Few areas of optometry evolve with the same rapidity as the world of contact lenses. Yet, despite the apparent speed of change, as signalled by growing product portfolios, behind the scenes developmental pipelines are often protracted with a need to overcome both technical and regulatory hurdles.

In this article we consider, in brief, the recent and expected future changes to contact lens categories, the supportive evidence and future challenges.

Drug delivery through contact lenses 

Eye drops can be an ineffectual vehicle for ocular drug delivery.  Immediately upon instillation, drops will enter the lacrimal drainage system, dilute in the tears, and disperse across the ocular surface and inner eye lids. Thus, the amount of drug reaching the intended site of action, ie the bioavailability, can be limited.1-2 

To obviate the risk of drug loss, an intuitive response may be to simply increase eye drop volume, however, the rich vasculature and larger surface area of the conjunctiva and surrounding ocular adnexa offer a diversion away from the cornea and a route into systemic circulation. Consequently, the risk of systemic adverse effects and interactions with other drugs may be increased.2

Another common obstacle is poor patient compliance, which may present a concern especially where repeated doses or multiple types of eye drops are required throughout the day. 

Despite their shortcomings, eye drops remain the main method for ocular drug delivery; they are minimally invasive and can be self-administered unlike, for example, intraocular injections. Alternative topical drug delivery methods, such as ocular ointments, are beneficial for drug retention but can lead to temporary visual annoyance due to their high viscosity.3 Systemic approaches have difficulty crossing the blood-aqueous barrier, and so higher drug doses are required to achieve the desired concentrations within the eye; a process which also increases risk of systemic toxicity.4

A potentially more efficacious approach could be in the form of drug releasing contact lenses. The proximity of the lens to the cornea could help improve bioavailability, while affording additional benefits such as dosage modulation and, if the patient is already a contact lens wearer, a potential for improved compliance.  

Methods of drug release through contact lenses
Drug delivery through contact lenses has, until recently, proven elusive. Success depends upon lens properties (eg ionic charge, hydrophilicity), features of the drug (eg molecular weight, solubility) and how they interact with one another.2 In theory, the drug will be released from the contact lens into the post lens tear film, where minimal tear exchange should prevent the drug from washing away and thereby improve drug retention times.5 In actuality, impregnating a contact lens with a specific drug, with a slow-release mechanism, which has neither a deleterious effect upon optical performance, oxygen permeability or comfort is a challenging feat.

Some of the past and current approaches for contact lens drug release are summarised below.

  • Soaking: Commercially available contact lenses are soaked in the drug solution.  Depending on the drug/lens material affinity there is potential for a ‘burst release’ effect for low affinity combinations, alternatively, a prolonged drug release delay for high affinity combinations. Other factors, such as drug concentration, will also affect drug release kinetics.6-7
  • Molecular imprinting: A process by which memory sites that mimic the drug’s natural receptors are formed (imprinted) within the lens.6,8 Soaking the lens in the drug saturates these sites.9 Benefits may include greater loading and a slower drug release.10 With reusable lenses, to maintain similar levels of daily drug doses, the lens must be thoroughly cleaned to remove any residual drug solution before being reloaded for the next wear.
  • Drug reservoirs: Biodegradable polymers containing the drug, that can be tailored to modulate drug release, are incorporated into the lens. Typically, these are positioned in the lens periphery to avoid interfering with the central lens optics.6 
  • Drug release barriers: A barrier, such as vitamin E, is added to extend the path that a drug must follow prior to release, thus extending the drug release time.6,11-12 Some barriers are added as layers within which the drug is held, this can also help increase drug loading. Interactions with the tear film and blinking lead to drug release from these layers, with the slowest release originating from the innermost layers and the most rapid from the outer layers.13
  • Nanoparticle integration: Nanoparticles, that have a high affinity for a specific drug, are incorporated throughout the contact lens. Some of these nanocarriers are biodegradable, therefore degradation will lead to drug release, others make use of external stimuli such as light or temperature changes to elicit drug release.14
  • Material ionic charge: The ionic charges of a drug and lens influence drug loading and release. The lens material charge can be manipulated to align with the drug of choice.13,15

Challenges 
Drug release profiles continue to be one of the fundamental issues with drug eluting contact lenses. If a drug that typically requires multiple timed doses is released too rapidly (a burst release), then the individual may need to replace their contact lens in time for their second dose, clearly negating any convenience benefits afforded by drug release lenses. A summary of some of the obstacles encountered by researchers is listed in figure 1.

