Title: Contact lens device for the continuous monitoring of intraocular pressure
Funder: Department of Health (England)

Abstract: Research Plan Survey of relevant IP has been conducted at the start of our work on the new device, and has been regularly updated (see Annex 5 for more information). Existing IP can be put in 3 groups: 1. Devices that employ pressure transducers which need to be surgically implanted inside the eye or within the thickness of the cornea. These systems would not be expected to be used except in cases where surgical intervention is required for another reason. 2. Devices that employ non-invasive instruments bearing against the sclera, so as to avoid affecting the user's vision. These systems, which rely on indenting the stiff sclera, are bulky and uncomfortable to wear. 3. Devices that incorporate pressure transducers placed in a corneal contact lens. These devices vary widely in design. They include one that uses a lens' flat back surface, which changes the refractive power of the eye and affects the patient's vision while wearing it (Waters, 1990). Another device uses a contact lens with a built in pressure transducer, which requires manual activation by a plunger, and is therefore not suitable for continuous use (Fleischman, 2007). A more promising device was designed by Leonardi (2004) and is being developed by Sensimed under the commercial name “Triggerfish”. The device incorporates a contact lens fitted with a circumferential strain gauge that detects topography changes caused by IOP variations. The system uses pure silicone, which sticks to the corneal epithelium, monitors the profile of IOP changes rather than absolute IOP values and is expensive (€500 for the lens component). Further, the device does not consider the natural variation in corneal thickness, curvature and age, and their effects on corneal stiffness, and as a result, the system is likely to require calibration for each patient. None of these systems is available commercially, although the Triggerfish is expected to appear on the market in 2011. Aims The project's business plan has an integrated programme of activities designed to achieve the following key deliverables:• Optimise design of device to magnify pressure signals, make signals independent of variations in eyelid pressure and tear film quality and improve compatibility with mass production techniques• Remove need for calibration for each patient by eliminating design sensitivity to variations in stiffness parameters such as corneal thickness and age• Produce advanced working prototypes of the device suitable for use in clinical studies and marketing• Obtain MHRA approval for using the device in clinical studies and as a pre-requisite to obtaining CE marking• Seek patients' views on the device through the involvement of the International Glaucoma Association• Protect new technology with appropriate patent applications• Validate the device experimentally through tests on human donor corneas to assess the accuracy, stability and repeatability of the IOP measurements• Conduct a series of initial clinical validations to assess the reliability of the contact lens device and suitability for extended use The business plan is composed of three inter-linked research and development work packages. The work packages concentrate on (1) design optimisation of the contact lens component, (2) holistic development of device, and (3) experimental and clinical validation. While Liverpool will be mainly responsible for WP1, UltraVision will conduct WP2, and Liverpool and Moorfields will share responsibility for WP3. WP1: Design optimisation of contact lensThe FPD1 project concentrated on assessing the feasibility of the contact lens design and whether it can provide reliable and repeatable IOP signals. With focus remaining on the contact lens and its pressure sensors, the design will be optimised with particular attention given to the following objectives: 1-1 Strong IOP signalsA parametric study based on nonlinear finite element analysis will be conducted in which variations will be introduced into the detailing of the sensor zone (the protruded part and the rigid ring) and its location on the cornea. Attention will be given to both the strength and repeatability of IOP signals. 1-2 Low sensitivity to variations in eyelid pressureThe device relies on eyelid pressure during blinking to produce micro-indents of the cornea and trigger IOP measurements. Design optimisation will ensure low sensitivity of IOP measurements to the value of eyelid pressure, which is known to reduce with age, and assess technology developed for patients with exceptionally low eyelid pressure. 1-3 Low sensitivity to quality of tear filmTear film produces surface tension that brings the lens into contact with corneal surface and restricts movement with blinks. The study aims to achieve improved lens topography and thickness distribution to reduce the sensitivity of the device to tear film quality and improve ability to maintain the lens intended position. 1-4 Influence of biointeractions at the lens interfaceThe comfort of the lens for the wearer and the ability to maintain the health of the cornea will be dependent on the material characteristics of the lens material. Important considerations are the surface wettability, oxygen diffusion and the mechanical properties of the materials. One option may be to consider surface modification of the lens material to optimise wettability. The biointeractions between the tear film and the contact lens surface will be studied and their influence on the quality of the tear film analysed. Methods of modifying the surface properties of the lens material to minimise these interfacial reactions will be investigated. 1-5 Low sensitivity to variations in corneal stiffnessIn order to avoid the need for calibration for every patient, technology has been developed to provide a direct measure of corneal stiffness and its effect on IOP measurements. The technology is based on using a second contact lens with a different profile, producing different corneal response to indentation. By numerically analysing the indentation action with both lens profiles, the level of corneal stiffness will be determined, and its effect removed from IOP measurements. WP2: Holistic development of deviceThis WP will adopt a holistic approach to device development and will seek to combine the components to produce a safe, reliable and efficient commercial product. 2-1 Compatibility with manufacturing techniquesClose interaction with component manufacturers will be maintained to ensure the designs are suitable for mass production. This will be necessary to reduce the cost, improve the geometrical control of components and enable the automated assembly of the components within a strictly clean environment with little or no human intervention. 