By Eric R. Ritchey, OD, PhD, FAAO
Review of Optometric Business, December 2018
Traditionally, optometry has managed myopia from a palliative approach, treating symptoms with spectacles and contact lenses while offering little in the way of a true treatment. The advent of refractive surgery offered patients an alternative to spectacles and contact lenses; however, this option did nothing to prevent the development of ocular disease associated with increased ocular growth. While myopia prevalence has been steadily increasing for over 40 years, our understanding of refractive error development and myopia progression have also increased.1-3 Today’s optometrist can finally offer our young myopes an alternative to traditional refractive error correction that can improve their quality of life and reduce their potential for future ocular disease. Today’s practitioners also have diagnostic tools at their disposal to effectively track the progression of myopia and determine if their treatment method is effective. In this article, we will discuss some of the technologies available to eyecare practitioners for the modern management of myopia.
- Flitcroft, D. I. (2012). The complex interactions of retinal, optical and environmental factors in myopia aetiology. Progress in retinal and eye research, 31(6), 622-660.
- Vongphanit, J., Mitchell, P., & Wang, J. J. (2002). Prevalence and progression of myopic retinopathy in an older population. Ophthalmology, 109(4), 704-711.
- Ogawa, A., & Tanaka, M. (1988). The relationship between refractive errors and retinal detachment–analysis of 1,166 retinal detachment cases. Japanese Journal of Ophthalmology, 32(3), 310-315.
- Lim, R., Mitchell, P., & Cumming, R. G. (1999). Refractive associations with cataract: the Blue mountains Eye Study. Investigative Ophthalmology & Visual Science, 40(12), 3021-3026.
TO TREAT OR NOT TO TREAT?
First, we need to address the question of why we should attempt to slow myopia progression. Often the parents of potential patients do not feel that being nearsighted is a significant health concern. While most patients consider myopia to be a nuisance or a relatively benign condition, myopia has become a worldwide epidemic. Epidemiologic studies have shown that the prevalence of myopia has been steadily increasing globally, with some countries in Southeast Asia reporting myopia prevalence of 90 percent or greater in young adults by the time they enter their twenties.4-6 The United States and Europe, while not seeing increases as large as those seen in Asia, have also shown a steady increase in myopia development.1, 7, 8 Along with the increase in myopia prevalence, the age of myopia onset is decreasing, meaning that the myopes we see in the future will most likely be more myopic than our current patients. The consequence of these changes is the development of future disease and quality of life for our patients. Myopia has been associated with a number of conditions, including increased odds for developing cataracts, open angle glaucoma and retinal detachment. High myopia, defined as worse than -5.00 or -6.00 diopters of myopia in most scientific publications, is associated with a number of conditions including posterior staphyloma, chorioretinal and RPE atrophy, and lacquer cracks. Most significant may be the development of myopic maculopathy, which includes macular hemorrhages, foveoschisis, macular holes and choroidal neovascularization (CNV). These conditions may lead to significant vision loss or blindness.9-16 With an increasing number of myopic patients and more myopia-related ocular disease, myopia will become an increasingly significant financial burden on public health infrastructure, not only from the cost of spectacles and contact lenses, but, also from the increased medical and surgical expenses associated with treating high myopia.17-20
Given these risks, the case for attempting to slow myopia progression is compelling. However, it is important to remember that currently there is no FDA-approved pharmacological or medical device treatment for the prevention of myopia development or for the slowing on myopia progression. All of the technologies we will discuss are used on an “off-label” basis. Off-label usage of medical devices and pharmaceuticals is a common and accepted practice in health care.
Per the FDA: “Good medical practice and the best interests of the patient require that physicians use legally available drugs, biologics and devices according to their best knowledge and judgement. If physicians use a product for an indication not in the approved labeling, they have the responsibility to be well informed about the product, to base its use on firm scientific rationale and on sound medical evidence, and to maintain records of the product’s use and effects.”
Given this, patients who wish to pursue myopia control treatment should be educated that use of any of these technologies is off-label, the risk and benefit from use of such treatment and this education should be recorded in the patient record.
