There have been dramatic increases in the prevalence of myopia in children and young adults during the past few decades.1,2 Myopia is now the most common refractive error in teenagers and young adults in most parts of the world.3 In addition, myopia is commencing at a much younger age in many countries.1 In the United States, myopia has doubled in the last 30 years.4 An earlier age of onset is linked to faster progression, which in turn contributes to increased myopia severity and a higher risk of associated ocular pathologies like cataract, glaucoma, and retinal degenerations.5,6
The purpose of this review is to speculate on future developments in contact lenses (CLs) to slow progression of myopia based on research trends in myopia control.
FACTORS DRIVING THE DEVELOPMENT OF MYOPIA
A rapidly growing body of research is revealing that susceptibility to becoming myopic is a complex and multifactorial subject.
Parental Influence and Ethnicity
It is well established that myopic risk increases with the presence of parental myopia, particularly when both parents are myopic, and there are indications that a positive parental history of myopia plays a predominant role in myopia of early onset between 6 and 14 years.7 A child with two myopic parents has a five to six times increased risk of becoming myopic compared with a child with one or no myopic parents.7–10 Ethnic background also plays some role in myopia susceptibility. In Australia, for example, East Asian children aged 11 to 15 years are eight times more likely to be myopic than their white counterparts.11 There is debate though about whether childhood myopia is inherited as a solely genetic susceptibility or if the influence of myopic parents in creating a myopigenic environment is more significant. Children of myopic parents have been shown to spend less time outdoors and more time reading than children of emmetropic parents,12 both of which are independent risk factors for myopia onset and progression.
Environmental susceptibility to myopia seems to be common across all ethnicities, and although some genetic myopic risk is likely, there is strong support in the literature for environment to be the major pervasive contributor to school-aged myopia.10
Performing prolonged near tasks, like reading and gaming on portable devices, increases the risk of myopia development in children of all ethnicities.13 The duration spent performing reading at very close distances has significant associations with the risk of myopia rather than total time spent on all near activities.13 Ethnic variations in time spent on near tasks can also correlate with myopia frequency—for example, Australian children of European white origin spend 20% less time on near work than their classmates of East Asian origin.12,13
Increased outdoor activity has been implicated as protective to myopia development. Children of any ethnicity with myopic parents spend less daily time outside than children without myopic parents.12 Myopia has been shown to progress more during winter months compared with summer months,14 and near work activity has also been shown to be unrelated to the development of myopia once outdoor activity is taken into consideration.15 In terms of mechanisms, an inverse association between sun exposure and development of myopia has been established,16 which is unrelated to the amount of physical activity.12,16
Peripheral Refraction and Myopia
Animal models have demonstrated the role of the peripheral retina in modulating eye growth17 and its dominance over conflicting foveal visual signals.18 There is evidence for a role of the peripheral refractive state of the eye in modulating eye growth. Although emmetropes and hyperopes exhibit peripheral myopia relative to their central refraction and an oblate ocular shape, in myopes, peripheral hyperopia is evident,19 along with a less oblate shape as myopia increases.20
When compared with age-matched emmetropes, children who become myopic demonstrate a higher relative peripheral hyperopic refraction from 2 years before onset of myopia, which is maintained through to 5 years of follow-up after myopia development.21 There is conjecture, though, as to how consistently relative peripheral hyperopia (RPH) influences myopia development and progression. Relative peripheral hyperopia in primary school-aged Asian children is related to teenage development of myopia, but not in white or Hispanic children.22 Relative peripheral hyperopia does not seem to change with increasing axial length or time from myopia onset, indicating that other mechanisms are involved in both the onset and progression of myopia.21 There is increasing scientific interest in modifying RPH in efforts to control myopic progression; however, the lack of a consistent causal link between RPH and axial elongation indicates that this is not the panacea to preventing myopia development or progression in children and young adults.21,22
Binocular Vision and Myopia
There is a reported association between higher levels of esophoria and accommodative lag at near in myopic children and young adults as compared with emmetropes.23,24 Myopic children and young adults also show insufficient accommodative responses to lens-induced blur,23,25,26 greater variability in accommodative response,27 reduced accommodative facility,24,26 and enhanced accommodative convergence (elevated AC/A ratios) when compared with age-matched emmetropes.28 Greater accommodative lag has been reported in young adults with progressing myopia compared with those with stable refraction.24 In children, accommodative lag was not significantly elevated during the year of onset of myopia but was higher after onset of myopia.29 Others have instead shown smaller lags of accommodation among emmetropic and myopic young adults in the subject cohort who developed the most myopia within 1 year.30
CURRENT CONTACT LENS OPTIONS FOR CONTROLLING PROGRESSION OF MYOPIA
Cho et al.31 in 2005 and Walline et al.32 in 2009 first reported 47% and 55% less axial elongation for 2 years of orthokeratology (OK) lens wear when compared with historical controls. More recent OK studies using concurrent controls conducted for periods of 2 to 5 years have shown a 32% to 42% myopia control effect from OK.33–36 Partial correction with OK has also been shown to be effective, with high myopes of 6.00D or more partially treated by −4.00D, showing a 76% reduction in myopia progression across 1 year compared with spectacle wearers.37 Orthokeratology induces relative peripheral myopia,38 which offers a reasonable mechanism of action. Orthokeratology-induced increases in positive spherical aberration (SA)39 and amplitude of accommodation40 have also been suggested as possible mechanisms for its myopia-controlling properties.
