BCVA decreased from 1.0±0.01 to 0.8±0.1 ( P <0.001) and returned to 0.9±0.1 after one day ( P <0.001 compared with baseline). TBUT decreased from 5.1±3.9 to 2.6±1.5 s ( P =0.001) and returned to 4.8±2.5 s ( P =0.465 compared with baseline). Corneal fluorescein staining increased from 0.7±0.9 to 4.3±0.8 ( P <0.001) and dropped to 0.8±0.7 ( P =0.599 compared with baseline). No significant difference was found for all variations of indicators between normal subjects and glaucoma patients ( P >0.1 for all comparisons). The CLS shows a great potential for a safe and tolerable 24-hr IOP monitoring in normal subjects and glaucoma patients. Clinical attention to the worsening signs and symptoms after measurement is required.

Real-Time Monitoring of Intraocular Pressure in Glaucoma Patients Using Wearable Mobile Medicine Devices.

Glaucoma is caused by excessive aqueous humor in the eye, resulting in a continuous or intermittent increase of intraocular pressure, which exceeds the tolerance of the eyeball and damages the optic nerve. Existing treatments for glaucoma do not work well or have significant side effects. Intraocular pressure signal is a very important physiological signal that needs real-time and accurate monitoring in glaucoma patients, especially in severe glaucoma patients. Therefore, long-term, real-time, and accurate monitoring of intraocular pressure is of great significance for the diagnosis and treatment of glaucoma patients. The use of wearable devices for real-time ocular diagnosis and treatment of glaucoma patients is an effective approach. However, the current commonly used intraocular pressure measurement and monitoring technology is difficult to meet the diagnosis and monitoring needs of glaucoma patients in terms of size, measurement accuracy, power consumption, and intelligence. Therefore, facing the needs of glaucoma disease treatment, this topic studies an implantable flexible intraocular pressure sensor for long-term continuous monitoring of intraocular pressure in glaucoma patients and mainly focuses on the working principle, structural design, process fabrication, measurement and control system, characterization, and performance test of the intraocular pressure sensor. It is of great significance for personalized and accurate treatment of glaucoma patients.

A Meta-Analysis of Wearable Contact Lenses for Medical Applications: Role of Electrospun Fiber for Drug Delivery.

In recent years, wearable contact lenses for medical applications have attracted significant attention, as they enable continuous real-time recording of physiological information via active and noninvasive measurements. These devices play a vital role in continuous monitoring of intraocular pressure (IOP), noninvasive glucose monitoring in diabetes patients, drug delivery for the treatment of ocular illnesses, and colorblindness treatment. In specific, this class of medical devices is rapidly advancing in the area of drug loading and ocular drug release through incorporation of electrospun fibers. The electrospun fiber matrices offer a high surface area, controlled morphology, wettability, biocompatibility, and tunable porosity, which are highly desirable for controlled drug release. This article provides an overview of the advances of contact lens devices in medical applications with a focus on four main applications of these soft wearable devices: (i) IOP measurement and monitoring, (ii) glucose detection, (iii) ocular drug delivery, and (iv) colorblindness treatment. For each category and application, significant challenges and shortcomings of the current devices are thoroughly discussed, and new areas of opportunity are suggested. We also emphasize the role of electrospun fibers, their fabrication methods along with their characteristics, and the integration of diverse fiber types within the structure of the wearable contact lenses for efficient drug loading, in addition to controlled and sustained drug release. This review article also presents relevant statistics on the evolution of medical contact lenses over the last two decades, their strengths, and the future avenues for making the essential transition from clinical trials to real-world applications.