It is well established that the eye has the ability to adapt its rate of growth to the visual environment. The work of Nobel Prize winners Hubel and Weisel led to early observations that animals become myopic when deprived of clear vision (i.e., form deprivation). This observation in animals was consistent with case reports of nearsightedness in children where the eye was partially or completely occluded due to eyelid hemangiomas, neonatal lid closure, ptosis or cataract.21-25 Beyond form deprivation, animal models have also shown that blur induced with lenses can alter ocular growth. Animals treated with plus-power lenses, generating myopic defocus, display slower rates of eye growth compared to eyes without treatment. The retina has the ability to detect the sign of optical defocus, thus when the eye detects myopic defocus, the rate of ocular growth decreased.26 Furthermore, this defocus does not need to be present at the fovea. Animals treated with lenses that have no power in the lens center but plus power in the lens periphery also demonstrate a reduction in ocular growth.27 This finding suggests that optical defocus in the retinal periphery is a significant factor in regulating optical growth. This observation from animals is also consistent with case reports on refractive error from humans where the retinal periphery undergoes significant damage as children. For example, children with Retinopathy of Prematurity (ROP) that undergo cryotherapy in the retinal periphery often become highly myopic. Another study found that children treated with avastin instead of laser therapy for ROP had significantly reduced amounts of high myopia, suggesting that an intact peripheral retina is required for emmetropization in humans.28
Based on the findings from basic science experiments, contact lenses have been used on an off-label basis for the control of myopia progression. The key to these treatments is the location of light relative to the retina. With traditional spectacle correction in myopia, light is focused on the macula, allowing for best visual acuity; however, in the retinal periphery, light falls behind the retina. The result is a peripheral image shell formed that falls behind the retina. This is referred to as relative peripheral hyperopia, and is considered a potential stimulus for ocular growth. Optics that reduce or eliminate relative peripheral hyperopia, which pulls the image shell closer to the retina or in front of the retina, would likely reduce myopia progression. Optical designs that incorporate additional plus power while maintaining good central acuity have the potential to shift the image shell. Contact lens technology available today, in the form of center-distance soft bifocal contact lenses and reverse-geometry orthokeratology lenses, can provide patients optical profiles to reduce relative peripheral hyperopia and slow myopia progression.
SOFT MULTIFOCAL CONTACT LENSES
Soft multifocal contact lenses with center-distance optics commonly used to correct presbyopia through a simultaneous vision effect have been examined for potential myopia control effects. A review of the published literature by Walline reported that the average myopia control effect with soft multifocal contact lenses was 46 percent.29 Center-distance multifocal contact lenses increase plus power in the lens periphery by using aspheric optics or concentric rings of additional plus. In presbyopes, this design provides correction for near work; however in children, this increase in plus power reduces relative hyperopic defocus, particularly with aspheric multifocal designs. Center-distance designs are used to allow children to have acceptable distance vision, where center-near designs would induce too much distance vision blur to be effective for daily wear. In the United States, commercially produced center-distance multifocal designs that have been utilized in myopia control included the Proclear and Biofinity Multifocal “D” lens (CooperVision), the NaturalVue Multifocal (Visioneering Technologies, Inc.) and custom soft contact lens manufacturers (e.g., SpecialEyes). Additionally, a multifocal contact lens designed for myopia control, the MiSight (CooperVision) contact lens, is available in Canada, Europe and other countries; however, the lens does not have FDA approval in the United States and is not available for purchase.
The Proclear and Biofinity soft multifocal contact lenses (CooperVision) utilize Balanced Progressive® Technology, a modified monovision system featuring two different aspheric lenses: a center-distance “D” lens and a center-near “N” lens, both with add powers ranging from +1.00 to 2.50 diopters in 0.50D steps. When using these lenses for myopia control, the center-distance “D” lens is used in each eye, with a recommendation to use the +2.50D add in each eye and the sphere power fit with a maximum plus power to maximum visual acuity approach. Using this approach, a small amount of negative power in the contact lens over-refraction is anticipated for maximum distance visual acuity; however, even with this addition minus sphere power, the lens is able to produce the desired optical effect in the retinal periphery.30 If acceptable distance vision cannot be obtained with over-refraction, the bifocal add power may be reduced. This approach allows children with up to 1.00 diopters astigmatism to be fit successfully with these lenses. If the child has -1.00D or more refractive astigmatism, the Proclear Toric Multifocal and the Proclear Toric Multifocal XR lens may be used to fit children with astigmatism up to -5.75D.