Studies conducted across longer time frames have given some understanding of the duration over which OK effectively provides a myopia-controlling effect. Across 5 years, Hiraoka et al.36 found that axial eye growth was significantly lower than spectacle lens wearers for the first 3 years. In a different study that did not directly measure myopia control because it did not include axial length measurement, cumulative clinical data for 62 pediatric OK wearers of at least 18 months’ duration demonstrated refractive stability—the group mean progression in myopic refraction did not reach clinical relevance (−0.25D) until 42 months of lens wear.41
In their crossover study comparing OK lenses worn overnight in one eye and rigid gas-permeable (RGP) lens during the day in the fellow eye, which were swapped after 6 months, Swarbrick et al.42 reported less axial eye growth in OK compared with RGP eyes. Through adopting a contralateral study design, their data revealed that the eyes swapped to RGP wear at 6 months, having not grown for the previous 6 months with OK wear, grew by approximately twice as much in the second 6-month period than had been seen for the fellow eye during the first 6-month study period. A similar rebound effect has been seen in pharmacological interventions when ceasing atropine resulted in higher rates of myopia progression compared with placebo.43 Swarbrick et al.42 concluded that 6 months of OK was insufficient for stable myopia control.
The outcomes from these studies suggest that OK is effective in slowing the progression of myopia for the initial period of wear and up to 3 years; however, they fail to answer how long wear needs to be continued thereafter to maintain effect and whether there is a rebound effect if wear is ceased.
A recent development has been an attempt to induce a multifocal OK profile as a means for the controlling progression of myopia. In a crossover study, Loertscher44 fitted children with a novel dual-focus multifocal OK lens design in one eye and a standard OK lens in the fellow eye. During a 26-day period, they reported short-term changes to ocular biometry in the multifocal OK lens–wearing eyes that could be considered antimyopic. Studies are now needed to see whether these short-term changes to ocular biometry will equate to slowing of myopia and axial eye length during the longer-term.
Multifocal Contact Lenses
Multifocal CLs are available in a number of different formats, and although principally designed for correction of presbyopia, simultaneous (also known as dual-focus) designs and aspheric designs have been shown to be influential in slowing the progression of myopia.45–49
In comparison with soft CLs, concentric bifocal CLs slowed the progression of myopia and axial eye length in children with esophoric fixation disparities.45 The same author published a case study on identical twins with myopia and esophoria. Progression of myopia was found during 1 year of wearing single-vision lenses followed by 1 year of no progression when wearing a concentric bifocal.46 The identical twin wearing bifocals throughout showed no myopia progression during the first year and limited progression (−0.25D) during the second year. Both studies, however, need to be considered in the context that the first is a non–peer-reviewed conference abstract and the second is a twin subject case study.
The proposed mode of myopia-controlling action is that a near esophore will underaccommodate to overcome the fixation disparity and thus induce hyperopic defocus that has previously been discussed as a driver to axial eye growth. The Johnson & Johnson design lens used in these studies has a center distance design surrounded by alternating concentric zones of near and distance power, which are designed to create two planes of focus. In the case of underaccommodation, the near vision bands should focus the anterior of the two focal planes closer to the retina than would be the case without bifocal correction and thus improve the hyperopic defocus that would otherwise occur. Whether this type of bifocal design would create a myopia-controlling effect in the absence of esophoria or lag of accommodation has not been tested as it could influence relative retinal defocus, so this proposed mode of action remains speculative.
