Article

# Notched-ring structured microfluidic contact lens for intraocular pressure monitoring

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## Abstract

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.

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Intraocular pressure (IOP) is a primary indicator of glaucoma, but measurements from a single visit to the clinic miss the peak IOP that may occur at night during sleep. A soft chipless contact lens sensor that allows the IOP to be monitored throughout the day and at night is developed in this study. A resonance circuit composed of a thin film capacitor coupled with a sensing coil that can sense corneal curvature deformation is designed, fabricated and embedded into a soft contact lens. The resonance frequency of the sensor is designed to vary with the lens curvature as it changes with the IOP. The frequency responses and the ability of the sensor to track IOP cycles were tested using a silicone rubber model eye. The results showed that the sensor has excellent linearity with a frequency response of ∼8 kHz/mmHg, and the sensor can accurately track fluctuating IOP. These results showed that the chipless contact lens sensor can potentially be used to monitor IOP to improve diagnosis accuracy and treatment of glaucoma.
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The tear film is a valuable diagnostic fluid for a continuous, minimally invasive surveillance of health conditions in a patient. We developed an electronic enzymatic l-lactate sensor on a polymer substrate molded into contact lens shape for potential in situ monitoring of l-lactate levels in tear fluid. The platinum sensing structures were functionalized by cross-linkage of lactate oxidase with glutaraldehyde and bovine serum albumin, and coated with medical grade polyurethane. Different approaches for the suppression of interfering species present in the tear film were evaluated. The sensors show a quick response time of 35 s, an average sensitivity of ∼53 μA mM−1 cm−2 within their linear range, and sufficient resolution within the physiological range of lactate concentrations. A dual sensor design was found appropriate for the suppression of interfering signals. The sensors are functional at temperatures comparable to those at the surface of the eye, and their response is stable for up to 24 h.
Article
This paper presents the first biocompatible, unpowered, micromachined pressure sensor for intraocular pressure (IOP) sensing. This device is designed for implantation in the eye so that IOP can be faithfully measured externally. It features a parylene-based high-aspect-ratio spiral-tube structure fabricated using a buried-channel process. This passive sensor requires no power from other physical (i.e. electrical and/or magnetic) domains and registers pressure variations by changes of a mechanical in-plane spiral rotation that can be gauged by direct and convenient optical observation. The fabricated device has been tested in various media, and a 1 mm-radius device with a 10-turn spiral has successfully demonstrated continuous spiral rotation when immersed in liquids, with 0.22°/mmHg sensitivity in isopropyl alcohol (IPA) and 0.13°/mmHg sensitivity in water. This pressure sensing technology is proposed as a convenient method to monitor in situ IOP in glaucoma patients and to facilitate treatment and scientific study of the disease.
Article
To determine the statistically normal range of corneal Young's modulus in young healthy eyes in vivo, and to establish if this variation has a clinically significant influence on intraocular pressure (IOP) measurement using applanation tonometry. Central corneal curvature, central corneal thickness (CCT), and applanation IOP (Goldmann tonometer) were measured using standard clinical techniques in one eye of 100 normal human subjects (22.0 +/- 2.9 years) in vivo. The Orssengo-Pye algorithm was used to calculate the corneal Young's modulus of these experimental subjects, and to produce a theoretical model of potential errors in Goldmann applanation tonometry estimates of IOP due to variations of Young's modulus and CCT. Corneal Young's modulus was 0.29 +/- 0.06 MPa [95% confidence interval (CI) 0.17 to 0.40 MPa]. According to the Orssengo-Pye model, the relationship between Young's modulus and the error in applanation IOP is linear; the slope was 23 mm Hg per MPa. An increase from the minimum to the maximum value of the calculated limits of agreement (95% CI) of Young's modulus caused a variation in applanation IOP of 5.35 mm Hg. The anticipated error at the extremes of the limits of agreement (95% CI) of CCT was similar at 4.67 mm Hg. Physiological variations in corneal Young's modulus may cause clinically significant errors in Goldmann applanation tonometry estimates of IOP.
Article