Figure 1: Obstacles faced by researchers investigating drug eluting lenses include issues relating to drug release kinetics, storage, drug stability, potential changes to lens dynamics, ocular comfort and visual experience2,6,7,13,14 

The present
Several different drugs, and many commercially available contact lenses,16 have been assessed for their viability in contact lens drug release. Applications have been proposed for both anterior and posterior eye diseases,17-19 each with differing levels of success. Not all attempts have been futile, products have reached late-stage clinical trials, but commercialisation has largely proven elusive. One product of note includes the antihistamine (ketotifen) releasing lens,16 which has demonstrated a positive impact on mean ocular itching scores compared to standard contact lenses.20-21

The future
As contact lenses that mediate drug release become more widely available, eye care practitioners (ECPs) may begin to consider the clinical and commercial implications of this novel lens category on their own practice. As yet, data on practitioner and patient views towards drug eluting lenses remains limited and the early evidence is mixed.22-25 Further work investigating safety, tolerability and efficacy could help in understanding the likely uptake by patients and practitioners.26 

Smart contact lenses 

Smart contact lenses have captivated the attention of audiences both within and outside the optometric profession. While part of the enthusiasm may be attributed to the involvement of technology conglomerates such as Google, it is also likely part of a broader trend towards wearable health technologies.27

A paucity of published scientific literature can make it difficult to look beyond the press releases, but patents and clinical trial registrations can offer some clues to the direction in which the field is moving.   

Methods by which smart contact lenses work
Contact lens developers can make use of various photometric, optical and bio-sensors to detect changes in the eye or visual environment. For example, piezoresistive sensors or strain gauges, can be used to detect pressure changes,28 ie a potential application for measuring intraocular pressure; and microfluidic sensors to detect changes in biological components such as enzymes or antibodies within the tears, ie a potential application in monitoring ocular infections and allergies.29 Multifunctional lenses that can monitor more than one disease are also in development, and the use of newer materials30 such as graphene is helping to move this field forwards.31

There are several lens subcategories that fall under the umbrella of the ‘smart lens’, a brief overview is provided below.

Disease monitoring lenses 

Diabetes
Compared to blood testing, disease detection through tears and contact lenses offers a relatively less invasive approach, with the added potential of providing more comprehensive clinical data, eg diurnal variations.32

To overcome the need for home finger-prick blood tests, companies such as Microsoft and Google have tried developing contact lenses for monitoring tear glucose levels.335

Several approaches have been proposed34-35 including use of graphene sensors;302 and boronic acid based attempts to develop lenses that fluoresce in the presence of raised glucose.36-37 Thus far, there seems to be little in the way of commercially available products. 

Intraocular Pressure (IOP)
The Sensimed Triggerfish contact lens is a FDA approved and CE marked device for measuring diurnal intraocular pressure fluctuations for periods of up to 24 hours, intended for use in individuals at risk of glaucoma.38 A strain gauge sensor, embedded within the soft disposable contact lens, detects changes in corneoscleral shape. Information is then sent wirelessly to an adhesive external antenna, attached near the eye, before being passed onto a wearable portable recorder.39 At the end of the recording period, the recorder data can be transferred to the practitioner. The intention is to monitor fluctuations in IOP; these are recorded in millivolts, unlike conventional IOP measurements which are recorded in millimetres of mercury, thus making it difficult to draw direct comparisons with conventional tonometry readings.40

Other novel proposals to measure IOP, using contact lenses, have included development of materials that change colour in response to pressure and moisture changes.41   

