|Ahead of print publication
Peripheral defocus as it relates to myopia progression: A mini-review
Nir Erdinest1, Naomi London2, Itay Lavy3, David Berkow4, David Landau3, Nadav Levinger5, Yair Morad6
1 Department of Opthalmology, Hadassah-Hebrew University Medical Center, Jerusalem; The Myopia Center, Rishon LeZion, Israel
2 Naomi Vision Boutique, Jerusalem, Israel
3 Department of Opthalmology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel
4 Optometry and Vision Science, Aston University, Birmingham, UK
5 Department of Opthalmology, Hadassah-Hebrew University Medical Center, Jerusalem; Department of Ophthalmology, Assaf Harofeh Medical Center, Zerifin, Israel
6 The Myopia Center, Rishon LeZion; Department of Opthalmology, Enaim Refractive Surgery Center, Jerusalem, Israel
|Date of Submission||11-Aug-2022|
|Date of Acceptance||12-Sep-2022|
|Date of Web Publication||11-Jan-2023|
5 Even Israel, Jerusalem
Source of Support: None, Conflict of Interest: None
Myopia is the most common refractive error in the world and has reached a pandemic level. The potential complications of progressive myopia have inspired researchers to attempt to understand the sources of myopia and axial elongation and to develop modalities to arrest progression. Considerable attention has been given over the past few years to the myopia risk factor known as hyperopic peripheral blur, which is the focus of this review. It will discuss the primary theories believed to be the cause of myopia and the parameters considered to contribute to and influence the effect of peripheral blur, such as the surface retinal area of blur or the depth of blur. The multitude of optical devices designed to provide peripheral myopic defocus will be mentioned, including bifocal and progressive addition ophthalmic lenses, peripheral defocus single-vision ophthalmic lenses, orthokeratology lenses, and bifocal or multifocal center distance soft lenses, as well as their effectivity as discussed in the literature to date.
Keywords: Hyperopic peripheral blur, myopia, peripheral defocus
|How to cite this URL:|
Erdinest N, London N, Lavy I, Berkow D, Landau D, Levinger N, Morad Y. Peripheral defocus as it relates to myopia progression: A mini-review. Taiwan J Ophthalmol [Epub ahead of print] [cited 2023 Jan 28]. Available from: https://www.e-tjo.org/preprintarticle.asp?id=367588
| Relative Peripheral Defocus and Myopia Progression|| |
Myopia is the most common refractive error worldwide, and its growing frequency is considered an epidemic spanning the entire literate world., Left untreated, progressive myopia can lead to severe complications affecting vision, ocular alignment, and even blindness.,, Genetic and environmental factors influence myopia occurrence and progression; some seem closely linked.,,
From the genetic perspective, genome and candidate gene-based association studies have identified over 600 refraction and myopia-linked loci. However, these genes' specific roles and clinical manifestations are not yet understood. These genes often have multiple functions and have been discovered to be involved in synaptic transmission, cell–cell adhesions, calcium ion binding, cation channel activity, and plasma membrane function.
Some genes are light dependent, which may affect the cell cycle and growth pathways. Therefore, lack of outdoor activity and higher levels of education, which may be related, are probably other important factors., Animal models suggest that exposure to sunlight stimulates retinal dopaminergic pathways, which then interfere with eye growth signaling pathways, thereby preventing excessive elongation.
Excessive and prolonged accommodation associated with near work is also a possible catalyst for axial elongation by releasing chemical mediators which induce scleral and retinal growth. Hyperopic peripheral blur is a known risk factor for myopia development, while myopic peripheral blur in the retina may arrest this progression, [Figure 1]. In recent years, searching for a treatment that will arrest myopia progression yielded several treatment options. Besides recommending diluted atropine, orthokeratology, bifocal or progressive addition ophthalmic lenses, soft multifocal center-near-peripheral-blur contact lenses have also been effective.
|Figure 1: Myopic correction with single-vision contact lenses or single-vision spectacles equally corrects myopia at the fovea and the peripheral retina. The myopic eye's fovea and peripheral retina are in different myopic states. The peripheral retina is more hyperopic; therefore, equal correction, peripherally and central, is likely to enhance myopia progression (a). As illustrated, myopic correction with peripheral defocus contact lenses or spectacle lenses correct the degree of myopia at the fovea but creates myopic defocus in the peripheral retina by providing additional positive power in the periphery, thus retarding myopia progression (b)|
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This article will discuss peripheral defocus as it pertains to myopia and the optical alternatives devised in an attempt to control its progression.
| Search Strategy|| |
In this article, a thorough search was conducted in the professional literature in the Medline (National Library of Medicine, Bethesda, Maryland, USA), Scopus (Elsevier Inc., Amsterdam, The Netherlands), and Thomson Reuters Web of Science databases and search engines.
