In the last of this series of articles on myopia, we will consider the two further mechanisms that have been proposed for myopia control. These are the:

i Novel spectacle options.

ii Pharmacological interventions.

Novel spectacle options

Existing design trials

In the first article of this series the role of accommodation and AC/A ratio in the development of myopia was indicated as a possible environmental risk.1-3 In response to this finding, a number of studies have looked at the provision of multifocal or bifocal spectacles in order to control the rate of progression of myopia. A case report in 1947 reported the possibility of myopia control using bifocal lenses.4

In 1986, Goss5 carried out a retrospective analysis of myopia progression in a group of children aged between six and 15 years of age. The children had worn either single vision or bifocal spectacles throughout the period of the study. The bifocals used had either a +0.75 or +1.00DS addition and were generally prescribed where children showed either a near esophoria or accommodative infacility. Goss concluded that, while those children fitted with bifocals showed a slower rate of myopia progression, this did not reach statistical significance. Further analysis of the group found that, when the children were divided on the grounds of their phorias, esophoric children treated with bifocals did show a statistically significant reduction in myopia progression. Fulk et al6 found similar results in their group of esophoric children followed for 30 months. In this case, bifocal wear was responsible for a 0.25DS reduction in myopia progression.

In 2014, Cheng et al7 published their findings from a three-year trial of children using bifocal or prismatic bifocals in order to control their myopia. Children in this study were of Chinese ethnicity but living in Ontario, Canada, and had shown myopia progression of at least 0.50DS in the previous year. They were randomly assigned to wear either:

  • A single vision lens.
  • An executive bifocal with a +1.50DS addition.
  • An executive bifocal with a +1.50DS addition and 3Δ base in each of the segments.

The addition power and use of prisms was based on an earlier study conducted by the group on accommodative lag and horizontal phorias in Chinese children.8 The +1.50DS addition reduced the accommodative lag but did not induce significant near exophoria. The addition of prisms in the final group reduced the near exophoria to virtually zero. At the three-year conclusion, the bifocal and prismatic bifocal lenses had produced a statistically significant reduction in myopia progression when compared with the single vision lens. The highest effect was seen in the first year of the study with decreasing efficacy in years two and three. There was no statistically significant difference between the two forms of bifocal. Cheng et al suggest that it is the spectacle-induced near phoria which is a factor in myopia progression and not the magnitude of the child’s initial phoria. Both bifocal lens designs used would eliminate the near induced phoria. One concern must be that an executive bifocal with 3Δ base in could not be considered to be a cosmetically acceptable lens. It would be useful to know therefore if they were more effective in any specific group of children. In this case, the group found that the prismatic bifocal did produce a significant reduction of progression when compared to the bifocal in children with a low lag of accommodation (<1.01DS).

The following studies evaluate the use of multifocal lenses, ie progressive addition lenses (PALs). In 1999 Leung and Brown9 followed a group of Chinese schoolchildren over a two year period. The children were aged between nine and 12 years old and were randomly assigned to either single vision or PAL spectacles. Two levels of reading addition (+1.50 or +2.00 DS) were provided because of limited availability of lenses with the lower addition at the time. Decisions on which children were fitted with the multifocal lenses were based purely on their clinic record number. The group concluded that the PALs were associated with a lower rate of myopia progression when compared with the single vision group, the higher addition lenses having a greater effect on the rate of progression. The lack of additional selection criteria in the provision of the multifocals means that the true efficacy of the myopia control is more difficult to evaluate. Edwards et al10 also assessed the use of PALs versus single vision lenses. Participants in this study were not selected on the basis of the children’s near phoria or accommodative lag. They found that there was no statistically or clinically significant reduction in myopia progression between the two groups.

