Smart contact lenses are no longer science fiction. In the last few years we have covered several smart contact lenses with different purposes. One of these electronic contact lenses is the Sensimed Triggerfish, a device capable of continuous measurement of the intra-ocular pressure (IOP). It is the first of its kind, since current measurements of IOP, like applanation tonometry and air-puff tonometry, can only give us the IOP at a certain moment, whereas the Triggerfish can monitor the course of the IOP throughoutthe day. As we write this, the Triggerfish is already being clinically tested.
Medgadget had the chance to interview Dr. René Goedkoop, Chief Medical Officer of Sensimed, the Swiss company responsible for the Triggerfish, and get more details about the motivation and the fascinating technology inside the device.
Stanley Darma, Medgadget: How did the idea of continuous monitoring of the intra-ocular pressure with a contact lens come to be?
Dr. René Goedkoop, CMO of Sensimed: Glaucoma is a progressive degenerative disease of the optic nerve, characterized by loss of retinal ganglion cells and its axons that ultimately leads to loss of vision and subsequent irreversible blindness. To date, reduction of IOP remains the mainstay of glaucoma treatment as it is the only proven modifiable risk factor for the development and progression of glaucoma.
IOP is commonly measured by Goldmann applanation tonometry (GAT). Limitations of GAT are characterized by indirect measurement through applanation of the central cornea, influenced by corneal factors and intra- and inter-operator variability, and the static nature of measurement. Hence tonometry only provides a snapshot of the IOP, usually taken in the sitting position during office hours. The latter is a shortcoming in light of the dynamic behavior of IOP with its circadian rhythm known to fluctuate 4-5 mmHg in healthy subjects and even more patients with glaucoma. Sleep lab studies have demonstrated that the IOP, measured every 2 hours is elevated during night in the supine position in the majority of patients with glaucoma and that IOP patterns may be specific to disease state. Sleep lab circadian IOP assessment is scarcely done for glaucoma patients given the cost and the unphysiological setting of repeated IOP measurement requiring waking up the patient during sleep.
A variety of retrospective and prospective clinical studies have demonstrated that the 24-hour IOP pattern, including number and amplitude of peaks, relationship to body position and time of day may be implicated in the pathophysiology of glaucoma, and in particular the progression thereof.
The idea of using a contact lens sensor to monitor IOP indirectly via ocular dimensional changes occurred to one of the founders and CTO of Sensimed, Matteo Leonardi, PhD as he was studying biomedical engineering at the Swiss Institute of Technology. Pursuant a meeting between students and doctors that discussed unmet medical need, Dr Leonardi became highly interested in the idea of monitoring IOP and initiated this project leading to his PhD and spun-off a start-up company. That resulted in the first CE-marked medical device, the SENSIMED Triggerfish®, consisting of a non-invasive wireless soft contact lens sensor (CLS) and a system for automated recording of IOP-related patterns for up to 24 hours. The ambulatory patient wears the device for 24 hours and assumes normal activities, including undisturbed sleep. At the end of the session, the data is transferred from the recorder to the ophthalmologist computer for analysis of the circadian IOP-related pattern.
Medgadget: Could you explain how the SENSIMED Triggerfish measures the IOP? And how do these measurements compare to the current standards of intra-ocular pressure measurements?
Dr. Goedkoop: The circular strain gauge embedded in the soft contact lens senses circumferential changes at the corneoscleral area. Relative changes in IOP are thus indirectly monitored by ocular volume changes. The output is not calibrated to mmHg today, but to an equivalent of the electric voltage (mV eq).
The CLS output consists of 288 data points over 24 hours, one data point every five minutes during a 24-hour recording. Each data point represents the median of 300 IOP-related measurements over 30 seconds, equating to a sampling frequency of 10 Hz. The software is designed to plot the 24-hour IOP pattern, whereas each data point can be inspected for eye blinks and ocular pulsation, including the systolic and diastolic peaks, the ocular pulsation amplitude, and ocular pulsation frequency as the IOP fluctuates synchronically with the heart rate.
In contrast to tonometry that measures the IOP indirectly by applying a force on the central cornea, the CLS monitors IOP indirectly by spontaneous change of the ocular volume at the corneoscleral area. The exact calibration of the CLS output to mmHg is complex, as simultaneous use of the CLS and tonometry on the same eye is not feasible, and as the relation between pressure (tonometers) and volume (CLS) is characterized both by a non-linear relationship and by the viscoelastic behavior of eye tissue.
Of benefit, the CLS does not require for an operator to apply a force to the cornea, and as the patient is not aware of the time of each recording, the measurement is both patient- and investigator-independent and yields precise and repeatable 24-hour IOP-related patterns.
The two methods are not directly comparable and do not have the same objective. The CLS provides information on IOP-related patterns that have not been seen to date. In other words, the SENSIMED Triggerfish® is complimentary to tonometry in the management of patients with glaucoma by providing information on a patient’s 24 hour day in real life.