The search included terms such as "Peripheral Defocus," "Peripheral Hyperopic Defocus," or "Relative Peripheral Refraction, as well as the words "Myopia," "Myopia Progression," and "Myopia Control."
The search yielded 137 peer-reviewed articles, and from the references of those articles, another 17 articles related directly to relative peripheral refraction and myopia progression were identified.
| Theories of Relative Peripheral Defocus and Myopia Progression|| |
The influence of peripheral defocus on eye growth manifested in animal studies has encouraged researchers to explore optical corrections for humans to control myopia progression. Smith 3rd et al. ablated the foveae of 13 rhesus monkeys with photocoagulation to demonstrate the peripheral retina's role in emmetropization. The refractive state was then monitored using retinoscopy, keratometry, and A-scan ultrasonography, and there were changes noted in the refractive state even following foveal ablation.
The importance of the peripheral retina has been exhibited in studies whereby controlling the retinal defocus can modify the growth and refractive state of the eye. Specifically, creating peripheral hyperopic defocus can cause axial myopia, whereas peripheral myopic defocus can lead to axial hyperopia.,, Researchers have found that the baseline peripheral refraction in isolation does not predict the onset or progression of myopia.,, The development of myopia associated with the change from relative peripheral myopia to relative peripheral hyperopia was apparent in a study by Snq et al. on children in Singapore.
There are two primary theories regarding the physiological progression of myopia. One theory hypothesizes that hyperopic retinal blur caused by a high lag of accommodation during near work accelerates axial elongation.,, The second theory suggests that mechanical tension created by the crystalline lens or ciliary body restricts equatorial ocular expansion, causing accelerated axial elongation.
Work from animal models suggests that form deprivation and retinal defocus initiate a signaling cascade that leads to several cellular and biochemical changes in the retina and the retinal pigment epithelium.,,, These chemical signals are transmitted through the choroid, causing changes in scleral extracellular matrix (ECM) synthesis, which alters the biomechanical properties of the sclera, leading to increases in ocular growth and a more myopic refractive state., Animal studies and models have shown that the choroid plays an active role in emmetropization via modulation of its thickness to adjust the retina to the focal plane of the eye (choroidal accommodation) through the release of growth factors that have the potential to regulate scleral ECM remodeling., Experimental studies have identified that several biochemical compounds, such as retinal dopamine, retinoic acid, and nitric oxide, are involved in modulating axial length (AL) changes.,,
Possible mechanisms driving axial growth include high levels of retinal blur caused by axial aberrations, form deprivation resulting from poor retinal image quality in distance vision, enhanced accommodative lags over time encouraging compensatory eye growth, and an absence of adequate cues to guide emmetropization.,
While foveal defocus has been discussed as a promoter of myopia, which is part of the incentive to prescribe lenses with an addition for near work, the peripheral blur threshold that propels eye growth seems to be a more significant influence.
A concept of local control has been discussed: manipulating the visual environment in one area of the visual field and influencing only the refractive state in the corresponding retinal area. This concept could raise an argument against peripheral defocus affecting refractive error at another location, such as the fovea, the standard location where measurement of myopia as well as AL (at the retinal pole) is performed and determined as the communicated measure for progression or lack thereof. Generally, myopic eyes have relative peripheral hyperopic defocus in the horizontal meridian, indicating that it may be a potential growth signal; however, most research measurements are taken only at the horizontal and, infrequently, the vertical meridian. A study measured the peripheral refractive error in five meridians of patients' peripheral retinas (up to 40° from the fovea). It concluded that asymmetric profiles, especially when skewed temporally or nasally, seemed to be influenced less by defocus multifocal contact lenses than those with symmetric profiles.,, This concurs with a study that found asymmetric peripheral refraction patients were less prone to myopia progression, indicating that they may be less receptive to changes that induce myopia, such as peripheral defocus.,
A previous study by Mutti et al. noted that in the 2–4 years before myopia onset, there was an increased rate of change toward a negative refractive error, increased AL, and a more hyperopic relative peripheral refractive error (measured at 30° from the fovea). These multiple presentations may assist in predicting the onset of myopia.