The Correction of Myopia Evaluation Trial (COMET) group published their findings on the use of progressive lenses in children with high accommodative lag and near esophoria in 2011.11 Inclusion criteria required that the children involved had a near esophoria of ≥ 2.00Δ and an accommodative lag of 1.00D –that is, < 2.00D accommodative response for a 3.00D demand. All of the multifocal lenses had a +2.00 addition. Over the three years of the study, a reduction of -0.27DS in myopia progression was found.

In 2012 Berntsen et al12 conducted a two-year study in which children wore single vision lenses or PALs for one year and then both groups wore single vision lenses for the following year. As with the COMET study all of the PALs had a +2.00D addition. The selection criteria for these children were the same as those used in the COMET paper.11 At the end of the two years of the study, they found there was no significant difference in myopia progression between the two groups of children.

Compliance

One of the challenges with providing children and young people with bifocal or PAL lenses is that of compliance with their correct use. Despite their accommodative lag, children have sufficient accommodation available to read clearly through the distance portion of the lens. Inappropriate use of the spectacles would clearly negate the investigations being undertaken. Goss5 checked compliance with bifocal wear at each visit by watching the child read and checking the fit of the spectacles. Where children were non-compliant with their reading position, they were reinstructed in the use of the spectacles. Frame fittings were adjusted to ensure that the bifocal segment sat 1mm above the lower limbus.

Cheng et al7 offered no information regarding fitting parameters in their study, although they did suggest the executive bifocal design may act as a prompt to the child to encourage appropriate lens use. Leung et al9 and Edwards et al10 reported the fitting of their PALs as being 1mm above the pupil height. This decision was based on a study by Hasebe et al13 who looked at the downward deviation of the PALs over time in a myopia control study. In the case of a presbyopic adult they would have raised their chin or moved their eyes down to achieve maximum near clarity if the lenses slipped down. Hasebe et al found that on average the lenses slipped down by 3.7 +/-2mm between visits which reduced the efficacy of the near portion by between 30 and 63%. The group suggest that the variation in the effect of either bifocals or PALs on myopia progression may relate to a lack of appropriate fitting of the lenses during the duration of the study. In 2011 Cheng, Woo and Schmid14 produced a review of the use of bifocal lenses in myopia control. They conclude that these lenses have a place to play in the control of myopia but that new novel lens designs were required to allow further control.

Specialised design trials

In the second article in the series (Optician 03.12.16), the role of peripheral refraction in myopia progression was introduced. Orthokeratology, soft multifocal and custom designed contact lenses, exploit this phenomenon in their action in myopia control. Recent spectacle lenses have been designed to manipulate the peripheral refraction in a similar manner. These lenses are referred to as radial refractive gradient lenses (RRGs). These lenses show increasing positive power as you move from the optical centre to the periphery in all directions.

Tabernero et al15 reported on the peripheral refraction found when a group of adults were corrected using RRG lenses. They found that the lenses did induce a myopic periphery but that the effects varied dramatically dependent upon the relative position of the eye and the spectacle lens. This contrasts with the effect of orthokeratology lenses for example when the eye and lens relationship remain constant. A significant problem with these RRG lenses is the induced distortion which is similar to that found in conventional PAL designs. As we know, the minimisation of peripheral distortion has occupied PAL lens design manufacturers over many years.

Sankaridurg et al reported their findings on novel spectacle lens designs in 2010.16 The group recruited 210 Chinese children to the study which involved the use of three different novel lenses designed to reduce peripheral hyperopic defocus.

  • Lens 1 was a rotationally symmetrical lens designed to produce 1.00D of relative peripheral power.
  • Lens 2 was a similar design but produced 2.00D of relative peripheral hyperopic defocus.
  • Lens 3 was an asymmetric design which was designed to minimise horizontal astigmatism and produce a relative peripheral hyperopic defocus of 1.90D in the lower portion of the lens.