Walline et al.47 investigated center distance aspheric multifocals with +2.00D power add, worn for 2 years in myopic children, to report 50% reduction in progression of myopic refraction and 29% reduction in axial elongation compared with a single-vision CL-wearing control group. A further reported outcome from this research was that the myopia-controlling effect appeared consistent during the 2-year duration of the study. Aspheric surfaces alter the SA induced by the lens, which has a direct effect on the shape of the peripheral image focus when compared with a spherical surface lens design.48 In the case of center-distance multifocals, this is a theoretical positive shift in SA and myopic shift in peripheral refraction profile. In a 2-year study, the CL providing the most positive SA had the greatest effect on slowing axial eye elongation.49
Kang et al.50 provided clinical confirmation that center distance aspheric multifocal lenses induce relative peripheral myopia; however, Ticak and Walline51 instead reported no change in the peripheral refraction profile with the same multifocal lens design. Both used similar instruments and methodology to measure the peripheral refraction profile, although Ticak and Walline51 had a smaller cohort and so had a low statistical power, which they attributed as a possible reason for showing a lack of significant effect. Commercially available stock single-vision soft CLs that use aspheric surfaces have also been investigated for effect on relative peripheral refraction and found to provide different outcomes depending on lens design and back vertex power.52
The lack of consistency in measured peripheral refraction profiles across these aspheric lens design studies suggests that attributing a beneficial relative myopic shift in peripheral refraction cannot be assumed as the influential factor underlying the myopia-controlling effect reported, and additional influence such as an effect on accommodation also needs to be considered. Further research is needed in this area to improve the understanding of how multifocal CLs provide a myopia-controlling effect and, similar to OK lenses, the longevity of effect and whether there is a rebound effect on discontinuation.
A further consideration with multifocal soft CLs is their effect on visual performance caused by the varying refractive power across their optical surface. Bickle and Walline53 investigated this factor to find that subjective and objective visual performance was worse when wearing center distance multifocals with +3.00D and +4.00D power compared with single-vision lenses. They concluded that add powers in the extended range (above +2.50D add) to potentially maximize myopia control may not be visually tolerated by myopic children.
Contact Lens Designs Specific to Myopia Control
There are currently two soft CL designs specifically created with the purpose of controlling progression of myopia that have been reported in the literature.
Dual-Focus Design (MiSight)
Anstice and Phillips54 described a novel dual-focus center distance concentric design soft CL. The central optic diameter is 3.36 mm surrounded by concentric rings of alternating near and distance focus, with the near add power fixed at +2.00D. The width of each ring is calculated for all rings to remain approximately equal in surface area so as to maintain approximately equal balance between distance and near correction with varying pupil diameter. The premise is that the central distance optic will be used to drive accommodation for all fixation distances, with the concentric near bands then creating an image field that always focuses anterior to the retina.
The study by Anstice and Phillips54 adopted a crossover design where one eye wore the dual-focus design and the fellow eye wore a single-vision distance-corrected CL for a 10-month period at which point the eyes swapped lens designs for a further 10 months. The study outcomes revealed 30% or more reduction of myopia in the eye wearing the dual-focus CL relative to the fellow eye wearing the single-vision distance-corrected CL. Contrasting the detrimental influence on vision identified by Cheng et al.49 from inducing positive SA, Anstice and Phillips54 reported no significant difference in visual acuity and contrast sensitivity with the dual-focus lens-wearing eyes when compared with the single-vision distance lens–wearing eyes. Kollbaum et al.55 compared the dual-focus design and a concentric center near bifocal CL against habitual best-corrected spectacle vision to find no difference in visual performance between the dual-focus and the bifocal design. The authors did however find reduced visual quality and ghosting ratings for both designs when compared with habitual vision, with logMAR visual acuity decreased by approximately one line for the dual-focus design. Although these two studies are in contradiction, the potential for visual compromise needs to be taken into consideration and balanced against the benefits from potentially slowing the progression of myopia.
