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Corresponding author at: Centre for Ocular Research & Education (CORE), School of Optometry & Vision Science, University of Waterloo, Waterloo, Canada.
Centre for Ocular Research & Education (CORE), School of Optometry & Vision Science, University of Waterloo, Waterloo, CanadaCentre for Eye and Vision Research (CEVR), 17W Hong Kong Science Park, Hong Kong
Centre for Ocular Research & Education (CORE), School of Optometry & Vision Science, University of Waterloo, Waterloo, CanadaCentre for Eye and Vision Research (CEVR), 17W Hong Kong Science Park, Hong Kong
Department of Ophthalmology and Visual Sciences, University of Illinois College of Medicine, Chicago, IL, USAVerily Life Sciences, San Francisco, CA, USA
Contact lenses in the future will likely have functions other than correction of refractive error. Lenses designed to control the development of myopia are already commercially available. Contact lenses as drug delivery devices and powered through advancements in nanotechnology will open up further opportunities for unique uses of contact lenses.
This review examines the use, or potential use, of contact lenses aside from their role to correct refractive error. Contact lenses can be used to detect systemic and ocular surface diseases, treat and manage various ocular conditions and as devices that can correct presbyopia, control the development of myopia or be used for augmented vision. There is also discussion of new developments in contact lens packaging and storage cases.
The use of contact lenses as devices to detect systemic disease has mostly focussed on detecting changes to glucose levels in tears for monitoring diabetic control. Glucose can be detected using changes in colour, fluorescence or generation of electric signals by embedded sensors such as boronic acid, concanavalin A or glucose oxidase. Contact lenses that have gained regulatory approval can measure changes in intraocular pressure to monitor glaucoma by measuring small changes in corneal shape. Challenges include integrating sensors into contact lenses and detecting the signals generated. Various techniques are used to optimise uptake and release of the drugs to the ocular surface to treat diseases such as dry eye, glaucoma, infection and allergy. Contact lenses that either mechanically or electronically change their shape are being investigated for the management of presbyopia. Contact lenses that slow the development of myopia are based upon incorporating concentric rings of plus power, peripheral optical zone(s) with add power or non-monotonic variations in power. Various forms of these lenses have shown a reduction in myopia in clinical trials and are available in various markets.
Tear Film and Ocular Surface Society Dry eye workshop II
TNF
tumor necrosis factor
1. Introduction
Contact lenses were invented to correct refractive error and they have become a successful, convenient and widely used commodity for this purpose. However, looking forward into the not-so-distant future, the potential applications for these devices are proliferating to uses where vision correction per se is often not the main intention. Industries as far ranging as bio-sensors, pharmaceuticals, defence and the entertainment sector could all potentially apply contact lens-based technologies to achieve solutions to problems for their specific unmet needs. This review will explore some of these innovations and consider how these efforts will change the way contact lenses are used in the future.
2. Diagnosis and screening for systemic disease
Historically, the quantification of analytes in the tear film has primarily focused on the diagnosing and monitoring of ocular conditions. However, it is increasingly apparent that the tear film contains a wide range of biomarkers that may help diagnose systemic disease for a range of conditions [
]. A contact lens-based diagnostic device would allow a biosensor to be placed in close proximity to the ocular tissue and be bathed in the tear fluid, which is known to reflect pathophysiological changes in several systemic and ocular diseases, as described in Table 1.
Table 1Systemic disease biomarkers found within the tear film.
Disease
Potential tear biomarkers
Alzheimer’s disease
Increased levels of dermcidin, lacritin, lipocalin-1 and lysozyme-C [
Biochemical tear film sensing technology is rapidly evolving, allowing the incorporation of either electrochemical or optical sensing technologies into future diagnostic contact lenses [
]. This approach offers distinct advantages over direct tear sampling, as a contact lens enables the cumulative detection of biomarkers during the wearing period, potentially increasing assay sensitivity [
]. In addition, a range of sensing technologies is now available which could be incorporated into future diagnostic contact lenses to monitor clinical ophthalmic biomarkers, including blink tracking [
]. In addition, due to the relatively large surface area of the contact lens, there is potential for multiplexing to monitor various biomarkers at the same time via a single device [
]. Future research will likely focus on identifying and refining the key biomarkers for these conditions, establishing the specificity and sensitivity of the biomarkers for the particular diseases, and developing tear film capturing and sensing technologies to allow such analysis to be truly diagnostic. This will allow the potential for simple contact lens-based technologies that could diagnose systemic disease at an earlier stage, allowing prompt management and improved clinical outcomes.
Two specific examples of research in this area relate to diabetes monitoring via tear film glucose detection and detection of cancer-markers within the tear film.
2.1 Diabetes monitoring via tear-film glucose detection
Diabetes, a chronic condition characterised by high levels of blood sugar, affects more than 463 million people worldwide and is on the rise [
Global and regional diabetes prevalence estimates for 2019 and projections for 2030 and 2045: results from the international diabetes federation diabetes atlas, 9(th) edition.
]. As there is currently no cure, effective monitoring and control of blood glucose levels are critical in managing the condition and its complications. The gold standard for blood glucose monitoring is the finger-prick method, where a lancet is used to pierce the skin of a finger or another site to obtain a blood sample that is read by a glucose meter. This procedure can cause discomfort and is inconvenient, while also raising the risk of loss of sensation and secondary infection in repeatedly sampled areas [
]. Non-invasive methods for glucose detection have thus been proposed to alleviate these complications and improve patient quality of life.
The tear fluid is a potential site for non-invasive glucose monitoring due to its relative accessibility. The concentration of tear glucose is higher in diabetics than healthy individuals [
]. This concept would open up the possibility of continuous tear glucose monitoring rather than the “snapshots” which are provided by monitoring through finger prick testing.
2.1.1 Mode of detection
Glucose detection using a biosensor can be broadly categorised into either optical or electrochemical methods (see Table 2 for examples).
Table 2Examples of glucose biosensors developed for contact lenses.
J. Zhang, W.G. Hodge. Contact lens integrated with a biosensor for the detection of glucose and other components in tears. Google Patents. US8385998B2. USA; 2009.
For optical detection, the binding of glucose to the sensors typically results in a colourimetric or fluorescence change which is measured using an external reader such as a photodetector or a smartphone. Optical sensors are relatively inexpensive and simple to fabricate since they do not require any additional embedded circuits for power or communication. However, optical detection can be somewhat subjective and prone to errors influenced by elements such as lighting conditions and detector distance.