For control purposes, a standard single vision lens was also included. Lenses 1 and 2 were RRG lenses while Lens 3 was a novel design as indicated. All three lenses created a reduction in the progression of myopia when compared to the standard single vision lens. The third lens design had the greatest effect on the rate of myopia progression but none of the lenses produced an effect of statistical significance at the 12-month evaluation of the whole group. A subgroup of younger children in the study (six to 12 years age) who also demonstrated a history of parental myopia did show a statistically significant change in their myopia progression.  Sankadurig et al point out that further evaluation of the lens designs in younger children may allow them to play a part in the armoury of interventions for myopia control. The group also noted that, as with other PAL studies,9-12 children wearing these lenses did not adopt the optimum gaze point when reading. The children tended to lower their heads to read rather than lower their eyes as would be the expected case for progressive power lenses. This lack of optimum position could have limited the efficacy of the lenses.

In 2014 Hasebe et al17 reported their findings on the use of another novel PAL designed lens. These lenses are referred to as ‘positively aspherized’ progressive addition lenses (PA-PAL). In these lenses, the lower portion of the lens is designed to reduce lag of accommodation and the periphery to reduce hyperopic defocus. Children were recruited to the study and divided between two PA-PAL lens designs and a single vision control. The first lens induced a +1.00DS reading addition and periphery while the second induced a +1.50DS addition and periphery. Both lenses were designed with a short intermediate corridor to improve the likelihood that children would read through the reading zone. The overall effect of the +1.50DS induced lens after a two-year follow up was similar to that seen with conventional PALs (-0.27DS). The major retardation effects occurred in the first 12 months. The +1.00DS lens showed no statistically significant treatment effect over the two-year period. The additional complexity involved in producing these lenses is therefore unjustified in the control of myopia.

Clearly, PALs would provide a more cosmetically acceptable spectacle lens than an executive bifocal. As fewer and fewer bifocals are prescribed commercially, then the availability of the technology to produce these lenses will also disappear. For either bifocal or PALs caution must always be applied in assessing their effects since statistically significant changes may not constitute clinically significant ones. Most of the research groups reported in this article found a maximum effect in the first year with limited success thereafter. It may be that, with further research, PALs could prove to be a possible alternative for myopia control in children unable to tolerate contact lenses. Another mechanism for these children may be the use of pharmacological interventions.

Pharmacological interventions

The principle involved in pharmacological interventions is the binding of muscarinic receptors; in the case of atropine, the M3 receptors which are involved in accommodation and mydriasis and the M1 receptors which are involved in eye growth. Much of the initial work in pharmacological intervention is based on animal models of myopia and myopia control. This work is outside the scope of this article.

In 2006 Wei-Han et al18 reported on the use of atropine 1% in the control of myopia in children. The ATOM study used a double masked placebo controlled trial to look at the suitability of the use of atropine in children. Four hundred children aged between six and 12 years of age with myopia between -1.00 and -6.00DS were recruited. Participants were assigned to receive either 1% atropine drops or a placebo drop containing hydroxypropyl methyl cellulose in one eye. Myopia progression was evaluated over a two-year period. The eyes treated with atropine showed myopia progression of -0.28 +/- 0.92D while the placebo treated eyes showed an increase in myopia of -1.20 +/- 0.69D. Axial length measurements had increased in the placebo treated eyes by 0.38 +/- 0.38mm while the atropine treated eyes showed no significant increase in axial length. The untreated eye in each of the children had undergone myopia progression in line with that of the placebo treated eyes. The group acknowledged that the dilemma in this case was that, while treatment with atropine in one eye allows the children to maintain clear near vision in the untreated eye, this eye will continue to show myopic progression.

It is clearly unacceptable to render a child significantly anisometropic. If, however, both eyes are treated, then children will require some form of multifocal spectacle in order to achieve clear near vision. A similar study by Yi et al19 in children with low myopia (-0.50 – -2.00DS) gave similar results for both refractive error and axial length changes. In fact, for the atropine treated eyes, myopia had decreased by 0.32 +/- 0.22D at the end of the study. Many of the studies into the use of atropine have taken place in largely Asian populations. Li et al20 found in their meta-analysis that atropine was more effective in Asian rather than Caucasian children. In a recently published study in Rotterdam,21 the use of 0.5% atropine eye drops was found to be an effective myopia control mechanism in European children.

