During the total 12-month study period, changes in refractive error were well predicted by changes in axial length (R2 = 0.64, p < 0.001) but not by changes in anterior chamber depth (R2 = −0.012; p = 0.79). Indeed, both the BFSCL and SVSCL groups recorded significant reductions rather than increases in anterior chamber depth (p < 0.01), presumably reflecting the growth of the crystalline lens in these young eyes, as the magnitude of the change was not significantly different between the groups (p = 0.94). There was no significant change of corneal curvature for either group during the 12-month treatment period (p = 0.40).
A series of multivariate analyses of variance were also conducted to identify potentially significant associations. Only the most efficient model, that is, with the least number of variables without affecting the goodness of fit of the model, is reported, with changes in axial length and in refractive error as dependent continuous variables and six independent variables, treatment, sex, age, baseline refractive error, baseline near associated phoria, and BFSCL add power. Of these six variables, only age, considered as a continuous variable, and contact lens treatment proved to be significantly associated with changes in refractive error and axial length (Wilks λ = 0.579, F2,74 = 26.86, p < 0.0001 for age; and Wilks λ = 0.533, F2,74 = 32.41, p < 0.0001 for contact lens treatment, respectively).
Our study specifically targeted subjects with near associated esophorias based on early reports linking near dissociated esophoria with better myopia control with multifocal spectacle lenses.31–33 As expected, the BFSCL group showed a significant reduction in residual associated esophorias (associated phoria measured with contact lenses in place) relative to that of the SVSCL group (−1.10 ± 0.52D vs. −0.16 ± 0.43D, p < 0.0001). Nonetheless, neither baseline associated phorias nor residual associated phorias were significantly associated with overall changes in refractive error (F1,73 = 0.17, p = 0.68; F1,73 = 1.13, p = 0.29 for baseline near associated phoria and change in near associated phoria across 12 months, respectively).
The CONTROL study described here provides compelling evidence for the efficacy of bifocal contact lenses as a myopia control treatment. The strong myopia control effect found in this study, that is, an overall 72% reduction in progression, based on cycloplegic autorefraction, and 80% reduction in the rate of axial elongation, far exceeds the size of treatment effects reported in previous myopia control studies involving optical devices in humans,29–31,39,39–41 and only daily 1.0% topical atropine has comparable results of the pharmacological treatments studied.40 Nonetheless, the results are consistent with an already published identical twin case study by the authors.41 However, the CONTROL study provides more convincing evidence that myopia progression can be effectively controlled through optical intervention, being a well-controlled, albeit small-scale, double-masked clinical trial with treatments randomly assigned and groups well matched with regard to sex, ethnicity, refractive error, and degree of near associated phoria. As a 12-month study, it is not possible to comment on the enduring nature of this treatment effect, although related more recent contact lens studies have reported significant treatment effects beyond the first year.42,43 Given that many of the sight-threatening ocular complications of myopia are linked to excessive ocular elongation,5,44 it is also important to note that the BFSCL control effect reported here was achieved through reduced ocular elongation.