| Peripheral Refraction–location and Degree|| |
The sensitivity to blur decreases as the distance from the forvea increases, which suggests that more peripherally, greater magnitudes of defocus may be required to result in a detectable blur. Others contend that just as with accommodation, capable of being stimulated at much lower levels than the depth of focus (DOF), the amounts of peripheral defocus may not need to exceed the DOF to trigger the myopia progression. In addition, blur sensitivity usually describes the ability to perceive the focus of the image, which requires neural processing. Unestablished is what level of blur is optimal to influence eye growth. The feedback loop for emmetropization seems to occur entirely at the retina level, perhaps due to a specific type of ganglion cells.,
While it is unclear what level of defocus and at what retinal eccentricity might influence foveal refraction, most studies successfully influence eye growth when targeting the area between 20–40 degrees from the visual axis. The percentage of surface area required to affect myopia progression has not yet been determined.,
It is important to recognize that regardless of the lens type, one that corrects a higher amount of central myopia results in a more hyperopic peripheral shift than a lower-powered lens of the same type. Therefore, a higher degree of myopia potentially influences the continuation of growth more than a lower refractive correcting lens. As mentioned, undetermined is the degree of blur required to influence this hyperopia or the refractive status of the periphery (emmetropic, myopic, and to what degree), and, therefore, the amount of addition required in the periphery is also under consideration. So still unestablished is the necessary depth of defocus, how much retinal area of blur is needed to be effective, and whether an image can be too blurry to be effective.
| Optical Devices that Provide Peripheral Defocus and Their Effectivity|| |
Conventional single-vision ophthalmic lenses used to correct myopia have been shown to increase hyperopic defocus at the retina's periphery. As the amount of myopia corrected increases, so does the magnitude of the peripheral hyperopic defocus.
| Bifocal Ophthalmic Lenses|| |
One of the earliest optical solutions used in an attempt to arrest myopia progression is the bifocal lens. In addition to addressing accommodative lag and binocular imbalances, a bifocal lens provides sectorial peripheral defocus in the superior retina. Walline et al. conducted a review on myopia control where they found that both bifocal and multifocal ophthalmic lenses have some effect on controlling myopia but not enough, in their view, to recommend using this modality, even for those with a high accommodative lag and near-point esophoria. The increased positive power for near has a negative effect on the oculomotor balance in children with orthophoria, reducing myopia progression's effectiveness., However, a trial using a prismatic bifocal lens showed a more significant effect among children with low lags of accommodation due to reduced convergence and lens-induced exophoria with prismatic correction., In the case of the children with a low accommodation lag, the AL change over 3 years for those wearing the prismatic bifocal was 0.46 mm. In contrast, in those wearing the standard bifocal, the change in AL was 0.6 mm over the same time period.
| Progressive Ophthalmic Lenses|| |
A study comparing myopia progression between single-vision (SV) spectacles and children wearing progressive addition lenses (PALs) reported that those with superior myopic defocus (PALs) had significantly less central myopia progression than those with superior hyperopic defocus (SV). Expectedly, PALs resulted in a large myopic shift in the superior retina, but the change at the other peripheral locations, though present, was smaller. Studies compared the use of PALs with SV lenses and showed a small, statistically significant, but clinically insignificant change in myopia progression between them of 0.20D over 3 years.,,,
Myopia control studies have observed that in some instances, the children wearing PALs failed to use the near reading zone for near viewing. Findings of sectorial defocus influencing sectorial AL inspired researchers to develop optical solutions that would provide equal defocus over the entire retinal circumference.
| Peripheral Defocus Ophthalmic Lenses|| |
One must remember that an ophthalmic lens with peripheral defocus is limited, as its effect is altered in primary versus other gaze directions. These designs are relatively new and still being studied [Table 1].
|Table 1: Commercially available peripheral defocus design ophthalmic lenses|
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An SV lens called the Defocus Incorporated Multiple Segments (DIMS), developed at Hong Kong Polytechnic University and manufactured by HOYA, comprises a central optical zone of 9 mm in diameter for correcting refractive error at distance and annular multiple focal zones with multiple segments of 33mm in diameter which have a relatively positive power of +3.50D., The diameter of each of these segments is 1.03mm. In a 2-year study, children wearing these lenses had an increase in myopia of −0.3D, whereas those wearing SV lenses had an increase of myopia of −0.93D. The increase in axial was 0.21 mm and 0.53 mm, respectively. In this study, the strongest effect was observed during the first 6 months of lens wear, apparently due to the higher myopia progression in the SV group during this time.,
A PAL named the Apollo lens (Apollo Eyewear, River Grove, IL, USA) comprises an asymmetrical myopic defocus design with a three-stage myopic defocus zone. These zones include a+2.50D full positive power superior zone, an 80% full myopic defocus power nasal zone, and a 60% full myopic defocus power temporal zone.,
In one study, perifocal ophthalmic lenses were assigned to children 7–14 years old with progressive myopia from −1.00 to− 6.00D. Perifocal ophthalmic lenses allow differentiating correction of the central and peripheral refraction of the eye along the horizontal meridian, thus correcting or reducing the peripheral hyperopia. In the 15° zone, 100% of the eyes formed myopic defocus, which averaged −0.05 ± 0.1D in temporal 15°, −0.25 ± 0.16D in nasal 15°, and −0.44 ± 0.03D in temporal 30°. In the nasal 30° zone, the hypermetropic defocus decreased by four times and amounted to 0.38 ± 0.03D. The rate of progression of myopia decreased from 0.80D of baseline values to 0.17D at 4–5 years of follow-up.