Wei-Han et al18 point out that they did not evaluate the effect of the withdrawal of atropine. Tang et al22 reported on the follow up on the children from the ATOM study children one year of after their cessation of the use of atropine 1%. In the 12- month period the atropine treated eye showed a more rapid myopic progression when compared to the placebo treated eye. Despite this increase in progression the treated eyes still remained less myopic than the placebo treated eye. All children showed a return to normal accommodative responses after the withdrawal of the atropine.

Clearly one of the drawbacks to the use of atropine is the induced loss of accommodation and pupil dilation. Cooper et al23 looked at the dosage of atropine which did not give rise to unwanted symptoms. They concluded that 0.02% atropine met these criteria. The ATOM 2 study24 reported on the use of 0.5%, 0.1%, and 0.01% atropine in the control of myopia. They found that after two years the myopia progression had been -0.30 +/- 0.6, -0.38 +/- 0.6 and -0.49 +/- 0.63 respectively. The group felt the 0.01% drops offered an acceptable level of myopia control without the adverse effects associated with 1% atropine. In 2016 the group reported on a five-year follow up of children recruited to the ATOM2 study.25 After the initial two-year study24 children had ceased use of any of the three percentages of atropine for a 12-month period. Children who showed myopia progression of ≥ -0.50D in that year were recommenced on 0.01% atropine. They concluded that the 0.01% atropine drops had produced the most effective control of myopia without the adverse effects. In the second article in this series we considered the contact lens interventions available for the control of myopia progression. Lin et al compared a group of children treated with overnight orthokeratology with an equivalent group treated with 0.125% atropine over a three-year period.26 They concluded that atropine and orthokeratology produced similar controls on myopic progression.

Studies have also looked at the use of pirenzepine for the control of myopia.27,28 The benefit of pirenzepine is that, as a selective antagonist affecting only the M1 muscarinic receptors, the unwanted effect of mydriasis and cycloplegia are reduced. A 2% gel of pirenzepine administered twice a day for 12 months was an effective myopia control mechanism reducing progression by approximately 50%.

Difficulties arise with both pirenzepine and 0.01% or 0.0125% atropine as they are not commercially available. While 0.5% and 1% atropine are available, use of these drops is restricted in the UK to practitioners with additional prescribing qualifications. Given these restrictions, the use of spectacle interventions seems to be the more acceptable mechanism of the two presented in this article. Concerns also arise regarding the use of potentially harmful drugs on small children. The limited efficacy of the multifocal interventions outlined at the beginning of this article indicate that currently the way forward in our battle with the myopia epidemic probably lies in the use of contact lenses. Review articles for the use of multifocals14 and for the use of atropine29 are available for additional information. 

Dr Annette Parkinson is a senior lecturer at the University of Bradford responsible for the teaching of investigative techniques and visual impairment and rehabilitation.

