Does peripheral retinal input explain the promising myopia control effects of corneal reshaping therapy (CRT or ortho-K) & multifocal soft contact lenses?

Authors


  • *All authors contributed equally to this paper.

Abstract

In the following point-counterpoint article, internationally-acclaimed myopia researchers were challenged to defend the two opposing sides of the topic defined by the title; their contributions, which appear in the order Point followed by Counterpoint, were peer-reviewed by both the editorial team and an external reviewer. Independently of the invited authors, the named member of the editorial team provided an Introduction and Summary, both of which were reviewed by the other members of the editorial team. By their nature, views expressed in each section of the Point-Counterpoint article are those of the author concerned and may not reflect the views of all of the authors.

Concern over the rapid rise in myopia prevalence world-wide is reflected in experimentation, both within the laboratory and within the clinic, with treatments that may slow or arrest myopia. The serendipitous clinical observations of clinically significant slowing of myopia progression with some concentric multifocal soft contact lenses, already approved as presbyopia corrections, and corneal reshaping therapy (CRT or orthokeratology, ortho-K), designed to obviate the need for myopes to wear day-time optical corrections, refocused attention on the results of early, much cited Hoogerheide et al. studies apparently linking off-axis hyperopia with an increased risk of myopia. Could such off-axis refractive errors underlie myopia? After all, there is robust evidence from animal model studies that uncorrected hyperopia, e.g., imposed with defocusing lenses, accelerates eye growth in young animals. That myopic human eyes are typically prolate in shape is also not under debate, nor is the fact that traditional single vision spectacle corrections will exaggerate any off-axis hyperopia. Do the therapeutic effects of CRT and multifocal contact lenses reflect the correction of these off-axis errors? And is the more limited benefit of multifocal spectacles lenses, prescribed for myopia control, due to the fact that their correction of off-axis hyperopia is limited to one quadrant? Or are there other explanations? Answers to these questions have very real implications for refinement of existing contact lens designs for myopia control and defining the scope of additional innovative optical treatments.

Point

It is firmly established that optical treatment strategies can slow myopia progression in children. The central issue considered in this point article is whether the effectiveness of optical interventions can be increased by expanding the extent of visual field manipulated. In this respect, the evidence is very strong and very positive. First, animal research, much of it pioneered by Josh Wallman, has provided a strong theoretical foundation for peripheral optical treatment strategies. In particular, animal research has demonstrated that visual signals from the fovea are not essential for vision-dependent ocular growth. The periphery, in isolation, can mediate normal refractive development, and when there are conflicting visual signals between the fovea and the periphery, peripheral visual signals can, probably as a result of areal summation,[1] dominate central refractive development.[2] Moreover, animal studies have shown that imposing myopic defocus in the periphery can slow axial growth and produce central hyperopic shifts in refractive error.[3] These observations are critical to human treatment strategies because the operating characteristics of the vision-dependent mechanisms that regulate refractive development are very similar across a diverse range of animal species and when comparable viewing conditions are established in animals and humans, the effects on refractive development have been shown to be qualitatively similar.

The emerging pattern of results from myopia control studies support the hypothesis that treatment strategies that take into account the optical state of the periphery are more successful than those that do not. Figure 1 illustrates the relative reduction in myopia progression obtained from representative studies using different optical treatment regimens. Between studies comparisons emphasize that the extent of the treatment zone influences treatment efficacy. For example, the beneficial effects of progressive addition lenses (PALs) on myopia progression is correlated with the degree of peripheral myopic defocus produced by the add segment in a limited part of the superior retina.[4] In this respect, the greater reduction in myopia progression rates reported with executive bifocals can reasonably be attributed to the fact that the larger add segments in executive bifocal lenses impose relatively high degrees of myopic defocus over a much larger proportion of the visual field than PALs.[5, 6]

Figure 1.

Relative differences in myopia progression obtained in representative studies between control subjects, who wore either single-vision spectacles or contact lenses, and experimental subjects, who wore lenses designed to reduce myopia progression. Negative values indicate that myopia progression was lower in the treated subjects. The selected studies were chosen because the therapeutic effects found in each study were near the average for all studies using similar treatment strategies. PALs, progressive addition lenses;[6] E-type, executive bifocals;[5] BFCLs, simultaneous bifocal contact lenses;[8] CRT, corneal reshaping therapy or orthokeratology;[7] Peri-Specs, spectacle lenses that selectively decrease peripheral hyperopia;[9] Peri-CLs, contact lenses that selectively decrease peripheral hyperopia.[10]

In terms of influencing the eye's peripheral optical state, more aggressive optical treatment profiles can be created using contact lenses and corneal reshaping therapy (CRT). For example, with multifocal contact lenses, absolute myopic defocus is simultaneously imposed over the fovea and much of the peripheral retina. With CRT, the correction for the central manifest refraction is restricted to the central ±10° of the visual field. CRT's eccentricity-dependent increases in corneal power produce relative peripheral myopia in all meridians with the degree of peripheral myopia increasing with the magnitude of the central correction. As illustrated in Figure 1, the beneficial effects obtained with both of these strategies are larger than those obtained with PALs. In addition, the similarity of the results between CRT[7] and ‘dual-focus’ contact lenses[8] suggest that the overall contribution of visual signals from the fovea to slowing myopia progression is small. This similarity is in agreement with the observations that eliminating visual signals from the fovea does not significantly affect the degree of myopia produced by form deprivation or negative-lens-induced defocus in monkeys.[2] In this respect, the failure of traditional undercorrection strategies, which primarily affect foveal vision, demonstrates that concentrating optical treatment effects to the fovea is not sufficient to slow myopia progression.

