Soft contact lenses, from their inception, were envisioned to have applications beyond the correction of refractive error. This is evident already today, with contact lenses on the market already having indications, such as to slow the progression of myopia or to act as a bandage, that are beyond vision correction. 

In the BCLA CLEAR – Contact Lens Technologies of the Future publication,1 experts from around the globe were tapped to provide a snapshot on the future applications of contact lenses and contact lens technology, the research underpinning this technology and their current status in development. 

The article is neatly divided into nine broad topic areas, indicating the breadth of the fields that contact lenses are being investigated to be used in the future. 

It will article will provide brief overviews of each of these nine areas identified as potential applications for contact lenses in the future, and the reader is encouraged to read the full article for further details.

Potential future applications of contact lenses beyond the correction of sight:

  • Diagnosis and screening for systemic disease
  • Diagnosis and screening of ocular disease
  • Treatment and management of ocular conditions
  • Drug delivery to the ocular surface
  • Antimicrobial contact lenses 
  • Heranostics
  • Optical enhancements
  • Advances in contact lens packaging
  • Future storage cases

1 Contact lenses for the diagnosis and screening of systemic disease

When used, contact lenses are in constant contact with one of the body’s fluids, namely the tear film. Naturally, as interest in investigating the tear film for biomarkers of disease has increased, so has the interest in using a contact lens to serve as a sensor for these markers. For example, potential tear biomarkers for Alzheimer’s disease, cystic fibrosis, multiple sclerosis and thyroid disease have been identified within the literature.1 

There have also been varied types of sensors or indicators built into lens materials, from colorimetric or fluorescent means of detection to electrochemical signal generation, which need to be read with an external reader, including potentially a smartphone.1 One application which has generated significant interest was the use of contact lenses for the detection of glucose levels within the tears as a correlate to blood glucose levels. Numerous research papers have been published detailing the design and detection of glucose in tears using a contact lens platform.1 

However, the underlying physiology of the tear film has proven to be a great challenge, as the tear glucose levels relative to blood levels have been found to experience a time delay.1 Cancer detection with contact lenses has focused on a range of proteins that are known to be upregulated in certain cancers and their presence and levels within the tear film. 

In this application, a contact lens detection platform is envisioned to either detect these markers within the tear film or be used to capture these accumulated markers within the lenses during wear which can be processed after lens removal.1

2 Contact lenses for diagnosis and management of ocular disease

The Sensimed Triggerfish contact lens sensor device is probably the most well-known contact lens sensor, as it has reached commercialisation and approval for use in the EU and the USA. The device is designed around measuring changes in the corneal curvature in response to changes in intraocular pressure detected via a strain gauge. As it does not directly measure intraocular pressure, the device has been marketed as an aid to indicate when the IOP should be best measured during the diurnal variation in pressure so that the maximum pressure experienced by the eye can be captured.

The device measures for 30 seconds every five minutes, leading to 288 measurements over the course of 24 hours. Data is transmitted wirelessly to an antennae receiver, which is mounted on the eyelids and orbit around the eye before being passed to a recorder worn around the neck, allowing for patients to use the device while performing their usual tasks of daily living (figure 1).1 

Figure 1: (a) Appearance of SENSIMED Triggerfish device on the eye, and (b) antennae/receiver placed on the skin surrounding the eye. Reproduced with permission

Future iterations and generations of the device and others are seeking to further miniaturise the data capture and powering of these devices so that they are less intrusive, as well as the contact lens design itself, which in its current form is made quite thick and of a silicone elastomer material, which may have less desirable comfort properties.

Other sensors in development for use with contact lenses have included those for osmolarity of the tears in the management of dry eye, inflammatory cytokines as a measure of inflammation on the ocular surface, and further applications looking at sensing the blink rate, ocular temperature and ocular vasculature responses to lens wear.1

3 Contact lenses for the treatment and management of ocular conditions

Medical uses of contact lenses are varied, and a more detailed overview and discussion of these applications led to one of the other BCLA CLEAR publications, the BCLA CLEAR Medical Uses of Contact Lenses, going further in-depth for this area (This is covered as the eighth in the current series of BCLA CLEAR articles in Optician).2 Here, it is useful to highlight where the medical use of contact lenses has progressed in current contemporary practice as well as what is in the pipeline.

