Biosensors in contact lenses can monitor IOP and diabetes


Work is progressing on contact lenses that can monitor biomarkers in tear film for intraocular pressure, diabetes mellitus, and other health conditions.

Work is progressing on contact lenses that can monitor biomarkers in tear film for intraocular pressure (IOP), diabetes mellitus, and other health conditions.

“Assuming that the technology performs as intended, the widespread use of contact lens sensors could provide a paradigm shift in clinical management of a variety of diseases,” wrote Chau-Minh Phan and colleagues of the Centre for Contact Lens Research, School of Optometery and Vision Science, Waterloo, Canada in Optometry and Vision Science.

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Although the investment of Alphabet (the parent company of Google) in the technology has attracted headlines, multiple other companies are working on competing versions. Yet none has completely overcome the significant technical and clinical barriers to widespread use.

Because IOP can fluctuate during the course of a day, the gold standard for its measurement, Goldmann applanation tonometry, gives an incomplete picture. Measurement position can also influence results.

In 2009, Sensimed (Lausanne, Switzerland) launched the Triggerfish IOP-monitoring contact lens to address this challenge, the authors wrote. The device won approval from Conformité Européene in 2010 for commercialisation in Europe, but so far has not attained approval from the US Food and Drug Administration.

It uses four circular strain gauges capable of sensing circumferential changes at the limbus, Phan and colleagues reported. Relative variations in IOP show up as a result of changes in ocular volume, they said.

An embedded microprocessor and antenna in the contact lens sensor transfer the data wirelessly to an external eyepiece, and the data are stored on a portable unit worn on the waist or neck.

In clinical trials, the results proved highly reproducible, and because no force is needed on the cornea, they are independent of the investigator and patient, the authors said.

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However, validation between the contact lens sensor and tonometry has proved difficult because of the impossibility of simultaneous measurement using the contact lens sensor and tonometry on the same eye.

In addition, the eyepiece as currently designed is “both crude in appearance and large,” wrote Phan and colleagues. And the contact lens is larger with a higher modulus than a typical soft contact lens, making it relatively uncomfortable.

However, the Triggerfish might prove useful for use over the course of 24 hours to glean information about fluctuation in IOP, with this information coupled to conventional measurements, they reported.

Monitoring for diabetes


Diabetes stands out among the conditions that might lend themselves to longer term monitoring.

Most often patients monitor their diabetes with enzyme-based finger pricks, which are painful and inconvenient and could lead to infections.

One alternative approach is based on boronic acids, which bind to diol-containing species such as carbohydrates. One such approach uses boronic acid fluorophores (BAFs), which induce spectral changes in the presence of sugars through an excited state charge transfer mechanism. So far, though, the BAF response has not been sufficiently sensitive after incorporation in a contact lens.

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Another fluorescence approach uses concanavalin A in a competitive assay. An attempt by Eyesense (Grossotheim, Germany) to commercialise this approach proved unsuccessful, the research reported.

Other researchers have used enzyme-electrode-based mechanisms that take advantage of oxidation of glucose by glucose oxidase into hydrogen peroxide. Further oxidation of the hydrogen peroxide at the electrode releases free electrons, producing an electric current that can be coupled with a transmission system to produce a wireless sensing device, the authors wrote.

Building on the research of others, Verily, a division of Alphabet, has developed this technology in partnership with Novartis. The system includes an antenna, a wireless sensor interface chip and a glucose sensor polymer substrate for the detection of tear glucose.

This approach has shown high sensitivity and selectivity. But the enzyme has a short lifetime, and enzymatic sensors can also be affected by the typical sterilisation methods used in the contact lens industry, such as autoclaving, wrote Phan and colleagues.

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The immobilisation of the enzyme on the substrate has posed a barrier to this approach and so has enzymatically generated water, which is susceptible to interference with redox-active molecules such as ascorbic acid, said the authors. For this reason, research is now focusing on novel nanostructures with glucose-sensing properties, but this technology remains in the early stages.

Clinical difficulties have also imposed barriers to the development of a glucose-sensing contact lenses, said Phan and colleagues. To be effective the sensor must constantly monitor glucose levels and warn patients who are in danger of hyperglycemia so that they can inject themselves with insulin.

But patients who depend on insulin injection also risk developing severe hypoglycaemia, which also need to be monitored in a timely manner, especially at night when blood glucose often drops. Yet blood glucose takes an average of 20 minutes to appear in tear fluid, and then the glucose must diffuse through the contact lens to reach the biosensor, the authors reported. This lag time could make this method of glucose monitoring insufficient for patients at high risk from hyperglycaemia or hypoglycaemia.

Future obstacles


Continuous contact lens wear can also be uncomfortable, and increase the risk of microbial keratitis, contact lens peripheral ulcers, and inflammatory complications. In elderly patients, who are most often in need of this type of monitoring, the problems of intolerance and disabilities preventing contact lens insertion and removal are particularly common, Phan and colleagues noted.

For some conditions, however, the wearer could remove the contact lens soon after insertion allowing analysis and quantification of biomarkers outside the eye. This approach could lend itself to conditions such as dry eye and cancer that don’t require continuous monitoring.

At the same time, contact lens sensor technology faces some other significant obstacles. Tear analysis can be difficult because of variations in the tear proteome, the low concentration of biomarkers in tear film, and variations with sex, age, and time of day.

Still, the authors noted, if these barriers can be overcome, contact lens sensors could produce immense amounts of information, leading to better effective treatments and improvements in individualised medicine.

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