August 11, 2022 | Contact lenses may have first arrived to help correct vision impairments, but new tech advances are transforming this familiar product into a tool capable of far more.
This summer, for example, American start-up company Mojo Vision announced the on-eye demonstration of its augmented reality smart contact lens (SCL). “Much to my delight, I found I could interact with a compass to find my bearings, view images, and use an on-screen teleprompter to read a surprising but familiar quote,” wrote CEO Drew Perkins.
The development is one among many as an array of research groups and companies continue to make headway in this field. And some of these efforts aim to use SCLs to help evaluate health, diagnose disease, or treat a variety of issues.
Chinese researchers have recently revealed their wireless contact lens capable of detecting changes in eye pressure and delivering anti-glaucoma drugs as needed. Glaucoma damages the eye’s optic nerve, often due to fluid build-up that increases pressure inside the eye, and the disease can lead to irreversible vision loss. For now, tools used to examine the tension of the eyeball tend to provide mere “snapshot” measurements that may miss out on important fluctuations in pressure.
The group of researchers at Sun Yat-Sen University in China sees an opportunity for long-term and continuous monitoring using SCLs that could help regulate this intraocular pressure (IOP).
Their findings, published in Nature Communications (DOI: 10.1038/s41467-022-29860-x), show—in testing with rabbits—that lens-delivered medication led to a significant reduction in IOP within a half hour and helped maintain reduced pressure for a prolonged stretch of time whereas eye drops reduced pressure for a shorter duration before returning to initial levels.
Referred to as a theranostic lens—one that combines therapeutics and diagnostics—they view it as a “highly promising system for glaucoma treatments.”
Why the Eyes are Attractive to Developers
As one of the most complex organs in the human body, the eye is a treasure trove of physiological information, such as IOP and corneal temperature, and tear fluid contains a mixture of biological signals like glucose, proteins, and pH.
Beyond that, some say tears have advantages over other materials commonly used for monitoring biosignals, like ease of access or low complexity of sampling.
Measuring tears is non-invasive and painless compared to blood, and it’s more convenient than measuring markers in urine or sweat, according to Barrett Eubanks, an ophthalmologist and cornea surgeon.
Perhaps the biggest advantage is that tears are so readily available: “there are always tears on the surface of the eye,” he told Diagnostics World. “In addition, measurements in tears can correlate well with measurements within our blood.”
Considering all this potential, efforts have emerged to develop SCLs that could function as a wearable device capable of continuous monitoring and real-time detection of signals stemming from the eyes and tear fluid.
Researchers at the Terasaki Institute for Biomedical Innovation in California have reviewed recent advances, lingering challenges, and future opportunities as developers attempt to harness the potential of SCLs moving forward.
In a paper published in Advanced Materials (DOI: 10.1002/adma.202108389), they explored materials, fabrication, and platform designs; recent advances in SCLs for clinical translation; and options for power transfer and wireless data transmission.
As part of this extensive overview, they also examined diagnostic potential, detailing efforts to use SCLs to monitor IOP, glucose, hormones, enzymes, and cytokines. They also covered applications in ocular electrolyte analysis.
While they acknowledged the wide-ranging and formidable challenges facing the field, the Terasaki Institute researchers remain optimistic considering all the progress made so far and the amount of research taking place across the globe.
Ultimately, they envision ocular biosensors becoming “a powerful diagnostic tool in the near future” and see their review as a resource that can help guide those who are pursuing research and development in this realm of science and technology.
The measurement of fluid pressure inside the eye is useful considering abrupt increases or decreases can indicate a heightened risk of developing certain issues, such as retinal detachment or glaucoma.
IOP can be an important sign of glaucoma, said Yangzhi Zhu, lead author of the Advanced Materials paper and an assistant professor at the Terasaki Institute.
SCLs could be used to monitor IOP fluctuations in real time to indicate if a person has the potential to develop this disease—or to learn whether a drug treatment has worked, he told Diagnostics World.
Sensimed is one company that has made inroads in this space with its CE-marked and FDA-approved device. The system, called Triggerfish, provides insights into ocular volume changes and provides information that can help guide treatment.
The eyes change over the course of a day in response to factors like pressure, volume, stress, and circadian rhythm, according to the company’s website. Triggerfish, which is worn for a full 24-hour timespan, is designed to provide a more comprehensive picture than a typical visit to the doctor’s office.
The sensor comes in the form of a soft contact lens. The adhesive antenna, put around the eye, receives information wirelessly. That data is transmitted, using a cable, from the antenna to a portable recorder worn by the patient. Using Bluetooth technology, the data is transferred from the recorder to a software program.
Because there are several forms of glaucoma treatment, some more invasive than others, the data gathered can be used to help guide the decision-making process.
The finger-prick is a commonly used method for glucose detection, used by diabetic patients to keep tabs on their blood glucose levels. But this method can be inconvenient—and only provides information at singular points in time. In addition, there is pain involved with all those finger pricks, Zhu said.