Beyond the use of contact lenses as a healing bandage, one of the more transformative applications has been the use of contact lenses to aid limbal stem cell deficiency, where in small-scale pilot experiments, limbal stem cells could be seeded on to soft lenses, delivered to a damaged ocular surface and restore the critical functioning of epithelial cells, increasing rates of transplantation success compared to other methods.1, 3, 4

The use of technology to manage diseases of the iris is also illustrative of where the technology may go with contact lenses in these applications. Artificial, static irises painted or printed on to contact lenses have been available for many years, and this has been advanced by researchers developing responsive apertures using things such as miniaturised liquid crystal cells to respond to changing light conditions. 

These are envisioned to be applied for patients with iris defects or even transillumination defects to provide a more dynamic response to light. Other applications discussed include lacrimal gland stimulation for dry eye, scavenging of matrix metalloproteinases and reactive oxygen species to remove oxidative stress, and aiding in colour vision deficiency using filters.1

4 Drug delivery to the ocular surface with contact lenses

One of the largest sections of this article detailed the advantages conferred with drug delivery to the ocular surface with the use of contact lenses and the different strategies that have been utilised by researchers in the field to control and tailor drug release. An often repeated anecdote is that the potential for soft contact lenses to deliver drugs was included in the original patent for these devices; the challenge, however, has been successfully identifying a set of suitable drugs and diseases to be treated by contact lens drug delivery.

The advantages discussed in the paper for contact lens delivery included increasing the bioavailability of drugs compared to eye drops, where only 5% of the active ingredient may be able to be absorbed effectively to reach its target site of action. The use of contact lenses is also a potential avenue for more consistent or accurate dosing of drugs so long as there is consistency in the lens-to-lens variation of the amount of drug loaded and delivered.

In contrast, eye drops have the potential for significant variability due to the need for patients to utilise the drops correctly, where the amount that bottles are squeezed, the aim of the bottle and drop, and the angle administered all being factors leading to drop dosage variability. The use of a contact lens drug delivery system may also aid in patient compliance as well as remove the need for preservatives, as the lenses themselves are typically sterilised at the end of the manufacturing process.

There are, however, several challenges to contact lens drug delivery. Fundamentally the success of such a combination will depend on the appropriate selection of a contact lens material and a drug, as well as a condition to be treated, as different materials may take up different amounts of different drugs and deliver them at different rates. 

The drug itself would also need to be able to go through numerous steps of contact lens manufacturing and processing, some of which may require high temperatures or light exposure. Lenses also may have different properties, such as thickness differences, depending on the lens design, such as the refractive power being conferred on to the wearer.

Notwithstanding all of these impacts is the fact that the device will need to continue to behave as a contact lens, and thus would need to still correct for refractive error, be optically transparent and compatible with the ocular surface. The regulatory hurdles would also need to be considered, and approval processes may potentially be complicated by the disease being treated and the ability of the system to demonstrate effectiveness, the envisioned wear and replacement schedule of the lenses and the safety of the combination.

One of the main focuses of the field of contact lens drug delivery has been on the manipulation or tailoring of drug release from these devices while also ensuring a sufficient amount of the drug is able to be loaded on to them. This has included the encapsulation of drugs into carriers, including nanoparticles, cyclodextrins and PLGA films, or increasing their solubility using microemulsions and then having these placed on to the surface of the contact lens or into the material itself. The use of these carriers allows for a potentially greater amount of the drug to be loaded into the lenses, which can then be slowly released.

Other methods have looked into modifying the material the lenses are made of themselves, including using techniques such as molecular imprinting, which create, on a polymer level, specific areas of greater affinity for a drug of interest; manipulation of the ionicity of the lenses through additives to increase ionic interactions with charged drugs; and the use of coatings or barriers, with Vitamin E having been studied extensively to serve as a biocompatible, clear barrier that slows the passage of drugs from loaded contact lenses.

The drugs selected for investigation for delivery from contact lenses have spanned from antimicrobials, anti-inflammatory, immunomodulators, anti-glaucoma and anti-allergy agents, and testing have included laboratory studies examining the release kinetics into static or replenished solutions, as well as in pharmacokinetic studies in animals and animal disease models. 