A potential problem with the theory behind this design that needs to be considered is whether instead of using the central distance portion of the lens to drive accommodation demand, the wearer’s visual system instead relies on the benefit of the near add power when focusing at near. This would cause the focusing plane from the distance power rings to fall behind the retina and provide the opposite effect to that intended. Anstice and Phillips54 tested for this possibility during the study and reported that this was not the case.
Peripheral Plus Powered Aspheric Design
Sankaridurg et al.56 investigated an aspheric soft CL specifically designed for myopia control. The design consists of a central optic to provide refractive correction surrounded by progressively increasing relative positive power to reach +1.00D difference from the optic at a 2-mm semichord and +2.00D at the edge of the peripheral treatment zone, with a 9-mm total treatment zone diameter. Chinese children wearing these lenses were followed for 1 year and compared with age-matched children wearing spectacles in a concurrently running study at the same institution. The myopia control soft CL wearers exhibited 34% less increase in myopia and 33% less increase in axial eye elongation than their spectacle-wearing counterparts. The authors concluded that reducing peripheral hyperopia with this specific soft CL design can alter central refractive development and reduce the rate of progression of myopia.
FUTURE DEVELOPMENTS FOR MYOPIA CONTROL CONTACT LENSES
Many contemporary CL designs are not currently or previously covered by patents, so researching patents cannot provide a clear view into the future of CL design, but it does offer some clarity to crystal ball gazing beyond pure speculation.
The majority of patents on myopia-controlling CLs describe a method for controlling peripheral refraction with variations between the patents on how this is achieved. Most suggest that the central optic needs to be optimized for clear distance vision, but there is variation on the diameter across which this should be created, with most patents offering a range rather than defining a set parameter. The variations between these patents appear in defining the peripheral refraction zones of the lens.
Novartis (Basel, Switzerland), which owns the Alcon brand, also has patents lodged for a peripheral refraction–controlling CL. Its patents differ by describing methodology for controlling the optical effect beyond the mid-peripheral zones of the lens described in other patents.57 The peripheral zone of the lens in current designs is used to stabilize lens fit rather than provide an optical effect. Altering the periphery to control the optical effect creates significant challenges that need to be overcome to allow optical variation while standardizing factors like sagittal depth so as to allow consistent fitting independent of the optical effect. The Novartis patents describe the methods by which this can be achieved.
CooperVision (Fairport, NY) currently manufactures the MiSight lens that was investigated by John Phillips. Extending on this work, the group has published a patent that recognizes the optical limitations of this approach and defines a method whereby multiple sets of CLs are required to provide differing degrees of change to the peripheral refraction profile.58 The idea being that the lens profile is altered until the optimal balance between visual quality and myopia-controlling effect is achieved. A patent offering a similar multilens set approach has also been published by Novartis and Brien Holden Vision Institute (Sydney, Australia).59
The patent published by Bjorn Drobe with Essilor International (Charenton-le-pont, France) listed as the applicant similarly describes that multiple options are needed, except that, in this case, they describe a method of selecting the myopia-controlling intervention based on the animal work by Zhu et al.,60 which demonstrated changes to ocular biometry within as little as 10 min of exposure to a myopia-promoting stimulus.61 Drobe’s patent describes a device that induces a myopia-promoting stimulus for a short duration and then measures the effect on ocular biometry. Through repeating this process while using a variety of myopia-controlling devices, the patent holders claim that it will be possible to establish and prescribe the most effective prescription of treatment for that individual.
A novel addition to correction of peripheral refraction that has been published as a patent includes using the CL as an antimuscarinic agent delivery device.62 Atropine63 and pirenzepine64 have been shown to be effective in slowing the progression of myopia, with pirenzepine having less unwanted effects on mydriasis and cycloplegia but not commercially available. A concerning rebound effect on cessation of atropine treatment has been determined.43 Lowering the dose of atropine to 0.01% seems to provide comparable efficacy in controlling the progression of myopic refractive error,65 with less rebound effect on the cessation of treatment.66 The idea introduced by the patent is to allow sustained delivery of an antimuscarinic agent like atropine or pirenzepine to complement the myopia-controlling properties of the peripheral refraction–altering profile also included in the lens design. The potential here being that the two effects would be additive, leading to a greater myopia-controlling effect, although this has yet to be shown to be the case.