Notched-ring structured microfluidic contact lens for intraocular pressure monitoring

Microfluidic contact lenses (MCLs) for continuous intraocular pressure (IOP) monitoring are promising devices for the diagnosis and management of glaucoma. Here, we present an ultra-sensitive and cost-effective MCL for IOP monitoring. A folding method that allows 2D-to-3D transformation of a planar microchannel is introduced. An ultra-sensitive serpentine microchannel of notched-ring configuration is designed in coordination with the folding method. The optimization of the microchannel geometry is performed through numerical simulations and experiments. The performance of the device is evaluated using a hemispherical silicone model eye. The sensitivity of the MCL reaches up to 0.825°/μl, which clearly exceeds the existing MCLs. Moreover, stair-case and cyclical tests are performed to confirm the device's recoverability and repeatability. These results prove that the proposed MCL is a suitable selection for intraocular pressure monitoring.

Wearable electronic devices for glaucoma monitoring and therapy

Glaucoma is a leading cause of irreversible blindness worldwide, which is estimated to affect approximately 112 million people by 2040. Elevated intraocular pressure (IOP) is the most important risk factor for glaucoma, as well as the primary target for the treatment. Current therapies aim at IOP reduction to prevent the disease progression. The accurate and real-time measurement of IOP is therefore critical to evaluate treatment response and guide medical decisions. However, IOP fluctuates throughout the 24-hour cycle with different patterns from day to day in the same individual and also different patterns among individuals. The current clinical practice typically captures a single IOP measurement during “in-office hours”, and this is insufficient for disease monitoring. With the development of wearable electronic devices, a variety of IOP monitoring devices provide a unique potential for continuous IOP monitoring. In addition to IOP monitoring for glaucoma management, this mini-review also summarizes novel drug delivery devices for treating glaucoma. Because certain types of glaucoma do not show elevated IOP, we also discuss the potential to incorporate biomarker detection with IOP measurement for more accurate and reliable glaucoma diagnostics and therapies.

How to Measure Intraocular Pressure: An Updated Review of Various Tonometers.

Intraocular pressure (IOP) is an important measurement that needs to be taken during ophthalmic examinations, especially in ocular hypertension subjects, glaucoma patients and in patients with risk factors for developing glaucoma. The gold standard technique in measuring IOP is still Goldmann applanation tonometry (GAT); however, this procedure requires local anesthetics, can be difficult in patients with scarce compliance, surgical patients and children, and is influenced by several corneal parameters. Numerous tonometers have been proposed in the past to address the problems related to GAT. The authors review the various devices currently in use for the measurement of intraocular pressure (IOP), highlighting the main advantages and limits of the various tools. The continuous monitoring of IOP, which is still under evaluation, will be an important step for a more complete and reliable management of patients affected by glaucoma.

Recent progress of continuous intraocular pressure monitoring

AbstractGlaucoma, a chronic optic neuropathy, is the leading cause of irreversible blindness in the world. Elevated intraocular pressure (IOP) has been considered to be the major contributor to glaucoma for a long time and is currently proved to be the only modifiable risk factor for the progression of optic neuropathy. IOP fluctuates throughout the day with a circadian rhythm change and is affected by body gesture changes. Moreover, the IOP spike usually occurs at night or in the early morning. Therefore, the current clinical practice of single and static measurements of IOP during office hours is not conducive to the early diagnosis and treatment of glaucoma. This review focuses on current advances in implantable and noninvasive IOP sensors for obtaining 24‐hour continuous IOP profiles. The content summarizes and classifies IOP sensors based on their working principles and provides representative examples of the sensors for IOP monitoring. Finally, the review further analyzes the challenges of current IOP sensors for clinical practice and puts forward the prospect of IOP sensors in the future.