The large control effects reported here contrast with the somewhat small effects reported in two COMET studies,45,46 which represent the largest and best-controlled of clinical trials involving multifocal spectacle lenses for myopia in children to date. Both COMET studies used progressive addition lenses (PALs). In the first study, subgroup analyses revealed that subjects with either low baseline levels of myopia and reduced accommodative responses or near esophoria and larger than normal lags of accommodation all benefited significantly from PALs, recording treatment effects of 0.55 and 0.64D less myopia progression, respectively, across 3 years compared with that of single-vision spectacle wearers. The reduction in progression rates with PALs was 0.20D overall, and for near exophores, 0.05D. Curiously, in a 3-year follow-up study (COMET II), which was limited to children with high accommodative lags and near esophoria,46 the treatment effect was very small, averaging 0.28D, and another shorter study (STAMP),47 which was likewise limited to children with high accommodative lags, also reported only a small, 0.18D, treatment effect across 12 months. Additional selection criteria for the latter study included either myopia less than −2.25D or myopia higher than −2.25D combined with esophoria at near. Although all three studies were United States based, results from studies involving multifocal spectacles in East Asia have also not revealed consistent clinically significant myopia control benefits for those with near esophorias or high lags of accommodation.48,49
Since the completion of the study reported here, there have been a number of other myopia control–related bifocal contact lens studies, and as reported here, most have demonstrated better efficacy than related multifocal spectacle lens studies. Two such studies, the DISC study50 and the Dual Focus51 study, involved two different custom multifocal soft contact lens designs, which both had distance and near powers arranged in some form of multiple concentric rings, as with the lens design used in the current study. Both studies reported significant slowing of myopia progression in the wearers of their device relative to those receiving the single-vision control treatment, although less than in the current study, that is, 36% slower progression in both the DISC study overall and in the first 10 months of the crossover Dual Focus study. In the first year of yet another multiyear study comparing myopia progression with a soft contact lens design with peripheral plus power and single-vision soft contact lenses, an adjusted 34% relative reduction was reported.52 Finally, a 1-year study comparing myopia progression in wearers of a distance center multifocal soft lens with a +2.00D add with historical controls involving wearers of single-vision daily disposable soft contact lenses reported a 50% relative reduction in myopia progression and a 29% relative reduction in axial elongation.53
The arguments presented above rest on an assumption that accommodative lags stimulate eye elongation, that the adds in bifocal lenses and PALs served to correct them, and that the superiority of bifocal contact lenses reflects the near addition being available at all angles of gaze and near distances. A number of studies have attempted to directly measure the effects of bifocal soft contact lenses on accommodation, with significant differences in their outcomes. In one such study, myopes as well as emmetropes were reported to overaccommodate when wearing bifocal soft contact lenses, whereas only emmetropes showed this behavior for single-vision contact lenses incorporating the near addition power and only at some distances.56 However, two other studies have reported near normal accommodation in nonpresbyopic users of bifocal contact lenses,50,51 suggesting that they ignored the near zones of the lenses. Although different methodologies, including instrumentation, were used in these three studies, nonetheless, taken together, these results suggest that a simple analogy between bifocal spectacles and bifocal contact lenses is not appropriate here. Induced changes in net optical aberrations, including spherical aberration, are likely to also impact on accommodation, greater in the case of bifocal contact lenses than equivalent spectacle lenses, and these effects are also likely to be lens design dependent,57,58 a subject of an ongoing study. The possibility that such changes might contribute to the apparently greater efficacy of some bifocal contact lens designs cannot be ruled out.58
It is perhaps important to note that all CONTROL subjects exhibited near associated esophorias, with the bifocal adds being selected to maximally neutralize them and without which they could be expected to exhibit larger lags of accommodation as reduced accommodative effort is one way of reducing accommodative convergence by way of compensating for near esophorias. Based on animal model studies, the resulting retinal (hyperopic) defocus can be expected to contribute to myopic progression and bifocal adds to slow progression by attenuating such focusing errors. In this context, myopes exhibiting near eso-fixation disparities may represent a special subset likely to benefit significantly from near additions. Note also that most other multifocal lens studies have used standardized additions, with no selection criteria related to binocular vision status, perhaps contributing to the lower efficacies reported.