Essilor's (Charenton-le-Pont, France) contribution to the myopia control ophthalmic lens modality is the Myopilux series which includes a short corridor progressive addition of + 2D and incorporates a 3 base-in prism with a very wide reading zone, tailored to children with an exophoric posture. This lens is based on research done by Cheng et al., 2008. One variation has an executive design with an addition of +1.50D and 3 base-in prism each eye (6 base-in prism total).
Recently, Essilor introduced the Stellest lens, which incorporates a central SV center and eleven aspheric lenslets radiating outward. The power rings create signals in front of the retina, slowing eye elongation. It is designed using Highly Aspherical Lenslet Target Technology. This lens has the following configuration: 11 concentric rings of aspheric lenslets centered on a 9-mm diameter clear zone. Instead of using defocus lenses that focus light on two distinct surfaces, these aspherical lenses deviate rays of light continuously, creating a three-dimensional quantity of light in front of the retina. This is called the volume of myopic defocus. After a 1-year study including 170 myopic children, the results were as follows: in the treatment group, myopia progressed by −0.27D versus −0.48D among those wearing SV spectacle lenses (SVLs), whereas the AL change over the same period was 0.13 mm in the treatment group versus 0.36 mm on the SVL group.
Both lenses are based on the peripheral retinal defocus theory and have an effectivity of about 60%. The distinction is the technology used.
| Spherical Single-vision Soft Contact Lenses Compared to Single-vision Glasses|| |
The difference between peripheral refraction in ophthalmic lenses and spherical soft lenses (SCLs) has been investigated. All ophthalmic lens wear presents peripheral hyperopic defocus, which increases with refractive error. While one study found a myopic defocus (when prescribing for full refractive error) during SCL wear, most found hyperopic defocus with both correction modalities, whether under-corrected, on-refraction, or over-corrected. Walline et al. examined 247 soft contact lens wearers and 237 spectacle wearers aged between 8 to 11 and discovered that soft contact lenses did not significantly affect corneal curvature or axial elongation in this cohort compared to the spectacle wearers.
| Orthokeratology|| |
These corneal reshaping lenses are worn at night while sleeping. They flatten the central cornea while steepening the mid-peripheral cornea, primarily involving the epithelial layer. This reduces the relative peripheral hyperopia, which, in turn, seems to slow axial elongation. In one study, children wearing orthokeratology lenses over 2 years demonstrated an increase in AL and vitreous chamber depth of an average of 0.14 mm/year compared to an average growth of 0.27 mm in children that did not wear these lenses. Most research has shown the overall decrease in myopia control to be around 50%,,, a significant impact that can be linked to the peripheral defocus effect.,, The selection of orthokeratology lenses globally is flourishing, along with the ability to customize these lenses to change the area and placement of the peripheral blur and to accommodate the specific needs of patients to achieve success with higher and more complex prescriptions and topography.
| Bifocal and Multifocal Soft Contact Lenses|| |
Short-term studies on animals and children have reported that soft bifocal contact lens designs can slow myopia progression. To date, peripheral defocus contact lenses have been shown to be superior to peripheral defocus ophthalmic lenses, but studies are being conducted on newer technologies that may reveal new data., The combined potential benefit of peripheral defocus contact lenses may affect myopic progression because of the additional bifocal effect on accommodation has been reported and investigations to substantiate this continues.,, Both concentric ring bifocals and peripheral addition multifocal soft contact lenses have been shown to be clinically effective for decreasing myopia progression in school-aged children, with an overall myopia control rate of 30%–50% over 2 years. Concentric ring bifocal soft contact lenses seem to have a greater effect than peripheral addition multifocal soft contact lenses. The BLINK Study showed that 51% of the participants progressed more than −1.00D over a 3-year period compared to those wearing +1.50D addition and +2.50D addition multifocal contact lenses who progressed <−0.85D and −0.56D, respectively. Overall, the effect of bifocal soft contact lenses on myopia control in the literature varies, ranging from 25% to over 70% reduction in myopia progression. Some of these studies report results after only 1 year. The more variable results have been observed with soft bifocal contact lenses in comparison to orthokeratology, which may be due, among other reasons, to differences in lens design, compliance with wearing the contact lenses, or the number of hours of wear.