To test the hypothesis that blunt trauma shockwave propagation may cause macular and peripheral retinal lesions, regardless of the presence of vitreous. The study was prompted by the observation of macular hole after an inadvertent BB shot in a previously vitrectomized eye. The computational model was generated from generic eye geometry. Numeric simulations were performed with explicit finite element code. Simple constitutive modeling for soft tissues was used, and model parameters were calibrated on available experimental data by means of a reverse-engineering approach. Pressure, strain, and strain rates were calculated in vitreous- and aqueous-filled eyes. The paired t-test was used for statistical analysis with a 0.05 significance level. Pressure at the retinal surface ranged between -1 and +1.8 MPa at the macula. Vitreous-filled eyes showed significantly lower pressures at the macula during the compression phase (P < 0.0001) and at the vitreous base during the rebound phase (P = 0.04). Multiaxial strain reached 20% and 25% at the macula and vitreous base, whereas the strain rate reached 40,000 and 50,000 seconds(-1), respectively. Both strain and strain rates at the macula, vitreous base, and equator reached lower values in the vitreous- compared with the aqueous-filled eyes (P < 0.001). Calculated pressures, strain, and strain rate levels were several orders of magnitude higher than the retina tensile strength and load-carrying capability reported in the literature. Vitreous traction may not be responsible for blunt trauma-associated retinal lesions and can actually damp shockwaves significantly. Negative pressures associated with multiaxial strain and high strain rates can tear and detach the retina. Differential retinal elasticity may explain the higher tendency toward tearing the macula and vitreous base.
Article
Assessment on enucleated pig eyes of a novel and minimally invasive method for the continuous monitoring of intraocular pressure (IOP), based on a novel wireless contact lens sensor (CLS). The wireless CLS is a disposable silicone soft contact lens with a sensor embedded in it, allowing the wireless measurement of changes in corneal curvature induced by IOP variations. A CLS was adapted and tested on enucleated pig eyes. To demonstrate the measurement principle of the device, the enucleated pig eye was cannulated, allowing precise control of IOP. The CLS signal was then compared to the imposed IOP. First, the IOP of enucleated pig eyes was changed between 11 and 14 mmHg, simulating ocular pulsation. Then, IOP was changed with static steps of 1 mmHg between 20 and 30 mmHg to assess the reproducibility and linearity of the CLS. In both cases, measurements from the CLS and IOP showed very good correlation. A calibration graph shows that the CLS is capable of monitoring the IOP of each individual eye with a reproducibility of +/- 0.2 mmHg (95% confidence interval). The wireless CLS shows a good functionality to monitor the IOP on enucleated pig eyes. The device is placed in the same way as a soft disposable contact lens. This device would allow a minimally invasive and continuous monitoring of IOP over prolonged periods of up to 24 hr, regardless of patient activity, thus opening up new diagnostic and therapeutic methods to manage glaucoma.
Article
Twenty-three optometry students with normal corneal condition were recruited. The intraocular pressure and central corneal curvature of the right eye were measured in a sitting and a 30 degrees head-down posture. The mean (standard deviation) IOPs before and during posture change were 15.6 (2.4) mmHg and 22.1 (2.3) mmHg respectively. This 6.5 mmHg mean rise in IOP was found to be statistically significant which is similar to the results from previous studies. The mean changes in radius of corneal curvature and the orientation of the axis of the vertical principal meridian were 0.02 mm (SD 0.025 mm) and 2.4 degrees (SD 10.4 degrees) respectively. No significant variation was demonstrated on these keratometric results due to the 30 degrees head-down posture. The maximum change in radius of curvature was only 0.055 mm for one subject. Perhaps this amount of pressure rise was not sufficient enough to distort the corneal surface centrally. Another possibility could be an even distribution of the elevated pressure around the cornea, or the distribution of pressure is not even but could not be revealed by a conventional keratometer.
Article
To present a novel and minimally invasive approach to intraocular pressure (IOP) monitoring based on a sensing contact lens. The key element of this measurement method is a soft contact lens with an embedded microfabricated strain gauge allowing the measurement of changes in corneal curvature correlated to variations in IOP. A prototype of this sensing contact lens was adapted and tested on enucleated porcine eyes. To verify the measurement principle of the device, the posterior chamber of the pig eyes was cannulated and connected to a syringe pump and a pressure sensor for precise control of IOP. The measurements of the contact lens were then compared to the ones from the pressure sensor, while pressure variations were induced through the cannula. Enucleated porcine eyes were stimulated with increasing and decreasing ramps of IOP. Measurements from the sensing contact lens and from the pressure sensor showed very good correlation, proving the high potential of this new measurement principle. In this study, a typical signal from the sensing contact lens obtained during the experiments is presented and discussed. The sensing contact lens shows the potential for continuously monitoring IOP in enucleated porcine eyes. The ultimate step will be the validation of the system and the reproducibility of results in humans. The device is placed in the same way as a corrective contact lens, no anesthesia is required, and vision remains almost unimpaired. This device would allow minimally invasive IOP monitoring over prolonged periods, regardless of the patient's position and activity, thus opening up new diagnostic and therapeutic methods for the management of glaucoma.
• T Rossi
• B Boccassini
• L Esposito
• M Iossa
• A Ruggiero
• G Tamburrelli
• N Bonora
T. Rossi, B. Boccassini, L. Esposito, M. Iossa, A. Ruggiero, G. Tamburrelli, and N. Bonora, Invest. Ophthalmol. Visual Sci. 52, 3994 (2011).