Medgadget: The intra-ocular pressure is the only treatable risk factor in the management of glaucoma. The possibility of measuring the IOP continuously is revolutionary. How do you envision the future of glaucoma management with the SENSIMED Triggerfish?
Dr. Goedkoop: The IOP-related pattern as provided by SENSIMED Triggerfish® output is speaking to us.
As published, the device is safe and well tolerated for use both in healthy subjects and patients with glaucoma. Based on pooled data from a variety of studies, the CLS does not appear to have a strong impact on the central corneal thickness (CCT) or corneal hysteresis (a measure for the corneal viscoelasticity). Some of the reported individual studies have observed significant increase, as well as decrease of the CCT after overnight CLS wear that were not considered to be clinically relevant.
The CLS has previously been validated ex vivo in enucleated porcine eyes with good agreement of the CLS output with manometry values. For practical reasons, mostly related to obtaining a good fit of the CLS on the ocular surface, in vivo manometric studies in animal models and patients are more difficult and may be of limited translational value. The signal output of the CLS has been validated in a sleep lab study demonstrating a high accuracy between the CLS 24-hour pattern and the tonometric 24-hour pattern with controlled patient activity. Using the CLS, a published study reported a moderate agreement between 24-hour IOP-related patterns in ambulatory glaucoma patients and suspects, when monitoring was repeated at a one-week interval. These findings are similar to that reported for daytime repeat IOP curves of healthy subjects or patients with glaucoma. Neither study however, controlled for activity of the subject. Furthermore, the CLS output recorded IOP-changing events (e.g. postural change, water drink test), sometimes characterized by a lag time as compared to tonometry as a consequence of the complex non-linear pressure/volume/tissue behavior relationship. Preliminary data indicate that the CLS output is of clinical use in demonstrating the treatment effect before and after laser therapy in patients with glaucoma. This is the a-b-c of this new language.
The next step is to understand this new language of IOP-related patterns further, while building the clinical utility of the device. An analogy is the electrocardiogram language that has ultimately been deciphered, and became an elementary component of managing patients with cardiovascular disease. Data derived from 24-hour IOP-related patterns may distinguish between specific disease states (e.g. slow versus fast progression, stable ocular hypertension versus ocular hypertension converting to glaucoma), and may therefore be a valuable attribute in managing patients with glaucoma, in particular those at risk for progressive disease. 24-hour IOP profiles and relevant patient and treatment data will be centralized in a registry and processed by powerful modeling and learning algorithms to identify pathological patterns that can be used to provide normative patterns, to differentiate indication, to personalize treatment, and to predict risk of progression or of conversion to glaucoma in at risk populations.
Further on the horizon, the interplay of blood pressure (BP), intracranial pressure (ICP) and IOP may open the door to understanding the circadian ocular perfusion pressure and trans-lamina cribrosa pressure, both thought to be implicated in the pathophysiology of glaucoma. Or possibly one might find that volumetric fluctuations are the key metric at the end of the day, IOP having been the best surrogate … so far. Clearly, when it comes to IOP, there is more than meets the eye.
Medgadget: Right now the SENSIMED Triggerfish is already being clinically evaluated. What were the hardest challenges getting your product to this stage? And do you expect to be facing any more challenges before it will become commercially available worldwide?
Dr. Goedkoop: Initially, the lack of calibration to mmHg was a major objection voiced by the medical community. Clinical studies directly comparing tonometry to CLS output between eyes and in transient conditions were confusing, and did recently lead to a deepening of Sensimed’s tenacity to enter relatively unexplored territory of the pressure/volume/tissue behavior relationship in order to understand the observed phenomena. As such calibration remains under investigation, and has driven Sensimed to further understand the pressure/volume/tissue behavior relationship and mathematical signal analysis and modelling.
The interest of the aforementioned objective however has shifted to the notion that the true value is in visualizing and further understanding of the 24-hour IOP-related pattern and its potential to provide information on interventional treatment effect (e.g. compare 24-hour curve before and after intervention) and specific disease state to facilitate the management of patients with progression of their glaucoma.
It is also noted that Sensimed is the leading company in the 24-hour IOP-related pattern recording. There are however both permanent (implantable) and other non-permanent propositions in early development.
Medgadget: Do you already know when the SENSIMED Triggerfish will become commercially available worldwide? And could you tell more about the re-usability and costs of this technology?
Dr. Goedkoop: The device is currently at restricted commercial stage in a number of CE-mark countries, undergoing either various post-marketing clinical studies with centers to explore the potential of the new information provided, or with a selected number of centers for office use in progressing patients. The company expects to broaden-up the availability of the device by 2014. The CLS is single use, and its price will be finalized at that time. Sensimed has submitted its 510K dossier for SENSIMED Triggerfish® to FDA.
Link: Sensimed website…