2.1.1.2 Electrochemical detection methods
Electrochemical sensors are more complex, requiring additional micro-components such as a power source, microprocessor and an antenna for external communication. The underlying mechanism of glucose detection in these systems is a redox reaction of glucose by a catalyst into hydrogen peroxide, which is then oxidised at an electrode to release free electrons [
The advantages of the electrochemical approach is that these systems are highly accurate and can provide continuous and seamless real-time monitoring of tear glucose. The challenge of such a system lies in methods harnessing the electric current, translating it into a quantifiable signal and creating the accessory micro-components to an electrochemical sensor. Previous work has discussed the development of a contact lens platform that coupled the current from the glucose sensor with an antenna and microprocessor [
]. This system was powered entirely wirelessly using radio frequencies, solving the difficulties involved with powering the individual micro-components [
]. This concept spurred several startup companies that have tried to develop a so-called “smart” glucose contact lens, the most prominent example being led by the tech giant Google (Mountain View, CA, USA) in 2014, followed later by a collaboration between Google and Novartis (Basel, Switzerland) [
Several forms of glucose-sensors exist in the contact lens-based glucose sensors proposed (see Table 2 for examples).
2.1.2.1 Boronic acid-based glucose sensors
Boronic acids reversibly bind to carbohydrates, particularly diol-containing molecules such as glucose. These acids have unique optical properties when bound to glucose, resulting in a colourimetric or fluorescence change, depending on the specific boronic acid derivative used [
Concanavalin A (ConA) is a lectin or carbohydrate binding protein. A ConA competitive binding assay biosensor has been applied to a contact lens system [
]. In the presence of glucose, the ligand is displaced and glucose instead binds to ConA, resulting in an increase in fluorescence related to the amount of glucose present, with the change in fluorescence measured using a handheld fluorometer [
]. In the presence of water and oxygen, the enzyme converts glucose to gluconic acid and hydrogen peroxide. The hydrogen peroxide is then oxidised at the anode of an electrochemical probe to produce a current corresponding to the amount of glucose in solution [
The significant advantage of enzymatic sensors lies in their specificity for the molecule in question, but a challenge lies in the integration of the microelectronic components into a contact lens platform. Other drawbacks relate to stability, especially for long term storage [
]. However, these sensors are less specific and sensitive to glucose than enzymes such as glucose oxidase.
2.1.3 Challenges to contact lens-based glucose sensors
Aside from the technical challenges associated with integrating a glucose sensor (whether optical or electrochemical) into a contact lens, other issues also challenge the viability of these devices. There is approximately 20 min lag time between changes in blood glucose and tear glucose levels [
]. For patients with insulin-dependent diabetes that require real-time information to accurately calculate and administer insulin to avoid hyper- and hypo-glycemia, the discordance between tear and blood glucose levels [
] may be fatal. Thus, for severe diabetics, a contact lens-based glucose sensor which only measures levels of glucose in the tears may not be relied upon as the only glucose monitoring device. There will also be market challenges related to the adoption of these smart contact lenses, due to their cost and practicality, in addition to regulatory hurdles to obtain approval for the use of such diagnostic devices. The initial hype towards the commercialisation of a contact lens-based glucose sensor has waned since Google and Novartis put aside their joint venture in 2018, citing a variety of technical challenges [
]. Lacryglobin is present in the tear film of patients with colon, lung, breast and prostate cancer, as well as patients with a family history of cancer [
]. Lebrecht and colleagues used time-of-flight mass spectroscopy to compare the tear film of cancer patients and healthy controls, identifying differences in 20 tear film biomarkers [
Contact lens technology may play a key role in offering a platform for sensing these cancer biomarkers, either via a direct measurement using an electronically-active biosensor mounted on a contact lens [
] or by the natural accumulation of tear components within a contact lens material during wear, which could then be analysed following contact lens removal. Such contact lens-based technology would allow early diagnosis, improved monitoring and gauge susceptibility to a range of cancers, aiding the clinician in providing improved patient care.
3. Diagnosis and screening for ocular disease
3.1 Intraocular pressure monitoring for glaucoma
Glaucoma is a leading cause of blindness globally and thus developments in improving intraocular pressure (IOP) monitoring are of great interest to clinicians. However, methods of measuring IOP in clinical practice are suboptimal and do not reflect its dynamic nature, including its circadian variation and short-term fluctuations [
]. Current gold standard tonometry techniques provide an estimate of the IOP only over a matter of seconds, are generally only available during typical clinic hours and take the reading in an upright, seated position. However, studies have suggested that large IOP fluctuations, in particular nocturnal pressure spikes not captured with conventional tonometry, could have a direct impact on glaucoma progression [
]. The use of continuous monitoring over a 24 -h period would therefore provide a more holistic description of the patient’s IOP profile and contact lens sensors have been suggested as a suitable vehicle for this purpose [
The Triggerfish contact lens sensor (Sensimed, Switzerland) (Fig. 1) is a commercially available contact lens device that permits extended monitoring of IOP. This flexible silicone-based contact lens was first described in 2004 [
] and has received both CE marking and FDA approval for 24 -h measurement of IOP. Rather than measuring IOP directly, the device measures minute dimensional changes in corneal shape, which correspond to changes in ocular biomechanical properties and volume, as well as IOP [
Continuous 24-hour monitoring of intraocular pressure patterns with a contact lens sensor: safety, tolerability, and reproducibility in patients with glaucoma.
]. This is based on the principle that a change in IOP of 1 mmHg elicits a change in corneal curvature of 3 μm, for an average corneal radius of 7.8 mm [
Continuous 24-hour monitoring of intraocular pressure patterns with a contact lens sensor: safety, tolerability, and reproducibility in patients with glaucoma.
Fig. 1(a) Contact lens sensor (SENSIMED Triggerfish) on the eye; (b) The sensor transmits the information gathered when in situ to an antenna, which is connected to a portable recorder. (Sensimed AG).
The Triggerfish device has an embedded circumferential sensor consisting of two strain gauges that measure dimensional change. The gauges sit in a circular arc of 11.5 mm diameter, which is the typical position of the corneo-scleral junction, where maximal corneal deformation due to IOP change is assumed to occur [
Continuous 24-hour monitoring of intraocular pressure patterns with a contact lens sensor: safety, tolerability, and reproducibility in patients with glaucoma.