Other characteristics of bifocal soft contact lenses may also have contributed to their apparently greater effectiveness than spectacle lenses as myopia control treatments. Specifically, the improved efficacy of bifocal contact lenses over their spectacle lens equivalents may be related to differences in the defocus experience, including more sustained myopic defocus provided with the former. Animal studies have shown that the imposition of sustained myopic defocus over a sufficiently large area of retina (central or peripheral) strongly inhibits eye growth.21 The designers of the DISC study have argued that their contact lens imposes frequent near constant myopic defocus, distributed relatively evenly across the retina, thereby providing a robust stop signal to eye growth. The bifocal contact lens design used in the current study included alternating rings of distance and near powers. Interestingly, Fresnel spectacle lens designs incorporating rings of positive power have also been shown to have strong inhibitory effects on eye growth in both chick and guinea pig models.20,21,23The prolate eye shape commonly linked to human myopia may also be of relevance, as it is generally coupled to peripheral hyperopic defocus, which will be reduced, or even reversed in sign, at least during distance viewing, with bifocal contact lens designs incorporating peripheral adds, as used in the current study. The myopia control effect of such lenses would also be improved further if, during near viewing, nonpresbyopic wearers did not reduce their accommodation, as reported in two of the studies described above.37,38
No clinical trial is without its limitations. Limiting our subjects to those having eso fixation disparity at near prevents generalization of our conclusions about the treatment effects found with BFSCLs. The relatively short duration of our study is also a limitation. A follow-up longer-term study is needed to address the question of whether good control over myopia progression is maintained with BFSCLs beyond 12 months. Future studies should also aim for a more balanced representation by sex and include a wider range of ethnicities to cover the possibility of genetic differences in the evolution of myopia, as proposed by Yang et al.,49 among others. Finally, it will also be important to understand how early intervention influences the course of later progression on discontinuation of treatment.
Thomas A. Aller
Supported in part by a grant from Vistakon, a Division of Johnson and Johnson. Solutions were provided by Alcon. The first author has less than 50 shares of stock in Johnson and Johnson, a manufacturer of some of the bifocal and standard lenses used in the study, purchased in 1983. The first author has received a patent on the use of bifocal contact lenses for myopia progression control (U.S. Patent No. 6,752,499 B2; issued June 22, 2004), and he is a coauthor of several other patents in the area of myopia control.
Results of the study have been previously reported in abstract form at the International Myopia Conference, Singapore, 2006, and at the American Academy of Optometry meeting in Denver, Colorado, November 12, 2014.
Received April 5, 2015; accepted November 3, 2015.
1. Lin LL, Shih YF, Lee YC, Hung PT, Hou PK. Changes in ocular refraction and its components among medical students—a 5-year longitudinal study. Optom Vis Sci 1996; 73: 495–8.
2. Sun J, Zhou J, Zhao P, Lian J, Zhu H, Zhou Y, Sun Y, Wang Y, Zhao L, Wei Y, Wang L, Cun B, et al. High prevalence of myopia
and high myopia
in 5060 Chinese university students in Shanghai. Invest Ophthalmol Vis Sci 2012; 53: 7504–9.
3. Jung SK, Lee JH, Kakizaki H, Jee D. Prevalence of myopia
and its association with body stature and educational level in 19-year-old male conscripts in Seoul, South Korea. Invest Ophthalmol Vis Sci 2012; 53: 5579–83.
4. Vitale S, Ellwein L, Cotch MF, Ferris FL 3rd, Sperduto R. Prevalence of refractive error in the United States, 1999–2004. Arch Ophthalmol 2008; 126: 1111–9.
5. Flitcroft DI. The complex interactions of retinal, optical and environmental factors in myopia
aetiology. Prog Retin Eye Res 2012; 31: 622–60.
6. Iwase A, Araie M, Tomidokoro A, Yamamoto T, Shimizu H, Kitazawa Y, Tajimi Study G. Prevalence and causes of low vision and blindness in a Japanese adult population: the Tajimi Study. Ophthalmology 2006; 113: 1354–62.
7. Wu L, Sun X, Zhou X, Weng C. Causes and 3-year-incidence of blindness in Jing-An District, Shanghai, China 2001–2009. BMC Ophthalmol 2011; 11: 10.
8. Saw SM, Wu HM, Seet B, Wong TY, Yap E, Chia KS, Stone RA, Lee L. Academic achievement, close up work parameters, and myopia
in Singapore military conscripts. Br J Ophthalmol 2001; 85: 855–60.