A commercially available contact lens drug delivery device, based on the etafilcon A material, was recently released onto the market in Canada and Japan and has received FDA approval.5 The device releases the anti-allergy drug ketotifen fumarate for the management of ocular allergy and is fit as a daily disposable. Its release to the market shows the commercialisation potential and interest in drug delivery from contact lenses.5

Current and future applications of contact lenses in drug delivery:

  • A ketotifen fumarate releasing anti-allergy contact lens has reached the commercial marketplace
  •  A tailored dosage of a variety of drugs such as antimicrobials, anti-inflammatory, immunomodulators and anti-glaucoma
  • Increased bio-availability of the drugs at the ocular surface when delivered using a contact lens

5 Antimicrobial contact lenses

With ongoing goals of improving the safety of contact lenses from infection or inflammation associated with microbiological contamination, the incorporation of antimicrobial peptides on to contact lens surfaces has been published extensively in the literature. Melamine, a synthetic antimicrobial peptide derived from salmon sperm and bee venom, and its modified smaller derivative, Mel4, have been reported in the literature for their impact on infection or contact lens complications after incorporation on to the surface of lenses.6, 7

Not only have these been utilised and tested for their biocompatibility and antimicrobial activity in the laboratory, but in phase II and III clinical trials demonstrating that the use of such a lens can lead to a lower microbial bioburden on the lens and lower incidences of infiltrative events.1 

Esculentin-1a is another antimicrobial peptide that has been attached to the surface of contact lenses, while not impacting critical contact lens parameters but also slowing or preventing bacterial adhesion. See figure 2.

Figure 2: Contact Lens-Induced Acute Red Eye (CLARE) seen with control lens wear could be reduced with antimicrobial Mel4 coated lenses.6 White arrows indicate the infiltration in the limbal (A and B) and mid-peripheral cornea (c) (Image courtesy Dr Debarun Dutta, Aston University)

6 Theranostics

Given the potential for contact lenses to both detect and treat disease, a theranostic application of contact lenses also has been proposed. Theranostics, a portmanteau of therapeutics and diagnostics, is a branch of research investigating devices that can both detect a disease state as well as exert a therapeutic effect in response to it. 

Here, glaucoma management in response to a change in IOP has had the greatest interest due to the commercial availability of the Triggerfish device as well as the work that has been performed on drug delivery.

A recent article has detailed the design, manufacturing and  evaluation of a combination IOP sensing and glaucoma drug-eluting lens.8 The device was wirelessly powered and utilised a unique cantilevered capacitor design to detect small changes in IOP, and wirelessly trigger the release of the anti-glaucoma drug brimonidine.8 

Another area that has seen interest has been dry eye, with the hope that the increase in certain enzymes in the disease, particularly MMP-9, can lead to selective degradation/release of therapeutic agents from the lens’ surface, placing MMP-9 levels at the centre of the severity of the dry eye disease state.

7 Optical enhancements

The potential optical enhancement applications of contact lenses span from attempting to manage or decrease optical aberrations enhancement for sport or low vision and augmented vision.1

Some of the more interesting developments in accommodative contact lenses is detailed in the patent literature, where there are descriptions on how lenses can be designed to detect gaze position, signal that gaze to a controller, which then uses a controller and external power supply to determine the required focus. 

This is then relayed to a changeable optical system integrated on the lens, with most suggestions being some sort of electroactive element, such as liquid crystals, which can form rods whose orientation can be controlled by the presence or absence of an electric current, changing the refractive index.1

A relatively newer development in this area is virtual and augmented reality smart contact lens prototypes that are functional with a micro LED display and medical grade micro batteries.9 These lenses allow wearers to see images in 3D similar to virtual reality or augmented reality, where information is overlaid on the person’s real environment. The lens has a microdisplay with 14,000 pixels per inch in a diameter of only 0.5mm.9 The self-contained futuristic lens could have widespread use in commercial sector including for daily life.

Enhancement for low vision with contact lenses has centred on having the lenses serve as one part of a Galilean telescope, with the neutralising lens of the system being found on the spectacle plane.1 

Enhancement for sports has mainly focused on the use of tints, while augmented vision discussed within the literature has ranged from edge or distance enhancement to entire overlays placed into the visual space to provide real-time information of various interests.1

8 Contact lens packaging

Developments in contact lens packaging within the industry have primarily focused on reducing the contamination of lenses when removed and placed on to the eye during lens application. The most prominent example of this technology reaching the market has been the introduction of Smart Touch Technology, (figure 3), where the blister is deliberately designed so that the outer surface of the lens is presented to the user when the packaging is opened. 