| Contact Lenses Designed to Manage Myopia|| |
Various soft lenses with simultaneous vision designs that provide peripheral retinal defocus are available [Table 2].
|Table 2: Commercially available contact lenses with a peripheral defocus design|
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| Dual-focus Design|| |
Commercially known as MiSight (CooperVision, USA), these lenses have a central zone with a diameter of 3.36 mm that corrects the refractive error and concentric treatment zones that create 2.00D of simultaneous myopic retinal defocus during distance and near viewing. The defocus is comprised of two alternating treatments and two refraction correcting zones causing peripheral defocus on the retina, creating dual-focus viewing. The trial conducted by Anstice and Philips showed that eyes wearing these contact lenses had significantly less axial elongation than eyes wearing SV lenses. Following the above study, Chamberlain et al. conducted a multicenter study in several countries over 3 years. The refractive error progression in the first year was 0.40D less compared to the control group. In the second year, the progression was 0.54D less, and in the third year, 0.73D less than the control group. The axial elongation change was as follows: at 12 months, the AL change in the control group was 0.24 mm compared to 0.09 mm in the MiSight group. At 24 and 36 months, the AL change was 0.24 and 0.32 mm less than the control group, respectively. In terms of refraction , the myopia control effect after 3 years was 59%, and in terms of AL control, the effect was a 52% decrease.
| Extended Depth of Focus Contact Lens|| |
The extended depth of focus lenses used in a study is commercially named Mylo (Mark'ennovy, Spain). Two options of extended focus depths are available, including higher-order aberrations equivalent to additions of + 1.75D (lens #3 in the study) and + 2.50D (lens #4). When examined after 2 years, the lenses slowed myopia progression by 32% and 26%, respectively.
| Multifocal with High Peripheral Blur|| |
The NaturalVue Multifocal 1 Day Contact Lens (Visioneering Technologies, USA) is designed to provide approximately 8.00–11.00D of relative plus power at the edge of the pupil and approximately 20.00D of relative plus power at the edge of the optic zone. This is the largest degree of peripheral plus power commercially available in a center-distance multifocal contact lens. This lens has exhibited high potential for halting myopia progression in a multicenter case series analysis of 32 patients. Approximately 98% showed a decrease in annual myopia progression, 91% a 70% decrease or more, and a few patients exhibited myopia regression.
| Future Studies|| |
Future studies will need to clarify several queries, for example, which visual regions apart from the fovea are most impactful in controlling myopia, and how age of treatment may impact influence.
Researchers are exploring the option of influencing AL growth monocularly in cases of anisometropia.
A study comparing efficacy between the DIMS SV lens and the Apollo progressive addition lens began in October 2019 and is still underway.
"SightGlass Vision (Palo Alto, CA, USA)", a clinical-stage research and development company, is conducting a three-arm trial comparing a novel single-vision ophthalmic lens design versus single-vision spectacles.,
The Personalized Addition Lenses Clinical Trial study compares a customized addition progressive add ophthalmic lens to standard +2.00D addition progressive added lenses and SV lenses.
Work published by Mutti et al. concluded that the relatively slower rate of change after myopia onset in myopia progression, axial elongation, and peripheral hyperopia suggests multiple factors that may influence myopia progression. Studies have begun to explore the potential of combination therapies for myopia control, where perhaps each peripheral defocus modality has minimal to moderate benefit, but the combination with another effective therapy, such as low-dose atropine, has enhanced effectivity.,,
In summary, myopia progression is a complex condition where multiple factors must be considered as they influence each other. This article focused on the peripheral blur signal on the retina. While peripheral myopic defocus has proven to be a potent trigger for halting myopia, the amount of defocus necessary to have a meaningful effect is unclear. One possibility is that a dose–response relationship exists, meaning more significant amounts of defocus result in greater reductions in myopia progression, unknown to what degree. Another possibility is that any amount of myopic peripheral defocus above some threshold acts as a signal to slow myopia progression and the location is important. Alternatively, or in combination, perhaps more significant reductions in myopia progression are possible as more peripheral locations experience myopic defocus.
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Conflicts of interest
The authors declare that there are no conflicts of interests of this paper.
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[Table 1], [Table 2]