Dry eye
Dry eye related conditions are linked to the presence of various biomarkers within the tears.42-43 There is potential to both detect and treat dry eye conditions using smart contact lenses.41,44

There have also been reports that biomarkers for Parkinson’s disease, multiple sclerosis and possibly for some types of cancers may be present in the tears,45-58 thereby extending the diagnostic potential of smart contact lenses to beyond ocular conditions.49 

Enhancing vision 

Accommodative
In addition to disease detection, smart contact lenses have been used to enhance vision, including proposals to develop
accommodating contact lenses for presbyopes.   

While several approaches have been put forth50-52 one which is supported by growing research interest is the use of liquid crystal (LC) cells.51-53 A small change in voltage brings about large changes in refractive index and thus lens power. Activation could potentially be via an external device, eg a smartwatch, or possibly through deliberate blinking.54-56 

Digital smart lenses
Augmented reality, mixed reality and virtual reality, are terms found more often among tech blogs than the optical press (see figure 2), but this has gradually been changing over the past decade. Frequent reports of smart glasses and contact lenses detail prospective features that include displaying of digital alerts such as text messages, weather information and the potential to capture images and video recording. Several tech giants such as Sony and Samsung have been granted patents relating to smart contact lenses;57-58 with the most recent press releases reporting on a collaboration between Menicon and Mojo Vision.59

Figure 2: Augmented, virtual and mixed reality definitions62

 

In addition to the entertainment and novelty aspects, smart lenses also possess the potential to help aid navigation, object detection and to magnify aspects of the visual environment; all potentially useful applications for individuals with visual impairment.  

The delays in these, sometimes theoretical, products reaching the market are a likely mix of technical and regulatory challenges. The microelectronics need to be small and lightweight enough to not impede oxygen permeability, positioned to avoid negative impact on vision, while retaining lens dynamics and comfort. An added challenge is displaying the digital images in such a way that is both visible, but not obstructive.60-61

The future
Most smart contact lenses remain in a developmental stage.  While newer materials and technological advances may overcome any technical hurdles,31 wider discussions about privacy, safety, and the role ECPs might play, will all need to take place.

Myopia management with contact lenses 

It is reported that almost half the world’s population will be myopic by the year 2050;63 but a statistic of greater significance to practitioners in the UK and Ireland is that Western Europe is expected to reach this unfortunate milestone around a decade earlier. In fact, by the year 2030, an estimated ~45% of the population in Western Europe will have already become myopic.63

Axial myopia is attributed to a discord between increasing axial length and the refractive capabilities of the cornea and crystalline lens.64 Typically, a 1mm increase in axial length equates to approximately ~2.5 to 3DS of axial myopia,65-66 but differences can exist between different demographics. 

Earlier onset is often linked to greater risk of progression to higher levels of myopia.67 For most individuals, progression will stabilise by the late teens,68-69 however, an unlucky minority may continue to progress beyond this point.68-69 As myopia and axial length increase, so too does the risk of developing sight threatening disorders.70 Hence, inhibiting the onset of myopia, or at least minimising the risk of high myopia, could yield significant benefits.

The reasons underlying escalating myopia prevalence are believed to be multifactorial. Exposure to a myopigenic environment (a lack of time outdoors, near work, pursuit of higher education),71-73 may increase an individual’s risk of developing myopia, elements of which may be further compounded by an existing genetic predisposition.74

Theories of myopia development and progression are wide-ranging, but the design of many myopia inhibiting contact lenses relies, in some way, on the concepts of relative peripheral hyperopia (see figure 3) and/or accommodative lag.  

Figure 3: (a) Peripheral hyperopic defocus, relative to the central retina, is believed to influence central axial growth. Image shell falls behind retina for the peripheral region (b) Reducing this hyperopic defocus is believed to inhibit myopia progression

Methods of myopia management using contact lenses
While time outdoors may deter the onset of myopia, for individuals who are already myopic various myopia inhibiting solutions are gradually making their way to market. Current solutions include spectacle lenses, contact lenses and on the horizon is the potential for myopia specific pharmaceutical preparations.