The NaturalVue Multifocal 1 Day contact lens (Visioneering Technologies, Inc.) is a center-distance aspheric multifocal design that utilizes an extended depth of focus principal. This design provides a multifocal effect for add power requirements up to +3.00D, and there is no add power selection. Initial lens power may be selected using the spherical equivalent refractive error of the subject, or by using the NaturalVue QuickStart Calculator (Apple App Store or Google Play). The clinician should then over-refract using a maximum plus to best visual acuity approach. Children with up to -1.00D of refractive astigmatism may be fit with the lens, and a toric multifocal option is currently not available. While the lens does not have an indication for myopia control from the USFDA, the lens does have a myopia control indication approval in Australia.
An alternative to mass produced commercially available lenses are custom manufactured soft multifocal contact lens options. SpecialEyes (https://specialeyesqc.com) produces two multifocal soft contact lens options: the 54 Multifocal Aspheric design and the 54 Bifocal 2-Zone Annular design made in hioxifilcon D 54 percent material. Both the 54 Multifocal and the 54 Bifocal lenses can be made in a center-distance design and offer clinicians the ability to customize the size of the center distance zone. Each design can be made in sphere and toric designs with an add power of up to +4.00D. Because of the custom nature of the product, the lenses are replaced on a quarterly basis.
The MiSight soft multifocal contact lens is a dual-focus, center-distance concentric ring multifocal with an indication for myopia control in Canada, Europe, Australia and select additional countries. The lens is available from -0.25D to -6.00D spherical power and is fit in children with -0.75D refractive astigmatism using the spherical equivalent refractive error. Three-year data from a multicenter clinical trial found a 59 percent reduction in mean cycloplegic spherical equivalent refractive error and 52 percent reduction in axial elongation with the MiSight Lens compared to children wearing a spherical contact lens.31 Recently released data from CooperVision at the BCLA Asia meeting discussed data from Year Four of the study, where the control subjects were refit from the single vision contact lens to the MiSight contact lens. Control subjects switched to the MiSight lens had a significant reduction in myopia progression, and the rate of axial elongation and spherical equivalent refractive error change was not significantly different between the two groups.32 Although the MiSight contact lens currently does not have FDA approval, the lens’ availability in Canada means that practitioners may field questions from their patients regarding the product.
Recommendation: Currently available soft multifocal contact lenses on the market may be used on an off-label basis to provide myopia control to pediatric patients. Lenses should be fit with a maximum plus to maximal visual acuity philosophy to avoid over-minusing patients and potentially reducing the myopia control effect. Patients requiring astigmatic correction have limited options, including the Proclear Toric Multifocal or a custom manufactured contact lens. Practitioners looking for a daily disposable option for off-label myopia control may consider the NaturalVue Multifocal contact lens.
RGP CONTACT LENSES AND MYOPIA MANAGEMENT
Spherical Rigid Gas Permeable (RGP) lenses had been recommended as potential myopia-control treatment options in the past; however, spherical RGP lenses are no longer considered an effective treatment option. While early studies suggested that these lenses may reduce progression, these studies often had significant limitations, including not measuring the axial growth of the eye. Research studies from Katz (2003) and Walline (2004) examining the ability of spherical RGP lenses to slow ocular growth with a-scan ultrasonography showed that spherical RGP lenses do not slow axial length growth.29 While the Walline study showed a significant refractive error effect, with RGP wearers showing less progression in spherical-equivalent refractive error for RGP wearers compared to soft contact lens wearers, the RGP wearers had significantly flatter corneal curvature, suggesting that the anecdotally-observed myopia control effects of these lenses in clinical practice was simply the outcome of corneal molding with flat fitting lenses.
While RGP sphere lenses do not slow axial length growth, orthokeratology contact lenses with reverse curve geometry do give us an opportunity to slow myopia progression. Reverse geometry orthokeratology lenses redistribute the corneal epithelium laterally from the central treatment zone, creating an annulus of plus power in the mid-peripheral cornea. The resultant annulus of positive power in the corneal mid-periphery reduces relative peripheral hyperopia for our patients.