2-2 Design of magnetic field and telemetry systemThe device relies for wireless communication on mutual inductance to magnetically couple a respondent coil placed on the contact lens and an exciter coil placed in close proximity of the lens. This technology will be optimised to ensure the stability of readings with practical variations in distance between the coils, and with small lateral misalignments. The optimisation will include circuit design followed by experimental validation. 2-3 Development of control softwareA software program will be built in VB to enable user-friendly interaction with the device, collection and storage of IOP measurements, filtering out of data noise, analysis of data to extract IOP variations and ocular pulse amplitude, application of pressure corrections based on a stiffness estimate, determination of when device is incorrectly used and download of data to a computer. Following validation, the software will be transferred onto a Field-Programmable Gate Array chip and used in the external controller. 2-4 Design of external controllerThe external controller will be designed to embody the hardware components necessary to power the device, collect and record the IOP measurements, run the control software, communicate with an external computer and display status messages to the user. The instrument will be optimised to be small and light enough to fit on the arms of glasses or be supported on the side of the user's face using non allergic medical tape. 2-5 MHRA approvalThe device will be registered with the MHRA prior to commencement of clinical validation and as a pre-requisite to CE marking. 2-6 Commercialisation planA commercialisation plan will be developed by UltraVision with support from MEH and Liverpool to guide the future marketing of the device and to ensure the project achieves its main objective; to offer greater diagnostic capability and more appropriate management plans at a reduced overall cost to the NHS. This will be assisted by a mid-term commercial review to ensure product remains on track to stay below the target price of £25. A market research exercise will take place within this task to quantify market opportunities, potential marketing partners and maximum price tag. Compilation of technical material suitable for marketing the device and inclusion within sale packages will be undertaken. WP3: ValidationFollowing design optimisation, the device will undergo experimental and clinical validation to assess its performance and in particular ability to produce correct and repeatable results, and tolerance to imperfect working conditions. 3-1 Experimental validationExperimental validation, involving at least 18 human donor corneas, will be conducted to assess the accuracy of IOP measurements made by the device. The corneas will be subjected to known levels of IOP within tightly-controlled experimental conditions of humidity and temperature, while using contact lens prototypes to produce IOP measurements. The differences between the applied and measured IOP values will help assess the accuracy of the device and its dependence on corneal mechanical stiffness, which will also be measured experimentally. The tests will require modifications in our test rig to enable simulation of the ocular pulse amplitude and the application of eyelid pressure on corneal surface. Ethical approval to use corneal specimens in research will be obtained before commencement of study. 3-2 Clinical proof of principleTwo clinical studies, involving 12 and 40 participants, respectively, will be conducted at Moorfields Eye Hospital (MEH) and Royal Liverpool University Hospital, and approved by the research ethics committees of the two hospitals. The studies will assess the comfort of use over 24hr and the lens fitting. They will check for corneal staining and stromal swelling. Comparisons will be made between the contact lens IOP measurements and the measurements of the Goldmann Applanation Tonometer - the reference standard in tonometry. The studies will provide initial clinical assessment and analysis of glaucoma management in respect to continuous IOP measurement. Informed consent will be obtained from participants before enrolment in the studies. 3-3 Patients' viewsThe IGA, with assistance from the two hospitals involved, will take an active role in seeking patients' views on the device. The IGA will use its network of patient groups to seek views on the comfort of use over a 24hr period, ease of wear and removal of contact lens, need for clinic visits to install contact lens, effect of rigid ring on field of vision during normal day activities such as driving, reading, using computers, etc, and ease of use of external controller and control software. The exercise will be guided by the initial results obtained from the MEH and RLUH clinical studies. Benefit Routine practice permits only measurement of IOP over a few minutes, two to three times a year at clinic visits. As a result the major risk factor for glaucoma is poorly characterised since IOP varies considerably due to changes in posture and physiologic state, and during sleep and physical effort. While technological advances in this field have managed to obtain accurate IOP measurements (through consideration of the effects of corneal stiffness in the Dynamic Contour Tonometer) and develop reliable non-contact methods (using for example the Ocular Response Analyzer and the Pulsair), they did not address the need for continuous monitoring. In a review article by James Brandt in 2007 on tonometry and glaucoma risk, it was concluded that “focusing on improving the accuracy of an inherently flawed and random measurement is unlikely to improve the care of our patients. We need to focus our efforts on 24-h monitoring [and] self-monitoring”. The proposed device addresses this need and intends to provide sufficient information on IOP fluctuation and peak values. It seeks to improve the assessment of risk for vision loss and the assessment of treatment effects, so that patients can be more appropriately managed. Using the device is expected to lead to less glaucomatous vision loss and reduced glaucoma-related loss of quality of life as a result of better-targeted treatment. The device is also likely to result in an improved engagement of the patient in his/her care, as monitoring continues outside the clinic, with possible better adherence to treatments.


Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES
Health categories: EYE