Recent results obtained using spectacles[9] and contact lenses[10] that were specifically designed to reduce peripheral hyperopia also emphasize that the extent of the peripheral treatment zone is important. Sankaridurg et al.[9] examined three different experimental spectacle designs. In each case, lens power became more positive with eccentricity; however, the lenses differed in the extent of the peripheral field that was affected by the positive-powered portion of the lens. The two most conservative designs, which produced modest or no measurable effects on the degree of peripheral hyperopia in the central 80° of the retina, had no effect on myopia progression. The third design, which imposed relative positive power over a large part of the periphery and in many respects resembled an up-side-down PAL, produced a measurable reduction in myopia progression. However, as illustrated by the right two bars in Figure 1, the novel contact lens design, which produced relative peripheral myopia over much of the visual field, resulted in a greater reduction in myopia progression than the novel spectacle lens designs, plausibly because the optical treatment zones of the contact lenses affected a much larger part of the visual field than the peripheral treatment zones of the experimental spectacle lenses.

Although the role of peripheral hyperopia in the genesis of myopia in children is unresolved, the evidence from the laboratory research and the clinical studies summarized above indicates that optically imposed peripheral myopic defocus can slow myopia progression. There is no doubt that procedural and methodological differences between the available studies, some of which are preliminary in nature, could confound some of the comparisons noted above. However, in my view the available evidence clearly indicates that involving the peripheral retina increases beneficial treatment effects and is probably the primary reason for the promising results obtained recently using strategies that include optical treatment effects that encompass a large part of the peripheral retina. Another potentially important factor to consider is that strategies that selectively target the peripheral retina (e.g., CRT and contact lenses specifically designed to produce relative peripheral myopia) can have substantial therapeutic benefits against myopia progression while at the same time providing optimal central vision.

Counterpoint

The rapid rise in myopia prevalence worldwide brings urgency to halting the progression of myopia or reversing it. Over 12 months, progressive contact lenses (designed to correct relative peripheral hyperopia (RPH)), reduced myopia progression 34%[10] compared to single vision spectacles. Concentric bifocals compared to single vision contact lenses also reduced progression (30% over 20 months).[11] Correction with corneal reshaping therapy (CRT, which reduces RPH), reduced the rate of myopic progression up to 43% over 2 years.[7] In order to achieve larger treatment effects, including ultimately, the reversal of myopia, it is important to understand the underlying mechanism(s). While it may appear from these results that reduced RPH or peripheral myopic defocus reduces progression or that RPH causes myopia, evidence to the contrary exists.

Does RPH cause myopia?

In order for RPH to cause myopia, it must be detected by the visual system, be relatively constant and precede myopia onset. The amount of peripheral defocus only begins to differ from the axial error outside the central 10–30°[12] where cones and ganglion cells may not be dense enough to detect it. With spectacles, average RPH of <1D at 20°[13] in moderate myopes, is likely within the depth of field for most subjects[14] and thus undetectable. RPH is even less with lower myopia. Also, defocus from RPH is expected to vary with task[15] and accommodation.[12, 15] In addition, although myopic children demonstrate RPH in the horizontal meridian, they sometimes display relative peripheral myopia[16] in the vertical meridian. Recently, changes in eye shape and RPH have been shown to accompany rather than precede myopia onset.[12, 17, 18] Hoogerheide and coauthors' findings have been questioned because they (1) only studied late onset myopes,[12] and (2) may not have measured peripheral refraction prior to myopia onset. Overall, RPH was not a statistically significant risk factor for myopia[17, 18] and appears to have little influence on its progression.[17, 18]

Given that RPH accompanies central myopia progression, both could simply reflect a fixed retinal shape in the periphery combined with a smooth transition to the longer myopic eye centrally.[12] RPH could result from a stronger reaction to a myopigenic stimulus centrally than in the blurred periphery with its lower resolution.[12] Both might reflect a breakdown in the recognition of defocus blur, perhaps related to a reduction in blur sensitivity in myopes.[14] The optics of the eye are known to change in the presence of imposed defocus, at least in chicks, giving larger aberrations and astigmatism.[19, 20] These changes might also produce RPH as a secondary effect concurrent with myopia.

Is the correction of RPH (or the introduction of peripheral myopia) the source of the reduction in the myopia progression observed in contact lens trials?