]. The readings are transmitted wirelessly to an adhesive antenna patch placed around the eye and then through a wired connection to the portable receiver worn by the patient. Since the device is wearable, the patient can perform their daily activities as normal with minimal interruption, although device instructions suggest avoiding driving and contact with water. The device is available in three base curves to aid in achieving an appropriate fit and has an oxygen transmissibility (Dk/t) of 119 units to facilitate overnight wear.
Many clinical studies have demonstrated that the Triggerfish device has good safety and tolerability in both healthy and glaucomatous eyes [
Continuous 24-hour monitoring of intraocular pressure patterns with a contact lens sensor: safety, tolerability, and reproducibility in patients with glaucoma.
]. The most common adverse effects seen in clinical trials include transient blurred vision, conjunctival hyperaemia and superficial punctate keratitis. These mild effects are common, being present in up to 95 % of wearers [
Continuous 24-hour monitoring of intraocular pressure patterns with a contact lens sensor: safety, tolerability, and reproducibility in patients with glaucoma.
], but typically resolve within 24−48 hours. A reduction in best corrected visual acuity during and after wear has been noted, possibly due to orthokeratologic effects of intentionally tight-fitting lenses (to minimise lens mobility) [
]. The device outputs measurement in ‘mV equivalent’ units, which are relative to its initial baseline measurement. These outputs are not comparable to tonometric measurements in mmHg, making direct evaluation of accuracy difficult [
] and further work is warranted to explore the accuracy of the device and its relationship with conventional IOP measurement. Continuous IOP monitoring has enabled further investigation of several factors beyond what is possible with conventional measurement techniques, including the effects of topical medication and surgical interventions, certain activities and body position (e.g. supine versus seated), and circadian rhythm [
The Triggerfish is likely to be the first in a generation of commercially available contact lens-based devices to monitor ocular biomarkers of disease. However, there are a number of limitations with the current device, principally driven by the bulky microprocessor and strain gauge assembly, which when encapsulated within the contact lens results in a 325 μm centre thickness, which is 2–3 times thicker than a typical contact lens. Consequently, to ensure sufficient oxygen is able to pass through the lens, particularly during overnight wear, the lens is manufactured from a highly oxygen permeable silicone elastomer material. This combination of a thick lens and relatively stiff material may potentially negatively impact the sensitivity of the strain gauge system and comfort during wear [
]. The need for an external adhesive patch to power and monitor the system would also ideally be addressed in a less obtrusive manner, either by integration into a spectacle frame or by on-lens power systems.
These limitations have led to a range of different technologies being studied in order to develop future systems that are less invasive and more effective at monitoring IOP. A metal strain gauge electrode with an integrated Wheatstone bridge circuit has been developed allowing a thinner lens design and improved sensitivity, although it lacks integration of the control electronics or aerial and evaluation was limited to laboratory testing only [
]. The use of a flexible, highly piezoresistive organic bilayer film sensor has been proposed, which was reported to improve sensitivity to the subtle changes in ocular surface curvature (3–10 times greater sensitivity in comparison with metal strain gauges) [
]. The prototype film sensor was mounted on a rigid contact lens annulus with a wired connection to the external monitoring equipment. Evaluation in a laboratory and clinical setting (single participant) highlighted the ability of the system to monitor change in IOP. The incorporation of a graphene woven fabric into a contact lens has been described [
], demonstrating excellent sensitivity to ocular surface deformation due to large changes in resistivity in the stretchable fabric when IOP changes altered corneal curvature. The graphene woven fabric material was also reported to have reasonable transparency and biocompatibility, although evaluation was limited to laboratory testing with tethered resistance measurements.
An alternative to monitoring IOP with resistive strain sensors is the use of capacitive sensors, which are generally thought to have a higher sensitivity and lower power consumption [
]. These sensors monitor subtle changes in corneal curvature by measuring the resulting change in capacitance due to altered capacitive gap spacing. When combined with an inductor, this change in capacitance influences its resonant frequency allowing this passive device to be read wirelessly [
]. Recently, a passive doughnut-shaped IOP sensor has been developed which consists of a microfabricated capacitor and variable inductor (in the form of a stretchable serpentine wire) that serves as both the sensor and antenna [
]. Near field electromagnetic coupling is used to wirelessly monitor the resonant frequency of the sensor, enabling continuous monitoring of change in corneal curvature induced by IOP variation. This relatively simple passive device avoids the need for lens-mounted electronic chips, with laboratory testing suggesting good sensitivity, although the authors are yet to report on any clinical evaluation.
With many of these IOP monitoring systems, an obvious limitation is that the sensor measures changes in corneal curvature as a proxy for IOP. This means that the measurements are dependent on the biomechanical properties of the human eye and their output is not a direct measure of pressure. In an attempt to address this, a novel IOP sensing contact lens has been developed which operates on the basis of applanation rather than topographical change [
]. This silicone hydrogel lens contains a capacitive pressure sensor mounted into an annular recess in the mid-periphery of the lens. This annular recess causes the underlying portion of the lens to protrude and experience a reactive deformation when pressed into the cornea by the blinking action of the lids or during sleep. The deformation is detected by the capacitive sensor and wirelessly monitored by a portable external controller. This system is claimed to provide profiles of IOP change in actual pressure values (mmHg) and is reportedly less influenced by the mechanical behaviour of the cornea and the sclera [
]. The system has undergone pilot clinical testing, with the device reported to be able to track IOP changes whilst causing only low levels of discomfort [
Due to the complexity of integrating electronics within a contact lens, microfluidic and optical technologies have also been considered. Microfluidic contact lenses typically contain a network of enclosed microchannels, with a fluid level indicator that tracks changes in internal volume due to variations in corneal curvature or IOP. It is envisaged that these microfluidic IOP sensors could be read directly by the clinician or imaged using a mobile phone camera [
]. An alternative approach is based on the generation of optical nanostructures using laser processing on a commercial contact lens, which forms a holographic optical sensor [
]. Although these optical and microfluidic sensors lack the ability to track IOP during sleep or on a continuous basis, their relative simplicity may allow for more rapid sensor development and a lower cost device than electronically active systems [
Rapid progress is being made in developing a broad range of biosensing technologies to support the development of biocompatible minimally invasive contact lens for IOP monitoring. However, with the exception of the Sensimed Triggerfish lens, many of the proposed sensors have had limited, if any, clinical evaluation. This likely relates to (i) the complexity of integrating electronics within a contact lens, (ii) the early stage of development of many of these new sensors and (iii) the costs associated with medical device development and clinical evaluation. However, the latest IOP sensor technology from Sensimed AG (known as “Goldfish” (Clinicaltrials.gov number: NCT03689088)), highlights continuous monitoring of IOP in humans over a 24 -h period [
] using a micro-electro-mechanical system pressure sensor technology, offering an exciting glimpse into the potential impact contact lens-based technology could have on the future of glaucoma diagnosis and management.