Rigid gas permeable corneal lenses
Some older texts advocated the use of rigid corneal lenses to manage myopia, while this practice has now largely fallen out of favour it still persists in some parts of the world.75 There is, however, limited evidence of a genuine treatment effect.76 Any positive impact is thought to be linked to a mechanical flattening of the cornea rather than a slowing of axial elongation.76

Orthokeratology in myopia
Orthokeratology (OK) has long been used as a reversible non-surgical alternative to refractive surgery. Lenses are worn at night to temporarily reshape the cornea providing temporary relief from refractive error during the day.77-78 While in this article OK is referred to in the context of correcting myopic refractive error, the technique has also been used to correct hyperopic, presbyopic and astigmatic errors. 

OK affords freedom from spectacles and contact lenses during most waking hours, however, towards the end of the day corneal shape may begin to recover, causing a regression effect76-77 of around ~0.50-0.75D. To counter this, a small amount of overtreatment is often incorporated.78

OK (or reverse geometry) lenses are unlike the rigid corneal lens designs intended for daily wear. There is a greater need for high oxygen transmissibility; stability, to ensure the same part of the cornea is treated consistently and, of course, a requirement to temporarily reshape corneal geometry.79 The latter is achieved through use of a flat central base curve and the incorporation of a secondary lens curve that is relatively steeper than both the central and peripheral curves. This arrangement creates a tear reservoir or ‘reverse zone’ that facilitates lens stability while permitting rapid changes to corneal shape.

During lens fitting and aftercare appointments the cornea is closely monitored. Corneal staining and lens binding are common complications associated with OK,79,82 but among the most serious potential complications is microbial keratitis; the risk of which increases due to overnight lens wear.

It is now well established that use of OK can inhibit axial length increase and therefore impede myopia progression.76,81 While the mechanisms underlying this inhibitory effect are unclear, some researchers have attributed it to a redistribution of corneal cells, in which there is central corneal flattening, compared to relative steepening more peripherally.82 In line with the theories of peripheral hyperopia; changes to corneal morphology could, therefore, both reduce central myopia and induce peripheral myopic defocus.83 Others suggest an increase in higher order aberrations84 or changes to accommodative response may also play a role.85 

The introduction of OK lenses specifically for myopia management may signify the growing interest of manufacturers in this area of practice. Yet questions remain, including a need for further clarity and consensus around a potential rebound effect, the underlying mechanisms for the myopia inhibition effect and a need for longer-term data in some population groups.79

Soft contact lenses for myopia management
Until recently a lack of licensed soft lens products, for myopia management, led some ECPs to off-label prescribing of multifocal lenses intended for presbyopia. While these lenses generated pockets of impressive data, a published review of myopia management, that was limited to randomised controlled trials (RCTs), concluded bifocal soft contact lenses were of little benefit.76 Nevertheless, since this landmark review was undertaken, several key RCTs of soft lenses for myopia management have now been published, demonstrating an impressive slowing of both axial elongation and myopia using dual focus and extended depth of focus lenses.86-87 

Evidence is still emerging and recent work has shown how manipulation of the lens add can lead to further improvements in outcomes.76 Future developments may give rise to a broader range of myopia management options including greater soft lens provisions for myopic astigmats.

The future
Myopia management is an area of active development and while many of the previous barriers to uptake have now been addressed, gaps in the knowledge base remain. Not all practitioners will wish to undertake myopia control, but it is important for all to remain informed of the options so that patients can be appropriately advised.

In the future, there may be potential for contact lens ECPs to expand myopia management offerings through combination treatments, such as combined contact lens and low-dose atropine use.  