A novel use of OK to slow the progression of myopia that has been described under patent is a method to measure the peripheral refraction profile before lens wear and then using this information to calculate the shape of the OK lens that would induce the optimal corneal profile to induce a specified change to the peripheral refraction profile.67 This sounds promising in theory except that it has been shown that altering OK lens parameters seems to have little influence on the peripheral refraction profile, making attempts to customize peripheral refraction profiles a difficult task.68
Use of a pharmaceutical agent to fix the OK effect and prevent the need for continued overnight wear has been described,69 as well as a method to measure the optical effects induced from OK lens wear and from this design a soft CL that provides the same optical effect, thus replicating the beneficial myopia-controlling refraction profile induced by OK but in a more accepted soft lens modality.70
THE IDEAL MYOPIA-CONTROLLING CONTACT LENS
Based on the literature available to date, the ideal myopia-controlling CL needs to target the following properties:
- Induce peripheral myopia without compromising vision
- Reduce lag of accommodation
- Reduce near esophoria
- Provide controlled release of antimuscarinic agents
- Provide a beneficial shift in positive SA to improve near point depth of focus without compromising image quality
- Measure ocular biometrics and analyze surroundings to provide real-time advice and training in avoiding visual situations or environments that increase the risk of myopia progression.
Research knowledge is at the point of being aware of possible mechanisms of myopia progression; however, there is little if any understanding on which mechanisms are most influential on myopia development and what variability exists between different individuals. This suggests that, initially, the most successful designs will be those that target the most mechanisms in one product, such as providing a refractive alongside a pharmaceutical effect. In time, increases in knowledge should enable testing to identify what mechanisms are driving myopia development in an individual, so that a targeted rather than blanket approach to CL treatment can be taken.
In terms of revolutionary future CL applications for myopia control, it could be speculated that, with sufficient technological breakthroughs, CLs also offer the possibility to monitor various ocular factors that are influential to myopia development. For example, the exact dose of atropine could be released by the CL in response to measurements of pupil size also made by the CL so as to maintain the optimum balance for the peripheral refraction profile that is being provided by the same lens. It has been demonstrated in chickens that 10 min of myopia-inducing refractive stimulus is sufficient to alter ocular biometrics.60 A CL that has the ability to measure these ocular biometrics and communicate them in real time offers the possibility of a visual habit training solution by providing the wearer with feedback on visual situations that they should actively avoid or alternatively alert them when it is detected that they have spent too long fixed in close focus.
BARRIERS TO OVERCOME FOR CONTACT LENS CONTROL OF MYOPIA TO BECOME ACCEPTED
U.S. Food and Drug Administration Approval
A theoretical design will have more likelihood of achieving widespread acceptance with U.S. Food and Drug Administration (FDA) approval. Although not a requirement for acceptance outside of the United States, FDA approval provides a globally recognized indication that a high level of product efficacy and safety testing has been completed. A problem with FDA approval is the time and cost required and whether potential financial gains from the product are sufficient to significantly offset these costs. Currently, there are no CL products that have been approved by the FDA for use in myopia control, meaning that any practitioner promoting CLs to control the progression of myopia is doing so off-label.
Barriers Beyond FDA Approval
An FDA approval would help improve practitioner acceptance of a myopia control in the United States and the likelihood of using a myopia-controlling device; however, outside the United States, there are considerable other barriers that also need to be overcome—the most substantial of these being product availability.
Product Supply and Availability
It is apparent from the research to date that has been presented in this review that OK and specifically designed CLs can be used to slow the progression of myopia; however, none of these completely stops the progression of myopia and there remains a question on the duration of their effectiveness and within what period they need to continue to be worn to retain their effect. A number of studies also identified variability in effect, with some achieving greater than average effect seen in the test cohort, whereas in others, myopia progressed at the same rate as the controls.
The patents described above elude to this and suggest that individual characteristics beyond refraction and corneal shape will need to be taken into consideration to improve the myopia-controlling effect and to achieve this effect in more people. The CL market is now dominated by disposable soft lenses,71 which, through extensive development and various technological improvements, have generally reduced to a one-size-fits-all methodology. This removes all but one variable from the equation, leaving just refractive error and, consequently, production can be reduced to the number of refraction parameters required to correct the majority of potential end users. Adding back in the problem of providing a range of different peripheral profiles for each back vertex power naturally increases the number of lenses that would need to be produced and stocked and consequently introduces a considerable cost of manufacturing problem that will need to be balanced.