3.2 Dry eye disease diagnosis and monitoring
The diagnostic approach proposed for confirmation of dry eye disease (DED) in the TFOS DEWS II report involves a screening questionnaire and measurement of various homeostasis markers, including non-invasive tear break-up time, tear film osmolarity and ocular surface staining [
]. Due to the placement of contact lenses on the ocular surface, contact lens-related technology has the potential to provide additional clinical information to aid in the diagnosis and monitoring of DED. A full description of the ocular surface anatomy, which may be useful to refer to, is given in the CLEAR Anatomy and Physiology of the Anterior Eye report [
]. Point-of-care osmometers, based on lab-on-a-chip technology, are now available that measure the osmolarity of microscopic tear film samples using electrical impedance [
]. Given the importance of osmolarity to the development of DED, a number of research groups have studied the feasibility of measuring this via contact lens technology. Researchers have developed a prototype contact lens which can evaluate tear osmolarity, tear evaporation rate and ocular surface temperature [
]. The authors aim to apply this technology in a clinical setting to assist in DED diagnosis, evaluate the effectiveness of clinical treatments and monitor clinical performance. This approach has the advantage of providing a continuous assessment of these clinical metrics. However, it is relatively complex, requiring external power induction and the integration of complex electronics within the contact lens.
An alternative approach to determining the electrolyte composition of the tear film uses coloured or fluorescent dyes that are integrated within the contact lens material. A microfluidics system has been developed [
], where a number of fluorescent chemical sensors were multiplexed in cavities engraved into a scleral lens. A handheld fluorescence imaging device was also developed to read the sensors and provide quantitative measurements. A similar approach has been used [
], where a hydrophobic ion-sensitive fluorophore was bound into commercial silicone hydrogel lenses, allowing individual ion concentrations in tears to be quantified. These fluorophore-based systems appear to avoid much of the complexity of an electronic sensor approach and are more specific about the concentration of each ionic species in tears than conventional osmometers. However, significant clinical work is required to better understand how these sensors would work in the chemically complex tear film environment, to review the safety of these dyes in a clinical setting and to understand how these dyes might otherwise influence clinical performance.
Finally, holographic grating sensors, which have previously been used to monitor analytes such as metal ions, glucose, water content and pH, have also been proposed as contact lens osmolarity sensors [
]. When a holographic sensor comes into contact with its analyte, the polymer within the sensor grows or shrinks, resulting in a change in the colour of the hologram (with the wavelength of the reflected light proportional to the analyte concentration). Holographic sensors can be produced on a commercial contact lens by direct laser processing for the sensing of sodium ion concentrations [
]. This approach is appealing as these sensors are purely optical, relatively low cost, compatible with hydrogel lens materials and require no complex electronics. However, they are yet to undergo any significant clinical evaluation and it is not fully understood how they are likely to perform in the biologically complex tear film environment.
3.2.2 Inflammatory cytokines and other biomarkers
In DED, a range of cytokines/chemokines are elevated in the tears, including TNF-α, IL-6, IL-17a and IL-8 [
]. Although no contact lens-integrated cytokine sensor currently exists, the feasibility of integrating antibody functionalised sensors into thin flexible polymer membranes for continuous studying of analytes (in this case monitoring IL-6 using a wearable diagnostic sweat biosensor) has been described [
]. This type of technology, integrated into a contact lens, would allow the development of a continuous monitoring system for tear film cytokines, in addition to point-of-care diagnostics, both potentially useful tools in the diagnosis and monitoring of DED, contact lens discomfort and other ocular surface diseases.
Immunoglobulin proteins found in the tears are also known to vary in concentration in a range of ocular surface diseases [
Pathological consequences of anti-citrullinated protein antibodies in tear fluid and therapeutic potential of pooled human immune globulin-eye drops in dry eye disease.
]. The binding of IgG to these photonic sensors results in a refractive index change, with a change in colour from green to red with increasing IgG concentration. This type of photonic crystal sensor is simple, low-cost, label-free and requires a simple imaging system for the detection of immunoglobulin proteins, meaning that it is well suited to point-of-care testing. This technology could also potentially be integrated into contact lenses to form wearable biosensors [
An alternative approach for tear film biosensing is the use of contact lenses to collect biomarkers for point-of-care diagnostics. An example of this approach is the development of a portable reader to quantify lysozyme, using a contact lens as the sample collector [
]. An example of this system has been described in the literature, where a balafilcon A lens was worn for 15 min and then washed in a microtube containing a reaction buffer. The lens was then discarded and the solution mixed with a fluorophore, with the fluorescence monitored over time using a mobile phone-based well-plate reader. The presence of lysozyme in this assay reduces the degree of fluorophore quenching, with the degree of fluorescence proportional to the activity of lysozyme. This type of point-of-care technology could enable the clinician to diagnose and monitor diseases such as dry eye or Sjögren's syndrome, where reduced concentrations of tear film proteins such as lactoferrin and lysozyme occur [
]. In addition, this technique could be adapted to detect the presence of pathogens such as Staphylococcus aureus, viruses that cause conjunctivitis or Acanthamoeba [
]. Indeed, it may be that the material and/or design of a contact lens could specifically be developed to extract analytes of interest from the tear film, particularly where they are present in only trace quantities. This point-of-care approach has the potential for advanced health diagnosis and monitoring and for personalised medicine-related applications.
3.2.3 Blink monitoring, material dehydration and ocular surface temperature
Blinking frequency and completeness are known change during contact lens wear [
]. Although blinking can be studied in a clinical setting, the integration of a blink sensor within a contact lens would allow continuous monitoring of blink dynamics whilst undertaking real-world activities. In addition to IOP monitoring, the commercially available Sensimed Triggerfish lens has been reported to be capable of tracking basic blinking characteristics during lens wear, due to a spike in resistance associated with blinking [
]. However, the increased thickness and modulus, and the invasive nature of the external antennae are likely to interfere with natural blinking dynamics. A contact lens-based blink monitoring system has been described [
], where transient reductions in light falling on an integrated photo-sensor would allow the frequency and completeness of eyelid blinking to be monitored, although this idea currently appears to be only conceptual in nature.