9. Mirshahi A, Ponto KA, Hoehn R, Zwiener I, Zeller T, Lackner K, Beutel ME, Pfeiffer N. Myopia
and level of education: results from the Gutenberg Health Study. Ophthalmology 2014; 121: 2047–52.
10. Rose KA, Morgan IG, Ip J, Kifley A, Huynh S, Smith W, Mitchell P. Outdoor activity reduces the prevalence of myopia
in children. Ophthalmology 2008; 115: 1279–85.
11. Wallman J, Winawer J. Homeostasis of eye growth and the question of myopia
. Neuron 2004; 43: 447–68.
12. Wildsoet CF. Active emmetropization—evidence for its existence and ramifications for clinical practice. Ophthalmic Physiol Opt 1997; 17: 279–90.
13. Wildsoet C, Wallman J. Choroidal and scleral mechanisms of compensation for spectacle lenses in chicks. Vision Res 1995; 35: 1175–94.
14. Hammond DS, Wallman J, Wildsoet CF. Dynamics of active emmetropisation in young chicks–influence of sign and magnitude of imposed defocus. Ophthalmic Physiol Opt 2013; 33: 215–26.
15. Wildsoet C. Neural pathways subserving negative lens-induced emmetropization in chicks—insights from selective lesions of the optic nerve and ciliary nerve. Curr Eye Res 2003; 27: 371–85.
16. Smith EL 3rd, Kee CS, Ramamirtham R, Qiao-Grider Y, Hung LF. Peripheral vision can influence eye growth and refractive development in infant monkeys. Invest Ophthalmol Vis Sci 2005; 46: 3965–72.
17. Smith EL 3rd, Hung LF, Huang J, Blasdel TL, Humbird TL, Bockhorst KH. Effects of optical defocus on refractive development in monkeys: evidence for local, regionally selective mechanisms. Invest Ophthalmol Vis Sci 2010; 51: 3864–73.
18. Wallman J, Gottlieb MD, Rajaram V, Fugate-Wentzek LA. Local retinal regions control local eye growth and myopia
. Science 1987; 237: 73–7.
19. Charman WN, Radhakrishnan H. Peripheral refraction and the development of refractive error: a review. Ophthalmic Physiol Opt 2010; 30: 321–38.
20. Liu Y, Wildsoet C. The effect of two-zone concentric bifocal spectacle lenses on refractive error development and eye growth in young chicks. Invest Ophthalmol Vis Sci 2011; 52: 1078–86.
21. Liu Y, Wildsoet C. The effective add inherent in 2-zone negative lenses inhibits eye growth in myopic young chicks. Invest Ophthalmol Vis Sci 2012; 53: 5085–93.
22. Benavente-Pérez A, Nour A, Troilo D. Axial eye growth and refractive error development can be modified by exposing the peripheral retina to relative myopic or hyperopic defocus. Invest Ophthalmol Vis Sci 2014; 55: 6765–73.
23. McFadden SA, Tse DY, Bowrey HE, Leotta AJ, Lam CS, Wildsoet CF, To CH. Integration of defocus by dual power Fresnel lenses inhibits myopia
in the mammalian eye. Invest Ophthalmol Vis Sci 2014; 55: 908–17.
24. Smith EL 3rd. Spectacle lenses and emmetropization: the role of optical defocus in regulating ocular development. Optom Vis Sci 1998; 75: 388–98.
25. Atchison DA, Jones CE, Schmid KL, Pritchard N, Pope JM, Strugnell WE, Riley RA. Eye shape in emmetropia and myopia
. Invest Ophthalmol Vis Sci 2004; 45: 3380–6.
26. Chen C, Cheung SW, Cho P. Myopia control
using toric orthokeratology (TO-SEE study). Invest Ophthalmol Vis Sci 2013; 54: 6510–7.