The problem of supply becomes even greater when international logistics are taken into consideration. For a number of reasons, the supply of existing soft disposable CLs in many Asian countries is limited. Their high populations and prevalence of myopia suggest that these markets would already be of interest to these companies just to supply standard myopia-correcting lenses. It must therefore be deduced that a number of barriers to supply are in place and will need to be overcome to allow distribution of a myopia-controlling CL to these populations that the research suggests are most at risk of myopia development and progression.
In an epidemiological study of ulcerative keratitis in Northern California, the incidence of corneal ulceration in CL wearers was 13 per 10,000 years compared with 1.4 per 10,000 years in non-CL wearers.72 This is slightly higher than that reported in an Australian population, with 1.9 cases per 10,000 years reported for daily wear of soft CLs and 11.9 per 10,000 years for daily wear of silicone hydrogel lenses.73 The incidence of microbial keratitis increases with overnight wear to 19.5 per 10,000 years and 25.4 per 10,000 years for overnight wear of soft and silicone hydrogel lenses, respectively. Loss of vision was found to occur in 0.6 per 10,000 wearers. The incidence of microbial keratitis in OK is estimated as 7.7 per 10,000 years overall and 13.9 per 10,000 years in children.74
The clinical conundrum here is that there is perhaps a greater risk to loss of sight through not considering a myopia-controlling intervention. Atrophic maculopathy/retinopathy is the most common sight-threatening pathology associated with high levels of myopia.75 Vongphanit et al.76 investigated data from the Sydney Blue Mountains Eye Study to reveal 0.42% prevalence of myopic maculopathy in myopes of less than 5D, which increased 60-fold to 23.5% in those with greater than 5D of myopia. The risk of retinal detachment77 and glaucoma6 also increases with higher degrees of myopia. Putting this research into context, keeping a −1.00D myope from reaching −3.00D reduces risk odds by four to five times for myopic maculopathy, three times for retinal detachment, and one and a half times for posterior subcapsular cataract.78 Brennan79 brought this into further perspective by analyzing frequency distribution data to model the impact of various degrees of myopia control. He establishes that reducing the progression of myopia by 33% would result in a 73% reduction in frequency of myopia higher than 5.00D and that there would be 90% less high myopes if progression was arrested by 50%.
These levels of myopia control are achievable with current multifocal myopia control–specific and OK CLs, so beyond the constraints already discussed, such as needing to be provided off-label, it would seem that the case for offering CLs for myopia control outweighs the risk of allowing myopia to develop unabated.80 Furthermore, it makes the case that time is of the essence, with continued development of myopia-controlling strategies needed to slow a seemingly growing future major public health problem.
Specific multifocal contact lens designs and OK have been shown to be effective in slowing the progression of myopia to a limited effect, at least in the short-term, with further research required to establish the length of effect and stability of effect once wear is ceased. This review of the literature and published patents has identified mechanisms for myopia development that are being targeted by currently available CL designs and areas of development with new designs. Whether these future CL designs will improve the efficacy of myopia control remains to be seen.
Through discussing barriers to uptake of myopia-controlling CLs, it has been identified that there is a need for recognized acceptance such as FDA approval for myopia control to develop beyond off-label use. There are also considerable international supply issues to overcome for myopia-controlling CL to reach populations that are impacted the most by what has been described as a myopia epidemic.
With high myopes more prone to sight-threatening disease, time is also an issue. It has been suggested that slowing myopia by just 33% would result in 73% reduction in frequency of myopia higher than −5.00D and consequent reduction in the severity of myopic pathology. Published studies have shown that this is within the realm of existing multifocal designs and OK, yet despite this evidence, myopia control is yet to establish a foothold in general optometric practice.
There is evidence in the patent literature that significant development work is underway and indications that, as the etiology of myopia becomes more greatly understood, there will be a CL that can be used to more accurately and individually target slowing the progression of myopia and arrest the otherwise growing future burden of sight-threatening pathology.
School of Optometry and Vision Science
University of New South Wales
New South Wales, 2052
Received April 7, 2015; accepted June 4, 2015.
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