Clinical research has shown that corneal reshaping with orthokeratology lenses does lead to a reduction in axial length growth. A review of the published literature by Walline reported that the average myopia control effect with orthokeratology contact lenses was 43 percent; however, most studies examining the effectiveness of orthokeratology for myopia control have limitations, such as lack of true randomization or being retrospective in design.29 A randomized clinical trial in Hong Kong, the ROMIO study, found a significant reduction in myopia progression with orthokeratogy lenses compared to subjects who wore single vision spectacles over a two-year period.33 An additional study by Charm and Cho found a myopia control effect is observed in highly myopic children (myopia of -5.00D or worse) even if overnight orthokeratology only partially corrects the child’s refractive error, and she needs to wear single vision spectacles to maximize distance vision.34 Although there are no published randomized clinical trials comparing the effectiveness of different orthokeratology designs, Kang and Swarbrick examined the relative refractive profiles generated by three different orthokeratology lenses (BE, Contex OK, Paragon CRT) in a sample of young adult myopes with mild to moderate myopia (-1.00 and -4.00 D myopia with ≤ 1.50D of with-the-rule corneal astigmatism) over a two-week wear period. Kang and Swarbrick found no differences in the peripheral refractive profile between the three lenses, suggesting that there would be no significant difference in treatment efficacy between the lenses if used for myopia control.35
Additional work gives additional insight into the ability of orthokeratology to control myopia progression. Recent work examining orthokeratology ability to slow myopia progression in children with fast progression (>1.00D), medium progression (0.50D to <1.00D) and slow progression (<0.50D) over the preceding seven months with spectacle wear found that orthokeratology was effective for slowing myopia progression regardless if the child was a fast, medium or slow progressor. Although orthokeratology was effective for all groups, children 6-9 years old displayed the greatest myopia control effect, and these children made up the majority of the fast progressors in the trial. These findings suggest that young myopic children are likely to be fast progressors and a myopia control options should be discussed accordingly.
Recommendation: Spherical RGPs do not provide a myopia control effect and should not be utilized. Overall evidence suggests that orthokeratology with reverse-geometry technology reduces myopia progression in children; however, there are relatively few randomized controlled clinical trials examining the effect. At this time, no evidence exists that suggests that one reverse-geometry orthokeratology lens is superior to another in controlling myopia progression. Younger children may benefit more from early intervention compared to older children.
SPECTACLE LENSES AND MYOPIA MANAGEMENT
Spectacles utilizing multifocal optics, (i.e., bifocal additions or progressive addition lenses or PALs), have been studied as potential myopia control devices due to theories of accommodative lag and/or near work being a stimulus for myopia progression. The results of these investigations have been underwhelming. Traditional bifocal spectacles have shown little or no clinical effect for controlling myopia progression. The most successful report comes from Cheng, et al., who examined the use of +1.50D Executive-style bifocal lenses and found a 39-percent reduction in myopia progression over a three-year period (2.06D progression single vision lens; 1.25D progression executive bifocal). Cheng also examined a +1.50D Executive-style bifocal that incorporated 3 prism-diopters of Base In Prism in each lens. These lenses also displayed a myopia control effect; however, this effect was not significantly different than the effect shown by the bifocal lenses without prism. While the study displayed a treatment effect, the study population was limited to Chinese-Canadian children with a history of at least a 0.50D progression the year prior to the beginning of the study, limiting the generalizability of the findings.36
Progressive addition lenses (PALs) have also been examined for myopia control in a number of studies. As with bifocal spectacle lenses, research on PALs indicate that these lenses are ineffective as myopia control devices. The Correction of Myopia Evaluation Trial (COMET) study followed 462 children over a three-year period assigned to wear either a PAL with a +2.00D add or a single vision lens. While the difference in refractive error was statistically different after three years of treatment, the dioptric difference was only 0.20D.37 Berntsen, et al. examined the use of PALs in children between the age of 6 and 11 years old with myopia between -0.75D and -4.50D and high lag of accommodation. Berntsen found a statistically significant treatment effect after 1 for the PAL group; however, the treatment effect of 0.18D was considered clinically insignificant. Berntsen also noted that accommodative lag was not associated with myopia progression.38
Novel spectacle lens designs have also been considered for myopia control. Sankaridurg, et al., investigated three novel spectacle lens designs in Chinese children between the ages of 6 and 16 years old that had between +1.00 to +2.00D in the lens periphery. After 12 months, no treatment effect was observed for any of the three lens types. A post-hoc analysis suggested that the one of the lens designs may provide some benefit for children between 6 and 12 years old with myopic parents.39 This lens is marketed in Canada by Zeiss as the MyoVision spectacle lens (https://www.zeiss.ca/vision-care/en_ca/products/eyeglass-lenses/single-vision-lenses/single-vision-myovision.html). Other novel spectacle lens designs are currently being evaluated as myopia control devices. In 2018, Hong Kong Polytechnic University released a press statement stating that they had created a spectacle lens in collaboration with HOYA Vision that has “micro-lens segments” in the mid-periphery of the lens. The “micro-lens segments” create myopic defocus and slowed myopia progression in a double-masked clinical trial.