Another technology with potential application in diagnosing and monitoring DED is a structurally coloured contact lens sensor to detect changes in moisture and pressure by altering its colour [
]. These lenses were manufactured by dispensing silica particles onto the concave section of the contact lens mould, forming a highly ordered ring-like crystalline template, which was then polymerised into a hydrogel contact lens material. The contact lens was then placed in acid to etch the silica particles and subsequently washed with deionised water. The resulting contact lens had an inverse opal structure and displayed brilliant colour in the lens periphery. During material dehydration, polymer shrinkage reduces the spacing of the inverse opal structures, with the lens periphery displaying a visible shift in colour, which can be quantified using a spectrophotometer. In addition, the material is sensitive to pressure, due to the associated decrease in structure spacing, leading to a decrease in the reflectance wavelength. This may have diagnostic value in highlighting surface desiccation and/or increased pressure applied to the contact lens due to inadequate lubrication in DED (in addition to the potential of monitoring IOP). Although these devices have yet to undergo clinical testing, their simple approach to measuring the variation in hydration and pressure, suggests that this type of sensor holds promise for point-of-care diagnosis and monitoring of conditions such as DED and contact lens discomfort.
Ocular surface temperature has also been studied in relation to DED, as an unstable tear film is thought to increase tear film evaporation, resulting in a relative cooling of the ocular surface [
]. An optical temperature sensor has been developed, where temperature-sensitive liquid crystals incorporated into a contact lens exhibited a fully reversible temperature-dependent colour change [
H.J. Lai. System for measuring and analyzing ocular temperature, receiving analyzer and methods for using the same. Google Patents. US9642533B2. USA: Ubiquity Biomedical Corp; 2017.
] relates to the incorporation of an electronic temperature sensor into a contact lens, with the change in temperature over the interblink period reported to be useful in diagnosing DED. Depending on the placement of these sensors, it may be possible to independently sample the temperature of the underlying ocular surface (which is potentially raised in DED due to inflammation) and the temperature at the contact lens/pre-lens tear film interface (which is potentially reduced in DED due to evaporative cooling).
3.3 Monitoring of ocular vasculature
Monitoring of the vascular system is critically important in the medical management of a wide range of health conditions. Historically, devices to measure characteristics such as heart rate, oxygen saturation and the hyperaemic response of tissue were medical instruments, but this technology is increasingly being found in consumer technology, such as mobile phones and wearable technology. The eye is an ideal site to monitor the vascular system, as it allows an unobstructed view of the blood vessels in both the retina and conjunctiva.
3.3.1 Retinal vasculature
Typically, retinal imaging is performed using ophthalmic instrumentation in a clinical setting, but a recent patent [
] has proposed the incorporation of an ultrasonic transducer within a contact lens to allow retinal vascular imaging during wear. This patent describes the incorporation of an annular ring within a contact lens, which would contain the power system, control electronics and a piezoelectric element, whilst allowing the central portion of the lens to be transparent. The device would emit an ultrasonic pulse that would travel through the ocular media towards the retina. The returned ultrasonic signal would then detect pulsation of the retinal vessels and generate an image of these vessels. It is primarily envisaged that this technology would be applied to monitor general vascular health, with warnings provided to the wearer if the device detected a cardiac rhythm and/or rate of blood vessel displacement outside of a normal range. The patent also discusses its potential for monitoring ocular disease by analysing specific regions of the retinal vasculature, such as the macula or optic nerve head. Such data could either be continuously logged for later review by the clinician, provide live alerts to the wearer (either wirelessly or via an audio/visual alert via micro-acoustic/micro-photonic elements) or communicate directly with a concurrent drug delivery apparatus. Although there are numerous technical challenges in developing such a system and the patent seems to report on a concept rather than a working model, it does highlight the potential for an electronically active contact lens to monitor retinal vasculature.
3.3.2 Conjunctival response to contact lens wear
Conjunctival blood vessels are typically evaluated during an ophthalmic examination, with hyperaemia associated with ocular disease, inflammation and irritation [
]. A patent describes the incorporation of an optical sensor within a contact lens, which emits light onto the conjunctiva to allow detection of characteristics such as pulse rate and blood oxygen levels [
H. Ho, B. Amirparviz. Contact lens with integrated pulse oximeter. In: Office UP, ed. Google Patents. US8971978B2. USA: Verily Life Sciences LLC; 2012:25.
]. Although the proposed device is primarily intended for monitoring systemic vascular characteristics, this type of device has a range of potential uses in monitoring ocular health, including detecting hyperaemia of the bulbar and/or tarsal conjunctiva. Monitoring hyperaemia in a continuous fashion would allow a clinician to review changes in vasculature over a prolonged period of time to more appropriately manage a range of clinical conditions, including allergic conjunctivitis, DED, uveitis and contact lens complications. In addition, the device could either highlight to the lens wearer if hyperaemia was detected (via a visual or auditory stimulus [
H. Ho, B. Amirparviz. Contact lens with integrated pulse oximeter. In: Office UP, ed. Google Patents. US8971978B2. USA: Verily Life Sciences LLC; 2012:25.
]), could prompt a consultation with their eyecare practitioner (ECP), or act as a trigger to dispense a therapeutic agent from a drug-delivering contact lens.
The range of approaches and technologies currently being studied as potential contact lens and point-of-care biosensors highlights the huge interest in the area. These biosensors, however, should not necessarily be viewed as independent technologies, as it is likely that many of these sensors provide complementary information and, in the future, these differing technologies may be brought together into a single diagnostic lens, with the capability to monitor a wide range of characteristics. Alternatively, key biosensors may be incorporated into standard contact lenses as a routine feature of the lens, such as is now the case with ultraviolet blockers or lens inversion indicators.
4. Treatment and management of ocular conditions
The use of contact lenses in the treatment and management of ocular diseases is a relatively routine part of clinical practice. From providing pain relief in cases of corneal abrasion, corneal protection for trichiasis, to promotion of wound healing in neurotrophic keratitis, contact lenses are employed by clinicians for a broad variety of anterior segment conditions. However, the application of contact lenses for disease indications beyond what is currently undertaken in clinical practice has been a subject of significant research. The CLEAR Medical Use of Contact Lenses report provides a detailed review of the use of other aspects related to this section [
Dry eye disease is one of the most common conditions managed by ECPs and some novel contact lens options offer alternatives to the use of traditional therapies such as ocular lubricants. However, to date all of the options described have little, if any, clinical data to support their use in the management of DED and further clinical studies are required.