If properly handled and applied from this presentation, the argument is that the inner surface of the lens that is in contact with the eye can remain as contamination free as possible.1

Figure 3: Smart Touch packaging in two blister designs to avoid the need to touch the inner contact lens surface during removal from the blister. Reproduced with permission

9 Future storage cases

Similar to contact lens packaging, the focus of developments for storage cases is on reducing microbial contamination or indicating in some way that a case has reached unacceptable levels of contamination while in use.1 Reduction in contamination in storage cases has primarily utilised silver or selenium incorporated into the lens cases, which in vitro demonstrate a significant reduction in the number of bacteria recovered, although this is reported to only occur after 24 hours of incubation, with less activity detected if used for only six or 10 hours.1 

Use of the cases clinically, unfortunately, did not demonstrate a significant impact on case contamination, with more than 70% of cases incorporating silver being contaminated after one month, and with no significant impact on reducing adverse events.1 To detect contamination, researchers have described within the literature the use of gold nanoparticles, tetrazolium dye or potentially a peptide-graphene nanosensor as indicators of unacceptable levels of bacteria or other microbes within lens cases.1 See figure 4.

Figure 4: Example of biosensor incorporated into a contact lens case. The blue indicates bacterial contamination using tetrazolium dye. Reproduced with permission

Conclusions

Clearly, there have been numerous other developments in the world of contact lenses for applications beyond the simple correction of refractive error. From medical applications such as the detection or treatment of a disease to enhancing the visual world for everyday use or for special cases such as sports or low vision, there are examples within the literature of groups who are working in these areas that provide a glimpse into what contact lenses will be used for in the future. With the recent commercial release of contact lenses to slow the progression of myopia and for anti-allergy drug delivery, the future applications of contact lenses in many ways are already here and it will be fascinating to see what will become available in the next few years. 

The editors of this series are Neil Retallic and Dr Debarun Dutta.

Acknowledgements

Acknowledgements to the co-authors of the original CLEAR - Contact Lens Technologies of the Future publication, including Lyndon Jones, Chau-Minh Phan, Michael Read, Dimitri Azar, John Buch, Joseph Ciolino, Shehzad Naroo, Brian Pall, Kathleen Romond, Padmaja Sankaridurg, Christina Schnider, Louise Terry and Mark Willcox.

Original paper: Jones L, Hui A, Phan C-M, Read ML, Azar D, Buch J, Ciolino JB, Naroo SA, Pall B, Romond K, Sankaridurg P, Schnider CM, Terry L, Willcox M. CLEAR - Contact lens technologies of the future. Contact Lens and Anterior Eye 2021;44:398-430.

References

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  2. Jacobs DS, Carrasquillo KG, Cottrell PD, Fernández-Velázquez FJ, Gil-Cazorla R, Jalbert I, et al. CLEAR – Medical use of contact lenses. Contact Lens and Anterior Eye 2021;44(2):289-329. https://doi.org/10.1016/j.clae.2021.02.002.
  3. Di Girolamo N, Bosch M, Zamora K, Coroneo MT, Wakefield D, Watson SL. A contact lens-based technique for expansion and transplantation of autologous epithelial progenitors for ocular surface reconstruction. Transplantation 2009;87(10):1571-8. https://doi.org/10.1097/TP.0b013e3181a4bbf2.
  4. Di Girolamo N, Chui J, Wakefield D, Coroneo MT. Cultured human ocular surface epithelium on therapeutic contact lenses. Br J Ophthalmol 2007;91(4):459-64. https://doi.org/10.1136/bjo.2006.103895.
  5. Pall B, Gomes P, Yi F, Torkildsen G. Management of Ocular Allergy Itch With an Antihistamine-Releasing Contact Lens. Cornea 2019;38(6):713-7. https://doi.org/10.1097/ico.0000000000001911.
  6. Dutta D, Vijay AK, Kumar N, Willcox MDP. Melimine-coated antimicrobial contact lenses reduce microbial keratitis in an animal model. Invest Ophthalmol Vis Sci 2016;57(13):5616-24. https://doi.org/10.1167/iovs.16-19882.
  7. Dutta D, Kamphuis B, Ozcelik B, Thissen H, Pinarbasi R, Kumar N, et al. Development of silicone hydrogel antimicrobial contact lenses with mel4 peptide coating. Optom Vis Sci 2018;95(10):937-46. https://doi.org/10.1097/OPX.0000000000001282.
  8. Yang C, Wu Q, Liu J, Mo J, Li X, Yang C, et al. Intelligent wireless theranostic contact lens for electrical sensing and regulation of intraocular pressure. Nature Communications 2022;13(1):2556. https://doi.org/10.1038/s41467-022-29860-x.
  9. Whitwam R. Mojo Vision Details Its First Smart Contact Lens; 2022. Available from: https://www.extremetech.com/extreme/337691-mojo-vision-details-its-first-smart-contact-lens. [Accessed 20 May 2023].