Recommendation: Bifocal and Progressive Addition Spectacle lenses are not considered first line treatments for myopia control. Studies of these devices have shown statistically significant treatment effects, but often the observed effect is considered clinically insignificant. Novel spectacle lens designs are marketed outside the United States and are currently being developed; however, the potential efficacy of such devices in children in the United States is unknown.
ATROPINE AND MYOPIA MANAGEMENT
Numerous studies have shown that atropine is effective in slowing myopia progression; however, the side effects of mydriasis, cycloplegia, blurred vision and light sensitivity have limited the drug’s usefulness as a myopia control treatment. A dose-response effect is seen with atropine drops, with 1 percent atropine being the most effective dosage for slowing myopia progression; however, this is offset by the most severe side effects. Decreasing atropine concentration reduces side effects, but leads to reduced effectiveness. The side effect profile of atropine has led scientists to examine lower doses of atropine (e.g., 0.5 percent, 0.1 percent, 0.01 percent) in search of a dosage that provides a treatment effect with minimal side effects. The Atropine for the Treatment of Myopia research studies (ATOM and ATOM2) are perhaps the most influential clinical trials on the topic. The ATOM trial examined eyes of 6-12-year-old children treated with 1 percent atropine compared to eyes treated with vehicle (i.e., placebo) control. ATOM revealed a significant treatment effect for refractive error and axial elongation with 1 percent atropine over a two-year treatment period. Following the successful outcome from the ATOM study, the ATOM2 study examined the ability of 0.5 percent, 0.1 percent and 0.01 percent atropine drops to provide myopia control over a two-year period; however, there was no vehicle-only control group. The ATOM2 study reported a significant effect on myopia progression; however, with decreasing atropine concentration, a reduction in refractive error treatment effect was observed. ATOM2 also reported a reduction in axial elongation with atropine use, but this effect was greater with the 0.5 percent and 0.1 percent drops than with the 0.01 percent drops, suggesting that the 0.01 percent concentration drops may have a minimal impact on controlling axial elongation. This is supported when comparing data between the ATOM and ATOM2 studies; where the axial elongation observed in the ATOM study eyes treated with vehicle-only was not different than the axial elongation observed in eyes treated with 0.01 percent atropine in ATOM2. Both ATOM and ATOM2 completed a 12-month wash-out period where the subjects on atropine treatment were discontinued. A significant rebound effect in ocular growth was observed with 1 percent, 0.5 percent and 0.1 percent atropine, while a minimal rebound effect was observed with 0.01 percent atropine. This lack of rebound effect with 0.01 percent compared to higher percentage atropine drops further suggests that low-dose atropine has a minimal effect on modulating axial elongation.40, 41
Atropine has been examined as a combined therapy with orthokeratology lenses. Wan, et al., reported on the outcome from a retrospective study of subjects using 0.125 percent or 0.025 percent atropine drops with Euclid Emerald four-zone reverse-geometry orthokeratology lenses. The subjects in the study were assigned to a high myopia or low myopia group for analysis. The authors reported a synergistic effect between orthokeratology and atropine, with slower axial elongation with the combination treatment compared to orthokeratology alone.42
Recommendation: Myopia control with atropine occurs in a dose-dependent manner, with higher doses of atropine providing a greater treatment effect. Discontinuation of atropine leads to a rebound growth effect which limits the usefulness of the treatment. The effectiveness of low-dose atropine is controversial, with some reports promoting its use; however, low-dose atropine does not appear to effectively slow axial growth. Current research examining potential synergistic effects between atropine and contact lenses is promising; however, there is not enough information available to make a recommendation on combination treatments.
Myopia progression can be controlled using technology currently available to eyecare practitioners in the United States. Center-distance bifocal contact lenses and orthokeratology provide similar myopia control effects and may make recommendation for either modality based upon individual patient and parental needs. Atropine, while effective, can lead to significant rebound when discontinued, and low-dose atropine may not be effective at slowing ocular growth.