Photochromic contact lenses 

Visual discomfort or impaired visual performance attributable to a bright light source is referred to as glare. The impact of glare depends upon several factors including the intensity of the light source, the angular distance, ocular adaptive state and opacities in the optical media.88-89 

Glare may be broadly classified as either disability or discomfort glare; the former impairs an individual’s ability to see (eg the glare from oncoming headlights) and the latter causes discomfort compelling the individual to avert their gaze (ie photoaversion).89 The presence of glare and loss of contrast sensitivity is one of the reasons why despite demonstrably good visual acuities in the test room, some patients may experience poorer visual performance when undertaking real-life tasks.90  

Since their initial introduction in the late 1960s, photochromic spectacle lenses have become an integral part of the ophthalmic dispensing options on offer to patients. It has, however, taken a further ~60 years for photochromic contact lenses to become commercially available.  

While the inception of photochromic contact lens designs can be traced back to at least the mid-1980s,91-93 it was in 2018 that Johnson & Johnson Vision Care, Inc (in collaboration with Transitions Optical), secured FDA and latterly CE approval for their Acuvue Oasys with Transitions contact lens.94-95  

The lens works through the incorporation of a photochromic additive throughout the lens matrix.96 Changes in ambient lighting, specifically exposure to ultraviolet (UV) or high energy visible (HEV) light, bring about changes in the light transmitted by the lens. When fully activated (ie a darkened state) only 35±5% of visible light across the range 380-780nm will be transmitted; and 85±5% when minimally activated (ie a clear lens state).97 Product literature claims it can take less than one minute for the lens to activate in situ and around one-and-a-half minutes to return to its non-activated state.95 

Visual function with the lenses
Early studies have shown the lens can be successfully fitted to most neophyte contact lens wearers and compares favourably, or at least is demonstrably comparable to alternative standard optical corrections.97-101 The data also suggest the lens could be beneficial in both outdoor and,98 to a lesser degree, within indoor environments96,101 (see figure 4), ie beneficial even when in a minimally activated state.101 The improvements to indoor vision have, in part, been attributed to the lens facilitating adaptation to changes in perceived brightness.

Figure 4: Subjective assessment of visual performance with the photochromic contact lens compared to spectacles by neophyte contact lens wearers at five weeks follow up (four weeks of contact lens wear, followed by one week of spectacle wear, n=105) (based on data from Buch et al 2020)99

While objective visual performance with the lens is impressive, subjective assessment is also reasonable.96 Figure 4 shows the subjective responses of more than 100 neophyte contact lens wearers to photochromic contact lens wear over a four-week period, followed by a resumption of their habitual spectacle lenses. The largest positive gains were made for ‘soothing vision’, which was described by the authors as the ability to see comfortably under bright light. The least positive gains were made for ‘vision indoors’, but ~41% of respondents still noticed an improvement and around half reported vision to be similar.96

Driving
To date, only one study has investigated driving with the commercially available photochromic contact lenses.98 Driving performance, in both day and night-time conditions, was deemed non-inferior compared to standard clear contact lenses and to photochromic spectacles. While most parameters assessed showed no significant difference (eg lap time, hazard avoidance), one parameter that did show significant improvement with the lenses was the distance at which road signs were recognised; by an estimated 7.5m and 17.8m for both day and night driving respectively.98

Summary

The field of contact lenses continues to be an active area of development. In addition to this brief overview of new contact lens applications, additional opportunities and efforts to broaden contact lens practice are gradually reaching fruition, for example, a growing interest in telehealth,102 dry eye treatments103 and innovations in ocular imaging.104-105

When keeping abreast of changes in the field, ECPs should be cognisant of relevant professional guidance. Regulatory steps to bring a product to market exist, among other reasons, to establish product and patient safety. 

  • Dr Manbir Nagra is an optometrist, educator and researcher and a paid consultant for the Johnson & Johnson Institute, UK. Dr Rachel Hiscox is a Professional Education & Development Manager, UK & Ireland for Johnson & Johnson Vision Care.  
  • This article is part of a revised and updated ‘Essential Contact Lens Practice’ series, originally authored by Jane Veys, John Meyler and Ian Davies. This article was produced without further input or review from the original authors.

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