There is evidence that CRT and bifocal contact lenses do not slow progression of central myopia via a correction of RPH or the introduction of peripheral myopia. When central correction was introduced with spectacle lenses designed to correct RPH, there was an insignificant effect on myopia progression.[9] Similarly, single vision spherical soft contact lenses providing partial correction, correction or overcorrection of RPH[13] did not reduce myopia progression.[21] In contrast, centre distance varifocal contact lenses, also designed to correct RPH, do reduce myopia progression,[10] likely because of their other simultaneous effects. With either CRT or bifocal contact lenses, simultaneously with the correction of RPH, signals to the direction of defocus such as peripheral astigmatism and axial spherical aberration, will be increased and a stop growth signal may be provided from the near (myopic) image,[16] halting progression. Alternatively, there may be a larger depth of field without a clear bifocal effect, possibly reducing signals which previously resulted in progression. These effects also offer a possible explanation for enhanced treatment effects observed with larger pupils.

Insights from studies of animal models

Studies of animal models give insights into mechanisms of novel contact lens corrections. However, differences from humans include: that lens-induced myopia in animal models is stable and that the retinal images produced by bifocal lenses will depend on the specific aberrations of that species. Most experiments with animal models are designed to produce emmetropization to defocus imposed by lenses rather than correction of existing defocus.

While lens corrections can induce RPH[22] and bifocal lenses can induce effects consistent with a response to RPH,[3] it does not follow that RPH is the cause. In monkeys, with and without an intact fovea, peripheral defocus appears to determine the central refraction.[2] Contrary to this, the retina exhibits a local response to peripheral defocus and form deprivation.[1] Foveal myopia, apparently induced by peripheral defocus, could result from smoothing of the deformed off-axis retina across the fovea rather than a peripheral override of the central response. Alternatively a weighted central field response to multiple, differentially-blurred targets is possible but over what visual angle is unclear.[23]

Central responses to myopic or plano defocus dominate in the presence of simultaneous hyperopic defocus.[24] When the center and peripheral fields are differentially blurred or deprived, a central retinal response can dominate.[25] Even when the lens induces RPH,[26] some bifocal lens results in chicks and primates are consistent with a central response close to the average power over the pupil.[3, 22, 24, 26]

During recovery from myopia, results from Liu and Wildsoet[22] suggest an advantage to bifocal lens designs, irrespective of differing RPH. Bifocal lenses can induce refractions that differ from those imposed centrally but are inconsistent with a strictly peripheral influence.[24] Some results[22] are consistent with increased depth of focus or spherical aberration reducing the signal to the direction of defocus centrally without producing form deprivation myopia.[27]

Conclusions

We summarized evidence indicating that myopia and its progression are not fully explained by peripheral effects and that explanations other than correction of RPH exist for encouraging results from myopia control trials. In order to understand the mechanisms of the promising effects of CRT, bifocal and multifocal contact lenses, further measurements across the visual field of both refraction and image quality are needed. Improved therapies with proven long term efficacy are still needed as these therapies cause a decrease in contrast sensitivity and may have other effects on children's vision.

Summary

Christine Wildsoet

Center for Eye Disease & DevelopmentSchool of Optometry, University of California, Berkeley, USA

E-mail: wildsoet@berkeley.edu

Points of Agreement

The role of peripheral hyperopia, i.e., hyperopic defocus on the retinal periphery, in myopia development is not resolved. Indeed, there are recent data arguing against its role in myopia progression.

In some myopes, a significant slowing of myopia progression is achievable with corneal reshaping (CRT) lenses as well as certain types of multifocal contact lenses. In general, these contact lens treatments show more promising outcomes than do those of spectacle lenses, even for the more novel designs such as the Peri-spectacles.

Neither of the contributors to this point-counterpoint article challenges the claim that myopia progression can be controlled optically. The question of underlying mechanisms needs to be addressed if the efficacy of these treatments is to be improved.

Points of Disagreement

The two main points of disagreement are (1) the extent to which results from animal studies supporting the local retinal regulation of eye growth can be generalized to humans, and (2) the extent to which contact lens-induced changes in the defocus experienced by the peripheral retina with CRT and dual focus lenses underlies the observed inhibitory effects.

Some of the arguments presented by Smith rest on the assumption that peripheral hyperopia underlies myopia progression, and Campbell and Irving rightfully point to evidence against this viewpoint and question the ability of the peripheral retina to detect the reportedly small degree of peripheral defocus. Campbell and Irving offer alternative possibilities.

By contrast, the arguments presented by Smith do not rely on the presence of relative peripheral hyperopia underlying myopia progression; rather, he points to relative peripheral myopia as the key to successful treatment, with the areal extent of peripheral retina exposed to such stimuli being another important variable.

Biographies

  • Image of creator

    Earl L. Smith III

  • Image of creator

    Melanie C. W. Campbell

  • Image of creator

    Elizabeth Irving

Ancillary