Eric R. Ritchey, OD, PhD, FAAO is an Assistant Professor at the University of Houston College of Optometry. He is an OD and PhD graduate of The Ohio State University College of Optometry. His clinical interests are in specialty contact lens fitting, anterior segment disease and ocular prosthetics. His research activities focus on myopia development and contact lenses.
- Vitale S, Sperduto RD, Ferris FL, 3rd. Increased Prevalence of Myopia in the United States between 1971-1972 and 1999-2004. Arch Ophthalmol 2009;127:1632-9.
- Sun J, Zhou J, Zhao P, et al. High Prevalence of Myopia and High Myopia in 5060 Chinese University Students in Shanghai. Invest Ophthalmol Vis Sci 2012;53:7504-9.
- Lam CS, Lam CH, Cheng SC, Chan LY. Prevalence of Myopia among Hong Kong Chinese Schoolchildren: Changes over Two Decades. Ophthalmic Physiol Opt 2012;32:17-24.
- Yoon KC, Mun GH, Kim SD, et al. Prevalence of Eye Diseases in South Korea: Data from the Korea National Health and Nutrition Examination Survey 2008-2009. Korean J Ophthalmol 2011;25:421-33.
- Edwards MH, Lam CS. The Epidemiology of Myopia in Hong Kong. Ann Acad Med Singapore 2004;33:34-8.
- Lin LL, Shih YF, Hsiao CK, Chen CJ. Prevalence of Myopia in Taiwanese Schoolchildren: 1983 to 2000. Ann Acad Med Singapore 2004;33:27-33.
- Jobke S, Kasten E, Vorwerk C. The Prevalence Rates of Refractive Errors among Children, Adolescents, and Adults in Germany. Clin Ophthalmol 2008;2:601-7.
- Rahi JS, Cumberland PM, Peckham CS. Myopia over the Lifecourse: Prevalence and Early Life Influences in the 1958 British Birth Cohort. Ophthalmology 2011;118:797-804.
- Iwase A, Araie M, Tomidokoro A, et al. Prevalence and Causes of Low Vision and Blindness in a Japanese Adult Population: The Tajimi Study. Ophthalmology 2006;113:1354-62.
- Kocur I, Resnikoff S. Visual Impairment and Blindness in Europe and Their Prevention. Br J Ophthalmol 2002;86:716-22.
- Mitchell P, Hourihan F, Sandbach J, Wang JJ. The Relationship between Glaucoma and Myopia: The Blue Mountains Eye Study. Ophthalmology 1999;106:2010-5.
- Saw SM, Gazzard G, Shih-Yen EC, Chua WH. Myopia and Associated Pathological Complications. Ophthalmic Physiol Opt 2005;25:381-91.
- Soubrane G. Choroidal Neovascularization in Pathologic Myopia: Recent Developments in Diagnosis and Treatment. Surv Ophthalmol 2008;53:121-38.
- Xu L, Wang Y, Li Y, et al. Causes of Blindness and Visual Impairment in Urban and Rural Areas in Beijing: The Beijing Eye Study. Ophthalmology 2006;113:1134 e1-11.
- Xu L, Wang Y, Wang S, Jonas JB. High Myopia and Glaucoma Susceptibility the Beijing Eye Study. Ophthalmology 2007;114:216-20.
- Yoshida T, Ohno-Matsui K, Yasuzumi K, et al. Myopic Choroidal Neovascularization: A 10-Year Follow-Up. Ophthalmology 2003;110:1297-305.
- Rein DB, Zhang P, Wirth KE, et al. The Economic Burden of Major Adult Visual Disorders in the United States. Arch Ophthalmol 2006;124:1754-60.
- Vitale S, Cotch MF, Sperduto R, Ellwein L. Costs of Refractive Correction of Distance Vision Impairment in the United States, 1999-2002. Ophthalmology 2006;113:2163-70.
- Lafuma A, Brezin A, Lopatriello S, et al. Evaluation of Non-Medical Costs Associated with Visual Impairment in Four European Countries: France, Italy, Germany and the Uk. Pharmacoeconomics 2006;24:193-205.
- Lim MC, Gazzard G, Sim EL, et al. Direct Costs of Myopia in Singapore. Eye (Lond) 2009;23:1086-9.
- Robb RM. Refractive Errors Associated with Hemangiomas of the Eyelids and Orbit in Infancy. Am J Ophthalmol 1977;83:52-8.