4.1.1 Dehydration resistant materials
A novel approach to avoiding ocular surface desiccation is the use of electro-osmotic flow [
]. This involves using an ionic contact lens material (such as a HEMA/methacrylic acid (MAA) copolymer), which serves as the fluid conduit for electro-osmotic flow generation. The placement of an arcuate anode and cathode in the lens surface allows an upward electro-osmotic flow of tear fluid within the contact lens when an electrical current is applied. This electrical current could be applied either by wireless induction or using biocompatible battery technology. The laboratory prototype described appears able to compensate for evaporative water loss and maintain post-lens tear film thickness by driving fluid flow through the lens material.
Another potential method to minimise dehydration is based around the use of an ultra-thin graphene layer on the anterior lens surface [
]. Graphene has long been hailed as a ‘wonder material’ and its possible uses in the field of contact lenses include its potential to act as an electromagnetic interference shield [
]. In its application to combat desiccation, the applied graphene layer is proposed to act as a barrier to water loss from the contact lens material. In DED, the ocular surface typically shows signs of desiccation due to an unstable tear film, infrequent or incomplete blinking and subsequent air exposure [
]. Therefore, an engineered material that is resistant to dehydration does offer a potential solution.
4.1.2 Lacrimal gland stimulation
An alternative approach to the treatment of DED focuses on increasing tear production by incorporation of an electrical stimulator into a contact lens. This concept is based on a similar intranasal stimulator technology (TrueTear, Allergan, CA, USA) which delivers an intranasal electrical stimulus to stimulate tearing [
]. The patent details the incorporation of a stimulator chip, which would generate an electric waveform to stimulate the cornea, conjunctiva and/or sub-conjunctiva, resulting in activation of reflex pathways and an associated increase in tear production [
]. The proposed design is envisaged to receive energy wirelessly from an external power source, potentially in the form of an external infrared light source and a contact lens mounted photodiode. To date, this appears to be conceptual, with no publicly available clinical studies. It is unclear whether such technology would produce a sub-threshold stimulus or whether the stimulus would be felt by the wearer, as is the case with the TrueTear stimulator, and whether the stimulus would be continuous or intermittent. Clinical evidence does support this neurostimulation approach to enhancing tear secretions [
] and therefore if a compact and comfortable contact lens-based treatment could be developed this would be exciting technology, offering an alternative option to new and existing contact lens wearers struggling with dryness symptoms.
4.1.3 Scavenging of reactive oxygen species and matrix metalloproteinases
Oxidative stress and the presence of reactive oxygen species at the ocular surface have been proposed to play an important role in the development of DED [
Results of a multicenter, randomized, double-masked, placebo-controlled clinical study of the efficacy and safety of visomitin eye drops in patients with dry eye syndrome.
Results of a multicenter, randomized, double-masked, placebo-controlled clinical study of the efficacy and safety of visomitin eye drops in patients with dry eye syndrome.
], has recently been described. Unlike antioxidant therapeutic drops that can potentially act on intracellular reactive oxygen species, these antioxidant nanoparticles are tightly embedded within the lens matrix, exhibiting their effects through the reduction of extracellular reactive oxygen species levels. These lenses exhibited good transparency, biocompatibility and effective extracellular reactive oxygen species-scavenging properties in an ocular surface animal model [
Another group of biomarkers commonly observed in ocular surface disease are the Matrix Metalloproteinases (MMPs) and a potential treatment in these conditions is the topical application of MMP inhibitors [
]. Sequestering of zinc results in a loss of essential ions from MMPs, resulting in their deactivation and this technology has the potential to treat conditions associated with excessive MMP activation, such as that found with increased amounts of MMP-9 in DED [
An intact and healthy corneal epithelium is required to achieve an effective barrier against infection and maintain the transparency required for clear vision. To achieve this, the epithelium is continuously regenerated by the limbal epithelial stem cells. Destruction of the stem cell niche in conjunction with dysfunction or depletion of the limbal epithelial stem cells, through trauma or conditions such as aniridia, leads to limbal stem cell deficiency, a debilitating condition characterised by painful chronic ulceration, inflammation and vascularisation of the cornea. Limbal stem cell deficiency may be managed by using scleral lenses, as outlined in the CLEAR Scleral lenses and CLEAR Medical use of Contact Lenses reports [
]. Conventional corneal grafts are typically ineffective for managing limbal stem cell deficiency and the therapeutic aim is to boost the limbal epithelial stem cell population through transplantation of donor tissue [
]. However, this method risks damaging the limbal epithelial stem cell population in the donor eye if the fellow eye of the recipient is used in unilateral cases of limbal stem cell deficiency, or graft rejection and the need for immunosuppression if a non-self donor is used [
]. The use of contact lenses as a stem cell delivery device has been demonstrated, with the contact lens vehicle doubling as a protective bandage following grafting [
Contact lenses are beneficial in that they are synthetic and non-immunogenic, eliminating the xenobiotic infection risk from donor tissue. However, the risk of infection resulting from overnight contact lens wear should be considered and to date, no clinical trials have compared the delivery of stem cells via contact lenses and amniotic membrane, and this is warranted before large-scale implementation can take place.
4.3 Pupil or iris defects
Liquid crystal cells have been recently combined with miniaturized electronic circuits forming smart platforms in order to replicate the functionality of the pupil and iris arrangement [
]. This may be useful for iris defects (aniridia and coloboma), transillumination of the iris (ocular albinism), high order aberrations (keratoconus) and high sensitivity to light (dry eye syndrome and chronic migraine). Such devices are intended to enhance the iris functionality by filtering incoming light autonomously controlled by application specific integrated circuits and on-lens light sensors and power directly by near magnetic fields and rechargeable micro-batteries [
The smart platforms are build-up by means of microsystems technology (photolithography, sputtering, etc.), flip-chip of discrete components and thermoforming into a spherical shape fitting the contact lens body [
]. The platforms can be embedded inside soft contact lenses, thus avoiding contact with the surface of the eye and maintaining the conventional refractive correction of the ophthalmic device [
]. Contrasts of 1:2 between ON/OFF (effectively blocking 50 % of the light at least between wavelengths of 500 nm and 600 nm) were able to be achieved, producing a pin-hole effect, and simulated results of the light filter with a 2 mm pupil diameter embedded inside a scleral contact lens with data from patients with aniridia gave maximum depth-of-focus values of 3D, 2D and 0.75D for light levels of 1000 cd/m2, 10 cd/m2and 1 cd/m2 [
]. Contrast values higher than 1:2 will be required in order to protect eyes with big pupils from excessive light.
