Biomedical Microsystems Prof. Dr.-Ing. Thomas Stieglitz Lehrstuhl für Biomedizinische Mikrotechnik Raum 102-00-073 Tel.: 7471 Email: [email protected] Department of Microsystems Engineering Biomedical Microsystems Lecture 3 Diagnosis and Therapy of Glaucoma www.imtek.de/bmt Thomas Stieglitz / summer term 2016 / lecture 3 slide 2 Outline • Glaucoma: description of the desease • Anatomy of the eye • Diagnosis of glaucoma • Treatment of glaucoma • Measurement of intraocular pressure • Summary www.imtek.de/bmt Thomas Stieglitz / summer term 2016 / lecture 3 slide 3 Glaucoma • Disease of the eye • Increased intraocular pressure - > 21 mmHg (2793 Pa) • Prevalence: - 2 % over 40 years (in Europe) WHO estimates over 70 mio persons worldwide • Impairment of health: - reduced blood supply in the retina damage of nerves blindness • In German: do not mistake glaucoma ("grüner Star" ) with cataract ("grauer Star") www.imtek.de/bmt Thomas Stieglitz / summer term 2016 / lecture 3 slide 4 Source: Prometheus, Kopf und Neuroanatomie, 2006 Anatomy of the eye www.imtek.de/bmt Thomas Stieglitz / summer term 2016 / lecture 3 slide 5 Source: Prometheus, Kopf und Neuroanatomie, 2006 Anatomy of the eye www.imtek.de/bmt Thomas Stieglitz / summer term 2016 / lecture 3 slide 6 Aqueous humor Iris Posterior chamber Lens Cornea Anterior chamber - 99% water - Nutrients - Proteins - Ascorbate - Glucose Source: Prometheus, Kopf und Neuroanatomie, 2006 • Thick watery substance: Fossa hyaloidea • Fills the space between lens and cornea • Provides nutrients to the lens and the corneal endothelium • Carries away waste products • Pressure maintains the convex shape of the cornea www.imtek.de/bmt Thomas Stieglitz / summer term 2016 / lecture 3 slide 7 Aqueous humor circulation • Aqueous humor www.imtek.de/bmt Thomas Stieglitz / summer term 2016 / lecture 3 Source: www.merck.com - …is secreted into the posterior chamber by the ciliary body (2,4 mm³/min) - …flows through the narrow cleft between lens and iris and the pupil into the anterior chamber - …drains the eye via the trabecular meshwork, the Schlemm’s canal and finally the episcleral veins (blood system) slide 8 Pathophysiology in glaucoma - Source: Prometheus, Kopf und Neuroanatomie, 2006 • Aqueous humor does not properly drain (i.e. not over production of aqueous humor) blocking of the cleft, between iris and lens blocking of the trabecular meshwork - • Possible reasons - Deposition of hyaline material or proteins (corticosteroids) Injury and cicatrization of the trabecular meshwork Diabetes mellitus - www.imtek.de/bmt Thomas Stieglitz / summer term 2016 / lecture 3 slide 9 Pathophysiology in glaucoma • Increase of intraocular pressure - normal: 15,5 ± 5,5 mmHg pathological: 22 – 80 mmHg • Circulatory disorder - insufficient supply of blood to the optical nerve degeneration of nerve fibers Field of vision • Mechanically damage of the axons due to pressure → apoptosis www.imtek.de/bmt Thomas Stieglitz / summer term 2016 / lecture 3 slide 10 Current diagnosis of glaucoma • Goldmann tonometer www.imtek.de/bmt Thomas Stieglitz / summer term 2016 / lecture 3 Source: www.ocunet.de/gfx/klinisch_glaukom5.jpg - Force applied against the eye via stick - Measurement of the force that is needed to flatten a given area (Ø 3mm) of the cornea - Single-shot measurements - Using membranes or biprismas - Best accuracy (± 1mmHg) of conventional methods slide 11 Current diagnosis of glaucoma • Pneumotonometry - Non-contact method - Measuring eye deformation by air-stream - Advantages: - No anesthesia necessary - No risk of infections - Drawbacks: - Measurement inaccuracies - Unpleasant for subject www.imtek.de/bmt Thomas Stieglitz / summer term 2016 / lecture 3 slide 12 Current diagnosis of glaucoma • Gonioscopy and goniolens Source: Wikipedia (Goldmann goniolens) - Direct or indirect iridocorneal angle measurement - Using mirrors to avoid total reflectance - Observing the anterior chamber angle (degree of opening, agglutination) - High inaccuracy! www.imtek.de/bmt Thomas Stieglitz / summer term 2016 / lecture 3 slide 13 Current treatment of glaucoma • …depends