- O’Leary DJ, Millodot M. Eyelid Closure Causes Myopia in Humans. Experientia 1979;35:1478-9.
- Hoyt CS, Stone RD, Fromer C, Billson FA. Monocular Axial Myopia Associated with Neonatal Eyelid Closure in Human Infants. Am J Ophthalmol 1981;91:197-200.
- Rabin J, Van Sluyters RC, Malach R. Emmetropization: A Vision-Dependent Phenomenon. Invest Ophthalmol Vis Sci 1981;20:561-4.
- Nathan J, Kiely PM, Crewther SG, Crewther DP. Disease-Associated Visual Image Degradation and Spherical Refractive Errors in Children. Am J Optom Physiol Opt 1985;62:680-8.
- Wallman J, Winawer J. Homeostasis of Eye Growth and the Question of Myopia. Neuron 2004;43:447-68.
- Smith EL, 3rd. Prentice Award Lecture 2010: A Case for Peripheral Optical Treatment Strategies for Myopia. Optom Vis Sci 2010;88:1029-44.
- Geloneck MM, Chuang AZ, Clark WL, et al. Refractive Outcomes Following Bevacizumab Monotherapy Compared with Conventional Laser Treatment: A Randomized Clinical Trial. JAMA Ophthalmol 2014;132:1327-33.
- Walline JJ. Myopia Control: A Review. Eye Contact Lens 2016;42:3-8.
- Schulle KL, Berntsen DA, Sinnott LT, et al. Visual Acuity and over-Refraction in Myopic Children Fitted with Soft Multifocal Contact Lenses. Optom Vis Sci 2018;95:292-8.
- Three-Year Study Indicates Pioneering Contact Lens Therapy Effective in Slowing Myopia Progression in Children by 59%. https://coopervision.com/our-company/news-center/press-release/three-year-study-indicates-pioneering-contact-lens-therapy.
- Coopervision Releases Four-Year Data on Landmark Misight® 1 Day Contact Lens Study; Pioneering Approach Slows Myopia Progression in Children. https://coopervision.com/our-company/news-center/press-release/coopervision-releases-four-year-data-landmark-misight-1-day.
- Cho P, Cheung SW. Retardation of Myopia in Orthokeratology (Romio) Study: A 2-Year Randomized Clinical Trial. Invest Ophthalmol Vis Sci 2012;53:7077-85.
- Charm J, Cho P. High Myopia-Partial Reduction Ortho-K: A 2-Year Randomized Study. Optom Vis Sci 2013;90:530-9.
- Kang P, Swarbrick H. The Influence of Different Ok Lens Designs on Peripheral Refraction. Optom Vis Sci 2016;93:1112-9.
- Cheng D, Woo GC, Drobe B, Schmid KL. Effect of Bifocal and Prismatic Bifocal Spectacles on Myopia Progression in Children: Three-Year Results of a Randomized Clinical Trial. JAMA Ophthalmol 2014;132:258-64.
- Gwiazda J, Hyman L, Hussein M, et al. A Randomized Clinical Trial of Progressive Addition Lenses Versus Single Vision Lenses on the Progression of Myopia in Children. Invest Ophthalmol Vis Sci 2003;44:1492-500.
- Berntsen DA, Sinnott LT, Mutti DO, Zadnik K. A Randomized Trial Using Progressive Addition Lenses to Evaluate Theories of Myopia Progression in Children with a High Lag of Accommodation. Invest Ophthalmol Vis Sci 2012;53:640-9.
- Sankaridurg P, Donovan L, Varnas S, et al. Spectacle Lenses Designed to Reduce Progression of Myopia: 12-Month Results. Optom Vis Sci 2010;87:631-41.
- Chua WH, Balakrishnan V, Chan YH, et al. Atropine for the Treatment of Childhood Myopia. Ophthalmology 2006;113:2285-91.
- Chia A, Chua WH, Cheung YB, et al. Atropine for the Treatment of Childhood Myopia: Safety and Efficacy of 0.5%, 0.1%, and 0.01% Doses (Atropine for the Treatment of Myopia 2). Ophthalmology 2011;119:347-54.
- Wan L, Wei CC, Chen CS, et al. The Synergistic Effects of Orthokeratology and Atropine in Slowing the Progression of Myopia. J Clin Med 2018;7.