4.4 Diabetic retinopathy
Diabetic retinopathy is the leading cause of blindness in the working age population and is a disease of ischemia leading to microvascular retinal damage. Oxygen consumption of the rod photoreceptors is greatest during dark adaptation [
]. This novel silicone elastomer contact lens incorporates 24 radioluminescent gaseous tritium light sources arranged in a radial pattern, with a clear central 3 mm aperture. This design allows unobstructed vision under photopic conditions, whilst under scotopic conditions the enlarged pupil allows the retina to receive the phototherapeutic dose.
The tritium light source is well suited to use in a contact lens, due to its compact size (300 μm by 2000 μm), safety profile (it emits no ionising radiation) and long life (12-year half-life). The therapeutic benefit of this concept is debatable, with electroretinogram testing in an animal model highlighting suppressed rod dark adaptation with this contact lens technology, whilst a large multi-centre randomised clinical trial, evaluating a similar mask-based technology, found no therapeutic benefit [
Clinical efficacy and safety of a light mask for prevention of dark adaptation in treating and preventing progression of early diabetic macular oedema at 24 months (CLEOPATRA): a multicentre, phase 3, randomised controlled trial.
]. This contact lens approach, however, has several advantages over the mask-based system, as the lens moves with the eye, avoiding issues associated with Bell’s phenomena, the light does not pass through the lid (thus the light intensity reaching the retina is more consistent), the presence of light is less bothersome (due to Troxler neural adaptation) and the wavelength better controlled [
]. Future clinical trials are clearly required to investigate whether this contact lens-based approach is able to reduce the long-term risk of diabetic retinopathy and diabetic macular oedema.
4.5 Colour vision deficiency
Colour vision deficiency is the result of an abnormality or absence of one or more of the three classes of cone photoreceptors in the normal human retina that are responsible for the perception of colour. Having abnormal colour vision may impact virtually all facets of modern life from childhood to adulthood, with implications extending across sports, driving, education, occupation and health and safety issues. For these reasons, exploring and understanding technologies that remove some of these limitations are of keen interest.
Enhancement of colour perception in patients with colour vision deficiency has been mostly limited to using colour filters, which enhance colour discrimination by tuning the brightness, saturation and hue through selective absorption of certain wavelengths. The first contact lens example to use this concept was the X-Chrom lens, a red contact lens placed over one eye [
]. This long-pass filter works by darkening yellow-green objects and making orange objects appear more red and slightly darker and appears more effective for anomalous trichomats than dichromats [
]. Tint selection is based on patient subjective response and their use significantly reduced error rates on Ishihara plates, the D-15 test, and an improvement in subjective colour perception, though it did suffer from reports of poor vision in dim light [
]. A large-scale plasmonic metasurface was embedded on a rigid corneal contact lens to address deuteranomaly, the most common class of colour vision deficiency. These metasurfaces are engineered surfaces made of subwavelength building blocks that enable a tuneable control over their optical response, in this case, utilising the wavelength-selective features to overcome colour vision deficiency. The fabrication process utilises an electron beam lithography technique to fabricate a 40 nm thick metasurface of gold building blocks on an indium-tin-oxide-coated glass. A thin (∼350 nm) layer of polymethylmethacrylate (PMMA) is then spin-coated and subsequently baked onto the metasurface and hot, deionised water is used to separate the PMMA matrix (with the embedded metasurface) from the glass substrate. This membrane is then thermally fused to a plasma-treated rigid corneal lens. Using a variety of matrices, researchers were able to demonstrate a shift in the perception of a test pigment in the case of deuteranomaly closer to the pigment viewed in cases of normal vision, as was contrast restoration using a simulated Ishihara plate perception test [
Clinical evaluation of commercial filters designed to enhance colour discrimination or “correct” colour vision deficiency indicates either no enhancement or substantial performance trade-offs. As a result, the potential benefits of the application of spectral filtering to mitigate colour vision deficiency are uncertain. Moreover, subjective anecdotes indicate that some colour vision deficiency subjects appreciate certain spectral filters, but the mechanism is not well understood. The metasurface contact lens technology holds some promise in that it may allow “tuneable” spectral filtering functionality into contact lenses to achieve an improved success rate over a range of patients with colour vision deficiency.
5. Drug delivery to the ocular surface
Drug releasing soft contact lenses have been widely studied and continue to show promise, primarily by overcoming the current limitations associated with delivering ophthalmic medications via an eye drop.
The primary disadvantage with eye drops is their low bioavailability of less than 5% [
], which is attributed to high tear turnover rates, blinking, nasolacrimal drainage, non-productive absorption by the conjunctiva, and low permeability of the cornea [
]. Thus, improving bioavailability by increasing the residence time of the drug on the ocular surface remains an important area of research. When placed on the eye, a contact lens splits the tear film into the pre-lens tear film overlying the lens and post-lens tear film (PoLTF) between the back surface of the lens and the ocular surface. This compartmentalisation is beneficial to drug releasing contact lens as the PoLTF is very thin with a relatively low turnover rate [
]. When a drug releasing lens elutes its medication into the PoLTF the low tear turnover rate promotes an increased concentration of the drug behind the lens, in addition to an increased residence time, leading to potentially greater bioavailability of the drug and increased ocular penetration [
], provided the drug volume and release profile is consistent from lens to lens. Once the lens is placed on the eye, the medication will elute from the lens with few external factors influencing the release profile. Contrary to this, there are multiple factors that can affect the variability of dosing via eye drops. With conventional eye drop bottles, patients are required to tilt their head back and keep their eye open while simultaneously positioning the inverted bottle directly over their eye and squeezing the dropper bottle with the precise amount of force and with accurate aim in an attempt to deliver the prescribed amount of medication. Not only is there variability in how successful patients are in their aim but also in the drop size itself based on the bottle tip, amount of drug in the bottle and angle at which the bottle is held [
Incorporating drug-releasing technology into a soft contact lens may also significantly improve treatment compliance over eye drops. The compliance rate with the routine administration of eye drops is low [
] and while the reasons are likely multifactorial, patients may simply have difficulty incorporating their eye drop therapy into their daily routine. However, assuming a contact lens technology can provide a sustained release over multiple days, a patient can wear the lens (or have it applied for them) and have their medication continually delivered over a predetermined period of time. If a drug releasing contact lens is loaded with a daily dose of medication, the vision correction function of the contact lens may improve compliance, particularly in habitual contact lens wearers, as inserting contact lenses are already part of their daily routine.