on the dimension of the glaucoma • Pharmaceutical (eye drops) - Decrease in aqueous humor production (e.g. beta blocker) Increase in drainage (e.g. adrenalin) • Laser treatment - Thermal influence on the trabecular meshwork improves the drainage Closure (obliteration) of the ciliary body • Surgical - In principle: opening of the trabecular meshwork Creation of a new drainage • Not possible to treat nerve damage www.imtek.de/bmt Thomas Stieglitz / summer term 2015 / lecture 3 slide 14 Implants to treat glaucoma • Glaucoma valves - - Silicone gum based drainage system System is implanted underneath the conjunctiva Flow tube is inserted into the anterior chamber as artificial drainage Aqueous humor flows out of the eye in a chamber called a „bleb“ Source: www.opt.pacificu.edu - • Only used after a failed pharmaceutical treatment and surgery www.imtek.de/bmt Thomas Stieglitz / summer term 2016 / lecture 3 slide 15 Glaucoma valve implant video www.imtek.de/bmt Thomas Stieglitz / summer term 2016 / lecture 3 slide 16 Drawbacks of conventional intraocular pressure measurement methods • High risk of infection • Single shot measurements - No continuous measurement of the pressure - Pressure varies within minutes or hours • Measurement is inconvenient - Partial Anesthesia - Overnight stay in hospital - Some cases require multiple measurement per day www.imtek.de/bmt Thomas Stieglitz / summer term 2016 / lecture 3 slide 17 Intraocular pressure measurement • …needs an interface to the eye • …needs a wireless data transmission system • …might be integrated into a contact lens • …might be integrated into an implant • …can be done continously in comparison to clinically available solutions www.imtek.de/bmt Thomas Stieglitz / summer term 2015 / lecture 3 slide 18 System concept for implant www.imtek.de/bmt Thomas Stieglitz / summer term 2016 / lecture 3 slide 19 S. Ullerich et al. 2001 System concept for implant • • • • Pressure sensor within artificial intraocular lens Transponder chip and micro coil are placed in the non-optical part of the lens External telemetric components integrated into spectacles Combine drainage surgery with cataract surgery www.imtek.de/bmt Thomas Stieglitz / summer term 2016 / lecture 3 slide 20 The pressure sensor • • • • www.imtek.de/bmt 2 capacitances used: pressure dependent & independent Pressure sensitivity easily adjustable via membrane size NOTE: only absolute pressure can be measured inside the eye Subtraction of external pressure Thomas Stieglitz / summer term 2016 / lecture 3 slide 21 S. Ullerich et al. 2001 Artificial lens with integrated IOP-Sensor www.imtek.de/bmt Thomas Stieglitz / summer term 2016 / lecture 3 slide 22 Biological targets specifications • • • • • wireless energy & data transmission minimum inner lens coil diameter: 7.7 mm maximum outer lens coil diameter: 10.3 mm external coil diameter: approx. 40mm transmission distance: a few centimeters • Chosen coil properties: - Transmission frequency: 14 MHz (also: 133kHz, 42 MHz) - Coil thickness: 20µm - Gap thickness: 20µm - Number of coils: 16 - Material: electroplated gold on PDMS www.imtek.de/bmt Thomas Stieglitz / summer term 2016 / lecture 3 slide 23 Dependence on viewing angle and coil distance S. Ullerich et al. 2001 • Data transmission via changing electromagnetic induction • Voltage loss due to the angle of view and the transmission distance www.imtek.de/bmt Thomas Stieglitz / summer term 2016 / lecture 3 slide 24 PDMS Packaging of the transponder S. Ullerich et al. 2001 • PDMS is biocompatible and an approved encapsulation material • Transponder output is changing after encapsulation • New calibration is needed www.imtek.de/bmt Thomas Stieglitz / summer term 2016 / lecture 3 slide 25 IOP monitoring with a contact lens • Research work at EPFL, Lausanne, CH M. Leonardi et al., IOVS 2004 - Soft contact lens (Silicone rubber) - Embedded microfabricated strain gauge (Platinum/Titanium, Polyimid) - Electrical resistance is measured www.imtek.de/bmt Thomas Stieglitz / summer term 2016 / lecture 3 slide 26 The eye with a contact lens M. Leonardi et al., IOVS 2004 • Pressure