27. Cho P, Cheung SW, Edwards M. The longitudinal orthokeratology research in children (LORIC) in Hong Kong: a pilot study on refractive changes and myopic control. Curr Eye Res 2005; 30: 71–80.
28. Santodomingo-Rubido J, Villa-Collar C, Gilmartin B, Gutierrez-Ortega R. Myopia control
with orthokeratology contact lenses in Spain: refractive and biometric changes. Invest Ophthalmol Vis Sci 2012; 53: 5060–5.
29. Walline JJ, Jones LA, Sinnott LT. Corneal reshaping and myopia
progression. Br J Ophthalmol 2009; 93: 1181–5.
30. Kang P, Swarbrick H. Time course of the effects of orthokeratology on peripheral refraction and corneal topography. Ophthalmic Physiol Opt 2013; 33: 277–82.
31. Goss DA, Grosvenor T. Rates of childhood myopia
progression with bifocals as a function of nearpoint phoria: consistency of three studies. Optom Vis Sci 1990; 67: 637–40.
32. Fulk GW, Cyert LA, Parker DE. A randomized trial of the effect of single-vision vs. bifocal lenses on myopia
progression in children with esophoria
. Optom Vis Sci 2000; 77: 395–401.
33. Gwiazda JE, Hyman L, Norton TT, Hussein ME, Marsh-Tootle W, Manny R, Wang Y, Everett D. Accommodation and related risk factors associated with myopia
progression and their interaction with treatment in COMET children. Invest Ophthalmol Vis Sci 2004; 45: 2143–51.
34. Aller TA, Wildsoet C. Results of a one-year prospective clinical trial (CONTROL) of the use of bifocal soft contact lenses to control myopia
progression. Ophthal Physiol Opt 2006; 26(Suppl. 1): 6.
35. Aller T, Wildsoet C, Liu M. CONTROL: a 12 month, randomized bifocal soft contact lens trial targeting myopia
progression. Optom Vis Sci 2014; 91:E-abstract 140007.
36. Zelen M. Randomized consent designs for clinical trials: an update. Stat Med 1990; 9: 645–56.
37. Fleiss JL, Levin B, Paik MC. Statistical Methods for Rates and Proportions, 3rd ed. J. Wiley: Hoboken, NJ; 2003.
39. Hasebe S, Ohtsuki H, Nonaka T, Nakatsuka C, Miyata M, Hamasaki I, Kimura S. Effect of progressive addition lenses on myopia
progression in Japanese children: a prospective, randomized, double-masked, crossover trial. Invest Ophthalmol Vis Sci 2008; 49: 2781–9.
40. Chua WH, Balakrishnan V, Chan YH, Tong L, Ling Y, Quah BL, Tan D. Atropine for the treatment of childhood myopia
. Ophthalmology 2006; 113: 2285–91.
41. Aller TA, Wildsoet C. Bifocal soft contact lenses as a possible myopia control
treatment: a case report involving identical twins. Clin Exp Optom 2008; 91: 394–9.
42. 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.
43. Hiraoka T, Kakita T, Okamoto F, Takahashi H, Oshika T. Long-term effect of overnight orthokeratology on axial length elongation in childhood myopia
: a 5-year follow-up study. Invest Ophthalmol Vis Sci 2012; 53: 3913–9.
44. Saw SM, Gazzard G, Shih-Yen EC, Chua WH. Myopia
and associated pathological complications. Ophthalmic Physiol Opt 2005; 25: 381–91.
45. Gwiazda J, Hyman L, Hussein M, Everett D, Norton TT, Kurtz D, Leske MC, Manny R, Marsh-Tootle W, Scheiman M. 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.