Many topical ophthalmic drops require preservatives such as benzalkonium chloride to provide antimicrobial protection and maintain drug stability. However, even at low concentrations they can result in corneal and conjunctival epithelial cell toxicity [
]. Contact lenses are terminally sterilised and so the use of preservatives with drug-releasing contact lens technology is not required.
5.1 Challenges to contact lens drug delivery
While there are potential benefits to delivering ophthalmic medications via a contact lens, there are many challenges that must be overcome for this technology to become a commercial reality.
5.1.1 Choosing a lens/drug combination to optimise the uptake and release profile
The first consideration is in selecting the specific drug and contact lens material that will allow for a therapeutically meaningful uptake and release profile. A key attribute of the drug under consideration is its chemical nature. A more hydrophilic molecule will be more easily incorporated in a more hydrophilic hydrogel lens material, while a more lipophilic molecule will be more easily absorbed by a relatively hydrophobic silicone hydrogel material. However, if a drug molecule has an exceptionally high affinity for the lens material, then it could result in an unacceptably prolonged drug release profile once the lens is placed on the eye [
The efforts to identify various technologies to influence drug uptake and release from a contact lens have led to some compelling results from in vitro experiments. However, it is important to note that the correlations between in vitro models and in vivo results are not always strong, due to the difficulty in simulating continuous tear flow, eyelid blinking mechanics, and the morphology of the ocular surface. Thus, the drug release kinetics demonstrated in the laboratory may not be replicated when the drug releasing lens is placed on the eye [
On the path to commercialisation, once the specific drug and contact lens material has been selected and an optimal method for incorporating the drug into the lens matrix obtained, the combination must remain viable throughout the lens manufacturing process. The drug can be incorporated into the lens monomer mix, facilitating a relatively homogenous distribution throughout the manufactured lens. However, this requires that the drug withstand the lens curing steps (typically via a light or thermal curing process). Once cured, the lens then typically goes through a series of monomer extraction and lens hydration steps using aqueous and/or solvent solutions. Depending on the chemical nature and stability of the drug, these curing and extraction steps could have a significant impact on the final loaded drug concentration or may even accelerate drug degradation. To protect the drug from the lens manufacturing environment, the drug could be added after the lens has been fully polymerised and hydrated. In this scenario, the challenge is then to find the optimal method of drug incorporation, resulting in the desired drug uptake and release profile, in addition to incorporating a consistent amount of drug within the lenses. Finally, since most contact lenses are terminally sterilised via an autoclaving process, the selected drug would ultimately need to be able to withstand a period of intense heat (over 120 degrees Celsius).
5.1.3 Impact of lens design on drug uptake
While the consistent release of the drug is a key benefit of a drug releasing contact lens, a prerequisite of this is that a consistent amount of drug is taken up by the lens. The challenge in this comes from the multiple lens designs and range of lens powers that are required to provide this vision-correcting technology to a broad patient base. The different lens powers require subtle differences in lens shape, resulting in a change in lens volume. For example, a hyperopic lens has a greater centre thickness than a myopic contact lens. Similarly, the designs for toric contact lenses often have an increased thickness profile across specific regions (due to the stabilisation zones) as compared to a spherical power lens. Thus, to maintain a consistent and efficacious dose being released to the eye, the drug uptake must be tailored to each lens power and lens design during the manufacturing process, which is complex and likely to add cost and time to the production process.
5.1.4 Impact on contact lens properties
The incorporation of a drug into a contact lens cannot significantly alter the contact lens properties and parameters or have a detrimental impact on comfort, vision and handling. The tear film uptake profile is also an important consideration, as the chemical nature of the drug could result in tear film lipids and proteins to have a greater affinity to the lens. The lens also needs to maintain an acceptable base curve radius and diameter to ensure an optimal fit, as well as sufficient oxygen permeability based on the intended wear modality.
5.1.5 Regulatory issues
Another substantial hurdle relates to the clinical trials required to demonstrate the safety and efficacy of the drug releasing lens. The scope and timing associated with these trials can be influenced by multiple factors, including the disease state being evaluated, the endpoints required to demonstrate efficacy, the intended lens wear modality (such as daily wear or overnight wear), the existing safety profile of the drug and contact lens material, as well as the regulatory pathway for product approval, as combination products require both pharmaceutical and device review [
The lens wear modality of a drug releasing contact lens is obviously an important factor as it will dictate the required release profile necessary to provide a therapeutic benefit. For chronic disease states or patients who may otherwise not wear contact lenses, an overnight wear or monthly replacement daily wear modality may seem logical. In these cases, the drug release profile would be tailored to elute the medication over multiple days or weeks. However, if intended to be worn on an overnight wear modality, the drug releasing lens would likely require extensive clinical testing to support an acceptable safety profile [
]. If the lens is designed for a frequent replacement, daily wear modality, then the drug-lens combination would need to be able to withstand the daily rubbing, rinsing, and overnight soaking steps associated with the use of multipurpose cleaning and disinfecting solutions. A daily disposable lens wear modality may provide some advantages by avoiding the interactions with lens care solutions, but to be commercially viable, the manufacturing process would need to be scaled up to allow for a sufficient quantity of lenses to be produced.
5.1.6 Long-term stability
A packaged drug-releasing contact lens is required to demonstrate long term stability with minimal drug degradation and with a consistent amount of drug in the lens over time [
]. This can be challenging, as soft contact lenses need to remain hydrated and are usually immersed in solution in their primary packaging container. Once manufacturing and packaging are complete, the lenses are then shipped and stored in distribution centres, ECP offices, or in patient’s medicine cabinets for many months prior to use. During this time, the medicated lenses can be exposed to a wide range of temperatures, which can impact the stability of the product. Therefore the packaging solution and primary packaging must be compatible with the drug-lens combination to protect it from degradation over time [
A wide variety of technologies have been established in an attempt to develop commercially viable methods to deliver drugs to the ocular surface from contact lenses.
5.2.1 Contemporary contact lens materials
Contemporary contact lens materials are commonly used as part of the therapeutic management of conditions such as corneal abrasions and recurrent corneal erosions via their so-called use as “bandage lenses” [
]. Despite this common clinical practice, few studies have investigated the impact of concurrent pharmaceutical and contact lens use on clinical outcomes or safety, or of the degree to which topical drugs are delivered to the eye when combined with commercially available contact lens materials.
Almost every major class of ophthalmic medications in use has been investigated in vitro for their uptake and release into commercially available contact lenses, from anti-allergy [
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