Some have viewed tear fluid as a viable alternative. Prior publications have confirmed that there is some correlation between the glucose levels in tears and blood glucose, he explained, which offers promise for developing sound techniques that rely on tears instead of blood.
Back in 2014, Google (via Verily) and Novartis (via Alcon) joined forces to pursue SCLs for diabetics—a project eventually shelved several years later.
The association between blood and tear glucose concentration has come into question during attempts to distinguish between diabetic and nondiabetic people using tear glucose levels, Zhu et al acknowledged, and this was “further fueled by the hiatus of the Verily-Alcon SCL program.”
But the inability to make a clear distinction between diabetic and nondiabetic individuals using tear glucose levels does not necessarily equate to a lack of correlation between tear and blood glucose, they pointed out.
In recent years, scientists have continued to pursue ocular alternatives to the finger-prick. In a 2022 review paper (DOI: 10.3389/fmed.2022.858784), researchers at the Istituto Italiano di Tecnologia in Italy and Khalifa University of Science and Engineering in the United Arab Emirates detailed the latest advances.
The authors explained that SCLs for continual glucose detection can be divided into three main categories based upon the type of sensor integrated into the lens: light diffractive, fluorescent, and electrochemical. They discussed each of these categories, along with their unique advantages and drawbacks.
Ultimately, they see the eyes as a sensing site with plenty of potential. “Contact lens sensors represent a viable route for targeting minimally-invasive monitoring of disease onset and progression,” they wrote. “Particularly, glucose concentration in tears may be used as a surrogate to estimate blood glucose levels.”
Hormones, Enzymes, and Cytokine Monitoring
The use of SCL wearable platforms for monitoring other biomarkers (such as hormones, enzymes, and cytokines) is also being explored.
For example, cortisol can be triggered by stress, and chronic stress can lead to the abnormal secretion of this hormone. The accumulation can eventually lead to health problems like diabetes, anxiety disorders, or cardiovascular issues. Checking in on cortisol levels using SCLs may be a way to help fend off these types of problems before they set in.
Other work in this space looks to tackle chronic ocular surface inflammatory (OSI) diseases. A study published last year, for example, reported a human pilot trial of an SCL and skin-attachable therapeutic device for the wireless monitoring and treatment of OSI (DOI: 10.1126/sciadv.abf7194).
As a diagnostic device, the lens enables the real-time measurement of the concentration of a biomarker for OSI called matrix metalloproteinase-9 (MMP-9). The therapeutic device is a heat patch that can attach to the eyelid.
For patients with dry eye syndrome, the pH value of tear fluid may rise higher than the value seen in healthy ocular fluid. Sodium ion concentrations can also be higher for those with this condition.
Dry eye disease is a condition SCLs could help address by measuring pH change or sodium concentration levels, Zhu explained, thereby enabling timely treatment of eye conditions before they worsen.
A group of UK researchers have revealed their progress in this area with a study detailing an SCL that utilizes a microfluidic system embedded with pH, protein, glucose, and nitrite chemical sensors (DOI: 10.1016/j.snb.2020.128183).
With further improvements, they indicated that this proof-of-concept device could be used to help diagnose and monitor diseases like keratoconus, uveitis, rosacea, and diabetes.
Challenges Facing the Field
Despite all the inroads made in recent years, the SCL field still faces challenges regarding fabrication methods, material designs, and commercialization.
Although advances in semiconductor technology are leading to the use of smaller chips and components than ever before, Zhu said that integrating all functional units into such a tiny space remains one of the most notable ongoing difficulties.
Possible side effects of wearing SCLs (such as dry eye) remain a central issue, and so does the selection of appropriate biomarkers. One of the biggest hurdles, furthermore, is ensuring these devices are safe.
Extensive testing is needed before SCLs can be worn by humans. The process of gaining regulatory approval is complex, and the time and expense involved means only a fraction of the projects initiated wind up making the jump from lab to market.
Sensimed’s Triggerfish was highlighted as a prime example of this long, difficult road to market. “This clinical trial had to pass two years of safety and tolerability tests and four years of multicenter sensor efficacy trials,” Zhu et al pointed out.
Yet another hurdle pertains to the issue of reproducibility. As technology moves forward, SCL products could become more and more complicated, and aspects like packaging and shelf life can wind up affecting scalability.
In terms of emerging trends, Zhu said some applications are now utilizing 3D printing for added functionality and others are attempting to integrate AI or machine learning to help improve the accuracy of data flow.
As he envisions the future of the field, Zhu thinks the next generation of SCLs should work to combine diagnostics and therapeutics. A closed loop system that monitors signals and triggers the release of medication could help advance personalized healthcare applications, he added.
Paul Nicolaus is a freelance writer specializing in science, nature, and health. Learn more at www.nicolauswriting.com.