An Ultrasensitive Contact Lens Sensor Based On Self‐Assembly Graphene For Continuous Intraocular Pressure Monitoring

AbstractElevated intraocular pressure (IOP) is the leading cause of glaucoma. As glaucoma is an irreversible neurological eye disease, it is urgent to realize timely and accurate IOP detection for diagnostic and therapeutic purposes. Here, a contact lens sensor for continuous IOP monitoring using self‐assembly graphene (SAG), is developed. The combination of face‐to‐face water transfer printing and micro‐electromechanical systems technology can realize the batch preparation of such a sensor. The sensor has good light transmittance and temperature stability. It exhibits an ultra‐high IOP sensitivity of 1.0164 mV mm Hg−1 on a silicone eye, and 3.166 mV mm Hg−1 in vitro on the porcine eye with remarkable linearity. The sensitivity of the proposed sensor is high enough to be read by a commercial radio frequency identification read–write system for continuous wireless monitoring of IOP. Furthermore, the as‐prepared sensor can work as normal for 24 h in phosphate buffer saline.

Smart Contact Lenses with a Transparent Silver Nanowire Strain Sensor for Continuous Intraocular Pressure Monitoring.

Continuous intraocular pressure (IOP) monitoring can provide a paradigm shift in the management of patients with glaucoma as a facile alternative to conventional diagnostic methods. However, the low sensitivity and functional instability of current IOP sensors have limited their clinical utility in the management of glaucoma. Here, we have developed a smart contact lens integrated with a transparent silver nanowire IOP strain sensor and wireless circuits for noninvasive, continuous IOP monitoring. After confirming the robust stability of the IOP sensor within the smart contact lens in the presence of tears and repeated eyelid blink model cycles, we were able to monitor IOP changes on polydimethylsiloxane model eyes in vitro. In vivo tests demonstrated that our fully integrated wireless smart contact lens could successfully monitor the change in IOP in living rabbit eyes, which was clearly validated by the conventional invasive tonometer IOP test. Taken together, we could confirm the feasibility of our smart contact lens as a noninvasive platform for continuous IOP monitoring of glaucoma patients.

High-sensitivity liquid-metal-based contact lens sensor for continuous intraocular pressure monitoring

Intraocular pressure (IOP) is a crucial physiological indicator for the diagnosis and treatment of glaucoma. The current infrequent IOP measurement during an office visit is insufficient to characterize the symptoms. Here, an LC resonator strain sensor in a contact lens, composed of a stretchable inductance coil using liquid metal and a chip capacitor, was developed for real-time IOP monitoring. The lens sensor was operated on the basis of ‘mechanical-electrical’ principle. The rising IOP will increase the curvature radius of the cornea and stretch the inductance coils through the cornea and tear film, leading to a decrease in resonant frequency. The theoretical model of the whole process has been established and explored. The sensor has been scientifically designed and fabricated to be ultra-soft, comfortable, safe without leakage and has a stable signal. The sensor was calibrated on two silicone rubber model eyeballs, respectively, showing linear and stable responses. An experiment on porcine eyes in vitro was conducted. The sensor can track IOP changes and shows much higher sensitivity than the current mainstream lens sensors, which is even an order of magnitude higher than the existing inductive sensor. The high-sensitivity and ultra-flexible liquid-metal-based lens sensor is a promising approach for 24 h continuous IOP monitoring in clinics.

Wearable Contact Lens Sensor for Non-invasive Continuous Monitoring of Intraocular Pressure.

Intraocular pressure (IOP) is an essential indicator of the diagnosis and treatment of glaucoma. IOP has an apparent physiological rhythm, and it often reaches its peak value at night. To avoid missing the peak value at night and sample the entire rhythm cycle, the continuous monitoring of IOP is urgently needed. A wearable contact lens IOP sensor based on a platinum (Pt) strain gauge is fabricated by the micro-electro-mechanical (MEMS) process. The structure and parameters of the strain gauge are optimized to improve the sensitivity and temperature stability. Tests on an eyeball model indicate that the IOP sensor has a high sensitivity of 289.5 μV/mmHg and excellent dynamic cycling performance at different speeds of IOP variation. The temperature drift coefficient of the sensor is 33.4 μV/°C. The non-invasive IOP sensor proposed in this report exhibits high sensitivity and satisfactory stability, promising a potential in continuous IOP monitoring.