46. Gwiazda J, Chandler DL, Cotter SA, Everett DF, Hyman L, Kaminski BM, Kulp MT, Lyon DW, Manny RE, Marsh-Tootle WL, Matta NS, Melia BM, et al. Progressive-addition lenses versus single-vision lenses for slowing progression of myopia
in children with high accommodative lag and near esophoria
. Correction of Myopia
Evaluation Trial (COMET) 2 Study Group for the Pediatric Eye Disease Investigator Group. Invest Ophthalmol Vis Sci 2011; 52: 2749–57.
47. 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.
48. Edwards MH, Li RW, Lam CS, Lew JK, Yu BS. The Hong Kong progressive lens myopia control
study: study design and main findings. Invest Ophthalmol Vis Sci 2002; 43: 2852–8.
49. Yang Z, Lan W, Ge J, Liu W, Chen X, Chen L, Yu M. The effectiveness of progressive addition lenses on the progression of myopia
in Chinese children. Ophthalmic Physiol Opt 2009; 29: 41–8.
50. Lam CS, Tang WC, Tse DY, Tang YY, To CH. Defocus Incorporated Soft Contact (DISC) lens slows myopia
progression in Hong Kong Chinese schoolchildren: a 2-year randomised clinical trial. Br J Ophthalmol 2014; 98: 40–5.
51. Anstice NS, Phillips JR. Effect of dual-focus soft contact lens wear on axial myopia
progression in children. Ophthalmology 2011; 118: 1152–61.
52. Sankaridurg P, Holden B, Smith E 3rd, Naduvilath T, Chen X, de la Jara PL, Martinez A, Kwan J, Ho A, Frick K, Ge J. Decrease in rate of myopia
progression with a contact lens designed to reduce relative peripheral hyperopia: one-year results. Invest Ophthalmol Vis Sci 2011; 52: 9362–7.
53. Walline JJ, Greiner KL, McVey ME, Jones-Jordan LA. Multifocal contact lens myopia control
. Optom Vis Sci 2013; 90: 1207–14.
54. Hasebe S, Nakatsuka C, Hamasaki I, Ohtsuki H. Downward deviation of progressive addition lenses in a myopia control
trial. Ophthalmic Physiol Opt 2005; 25: 310–4.
55. 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.
56. Tarrant J, Severson H, Wildsoet CF. Accommodation in emmetropic and myopic young adults wearing bifocal soft contact lenses. Ophthalmic Physiol Opt 2008; 28: 62–72.
57. Tarrant J, Roorda A, Wildsoet CF. Determining the accommodative response from wavefront aberrations. J Vis 2010; 10: 4.
59. Swarbrick HA, Alharbi A, Watt K, Lum E, Kang P. Myopia control
during orthokeratology lens wear in children using a novel study design. Ophthalmology 2015; 122: 620–30.
60. Tong L, Huang XL, Koh AL, Zhang X, Tan DT, Chua WH. Atropine for the treatment of childhood myopia
: effect on myopia
progression after cessation of atropine. Ophthalmology 2009; 116: 572–9.
61. Garner LF, Stewart AW, Owens H, Kinnear RF, Frith MJ. The Nepal Longitudinal Study: biometric characteristics of developing eyes. Optom Vis Sci 2006; 83: 274–80.
62. Troilo D, Nickla DL, Wildsoet CF. Choroidal thickness changes during altered eye growth and refractive state in a primate. Invest Ophthalmol Vis Sci 2000; 41: 1249–58.
63. Wallman J, Wildsoet C, Xu A, Gottlieb MD, Nickla DL, Marran L, Krebs W, Christensen AM. Moving the retina: choroidal modulation of refractive state. Vision Res 1995; 35: 37–50.
64. Chakraborty R, Read SA, Collins MJ. Hyperopic defocus and diurnal changes in human choroid and axial length. Optom Vis Sci 2013; 90: 1187–98.
65. Poukens V, Glasgow BJ, Demer JL. Nonvascular contractile cells in sclera and choroid of humans and monkeys. Invest Ophthalmol Vis Sci 1998; 39: 1765–74.