in the eye is transferred via the tear film into the contact lens with integrated sensor • Stable balanced position between the tear films (even after each blink) www.imtek.de/bmt Thomas Stieglitz / summer term 2016 / lecture 3 slide 27 In vitro test setup M. Leonardi et al., IOVS 2004 • Using of pig‘s eyes (similar to human eyes) • Calibration is needed, due to different eye sizes www.imtek.de/bmt Thomas Stieglitz / summer term 2016 / lecture 3 slide 28 In vitro test setup: results M. Leonardi et al., IOVS 2004 • Correlation between intraoperative pressure and measured values in contact lens www.imtek.de/bmt Thomas Stieglitz / summer term 2016 / lecture 3 slide 29 Contact lens calibration graph M. Leonardi et al., IOVS 2004 • Sensitivity of 8,37 µV/mmHg • Graph shows good linear fit www.imtek.de/bmt Thomas Stieglitz / summer term 2016 / lecture 3 slide 30 Conclusions: contact lens • • • • • • proof of principle work on telemetry chip for completely wireless solution no surgical intervention necessary no anaesthesia necessary disposable no resterilization disposable no lang term stability necessary, product can be replaced easily www.imtek.de/bmt Thomas Stieglitz / summer term 2016 / lecture 3 slide 31 more details: http://www.healthyaims.org/ www.imtek.de/bmt Thomas Stieglitz / summer term 2016 / lecture 3 slide 32 IOP monitoring in a contact lens • SENSIMED, CH www.imtek.de/bmt http://www.sensimed.ch/cls.html - 24 hours continuous monitoring - contact lens with resistive strain gauges, telemetry microprocessor and antenna - disposable product - no anaesthesia required - glasses or patch with receiver - monitoring during sleep is possible Thomas Stieglitz / summer term 2016 / lecture 3 slide 33 Commerzialization: Triggerfish • SENSIMED, CH SENSIMED, Triggerfish® - 24 hours continuous monitoring - contact lens with resistive strain gauges, telemetry microprocessor and antenna - disposable product - no anaesthesia required - glasses or patch with receiver - monitoring during sleep is possible More than a decade from first scientific publication to product www.imtek.de/bmt Thomas Stieglitz / summer term 2015 / lecture 3 slide 34 IOP monitoring in an intraocular lens • Commercial approach • MESOTEC, US & DE - „Der Mesograph“ Intraocular lense Wireless data transmission Accuracy: 2 mmHg Now: IMPLANDATA • ACRITEC, DE? www.imtek.de/bmt Thomas Stieglitz / summer term 2016 / lecture 3 slide 35 On the way to commerzialisation • IMPLANDATA, DE - Currently: clinical trials IMPLANDATA, EYEMATE® - Not yet an approved product - Intraocular lens with telemetry and pressure monitoring - Readout with external handheld device - In future - Closed-loop system for e.g. patient independent glaucoma therapie www.imtek.de/bmt Thomas Stieglitz / summer term 2015 / lecture 3 slide 36 Summary www.imtek.de/bmt Thomas Stieglitz / summer term 2016 / lecture 3 slide 37 Take Home Message • Glaucoma is an eye disease, whereby the intraocular pressure increases, ultimately causing blindness. • Conventional methods like Tonometry, Pneumotonometry and Gonioscopy are established, but have drawbacks e.g high risk of infection, continuous measurements not possible. • Glaucoma can be treated pharmceutically, by laser or by surgery. Glaucoma valves can be implanted for artificial drainage. • Intraocular pressure can be monitored via pressure sensors, embedded in artificial lenses, whereby the data transmission is realized by telemetry. • Intraocular pressure monitoring systems are commercially available. www.imtek.de/bmt Thomas Stieglitz / summer term 2016 / lecture 3 slide 38 Literature • Grehn, F.: Augenheilkunde. Springer Lehrbuch, Würzburg, 2002. • S. Ullerich, et al., “A Foldable Artifical Lens with an Integrated Transponder System for Measuring Intraocular Pressure”, Proc. Transducers '01, Eurosensors VX (2001) • M. Leonardi et al. "First Steps toward Noninvasive Intraocular Pressure Monitoring with a Sensing Contact Lens", Invest Ophthalmol Vis Sci 45 (9): 3113-3117 (2004) • Ahmed-Valve: http://www.ahmedvalve.com www.imtek.de/bmt Thomas Stieglitz / summer term 2016 / lecture 3 slide 39