References

  1. Mutti DO, Jones LA, Moeschberger ML & Zadnik K A/C A Ratio, Age and Refractive Error in Children IOVS 2000; 41: 2,469-2,478.
  2. Gwiazda J, Thorn F & Held R. Accommodation, Accommodative Convergence, and Response AC/A Ratios Before and at the Onset of Myopia in Children, Optom Vis Sci 2005; 82: 273-278.
  3. Gwiazda JE, Hyman L, Norton TT, Hussein MEM, 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. IOVS 2004; 45: 2,143-2,151.
  4. Wick RE. The use of bifocals in myopia – A case report. Am J Optom Arch Am Acad Optom 1947; 24: 368-371.
  5. Goss DA. Effect of Bifocal Lenses on the rate of Childhood Myopia Progression. Am J Ophthal & Phys Opt 1986; 63: 135- 141.
  6. Fulk GW, Cyert LA & Parker DE. A Randomized Trial of Single Vision Lenses vs Bifocal lenses on Myopia Progression in Children with Esophoria. Optom Vis Sci 2000; 77: 395-401.
  7. Cheng D, Woo GC, Drobe B & Schmid KL. Effect of Bifocal and Prismatic Bifocal Spectacles on Myopia Progression in Children, JAMA Ophthalmol 2014; 132: 258-264.
  8. Cheng D, Schmid KL & Woo GC. The effect of positive-lens addition and base-in prism on accommodation accuracy and near horizontal phoria in Chinese myopic children. Ophthalmol & Phys Opt 2008; 28: 225-237.
  9. Leung JTM & Brown B. Progression of Myopia in Hong Kong Schoolchildren is slowed by Wearing Progressive Lenses, OVS 1999; 76: 346-354.
  10. Edwards MH, Li RW, Lam CS, Lew JK & Yu BS. The Hong Kong Progressive Lens Myopia Control Study: Study Design and Main Findings, IOVS 2002; 43: 2,852-2,858.
  11. Correction of Myopia Evaluation Trial 2 Study Group for the Pediatric Eye Disease Investigator Group Progressive-Addition Lenses versus Single-Vision Lenses for Slowing Progressive Myopia in Children with High Accommodative Lag and Near Esophoria. IOVS 2011; 52: 2,749-2,757.
  12. 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. IOVS 2012; 53: 640-649.
  13. Hasebe S, Nakatsuka C, Hamasaki I & Ohtsuki H. Downward deviation of progressive addition lenses in a myopia control trial. Ophthal Physiol Opt 2005; 25: 310-314.
  14. Cheng D, Woo GC & Schmid KL. Bifocal lens control of myopia progression in children. Clin Exp Optom 2011; 94: 24-32.
  15. Tabernero J, Vazquez D, Seidermann A, Uttenweiler D & Schaffel F. Effects of myopic spectacle correction and radial refractive gradient spectacles on peripheral refraction. Vis Res 2009; 49: 2,176-2,186.
  16. Sankaridurg P, Donovan L, Varnas S, Ho A, Chen X, Martinez, A, Fisher S, Liu Z, Smith III EL, Ge J & Holden B. Spectacle Lenses Designed to Reduce Progression of Myopia: 12-Month Results. Optom Vis Sci 2010; 87: 631-641.
  17. Hasebe S, Jun J & Varnas SR. Myopia Control with Positively Aspherized Progressive Addition Lenses: A 2-year Multicenter Randomized Controlled Trial. IOVS 2014; 55: 7,177-7,188.
  18. Wei-Han C, Balakrishnan V, Cnan Y-H, Ling Y, Quah B-L & Tan D. Atropine for the Treatment of Childhood Myopia Ophthalmol 2006; 113: 2,285-2,291.
  19. Yi, S., Huang, Y., Yu, S-Z., Chen, X-J., Yi, H. & Zeng, X-L Therapeutic effect of 1% atropine in Children with Low Myopia. JAAPOS 2015; 19:  426 – 429
  20. Li, S-M., Wu, S-S., Kang, M-T., Liu, Y., Jia, S-M., Li, S-Y., Zhan, S-Y., Liu, L-R., Li, H., Chen, W., Yang, Z., Sun, Y-Y., Wang, N. & Millodot, M. Atropine Slows Myopia Progression More in Asian then White Children by Meta-analysis. Optom Vis Sci 2014; 91: 342 – 350
  21. Polling, J.R., Kok, R.G.W., Tideman, J.W.L., Meskat, B. & Klaver, C.C.W. Effectiveness study of atropine for progressive myopia in Europeans. Eye 2016; 30: 998 - 1004
  22. Tang, L., Huang, X.L., Koh, A.L.T., Zhang, X., Tan, D.T.H. & Chua, W-H Atropine for the Treatment of Childhood Myopia: Effect on Myopia Progression after Cessation of Atropine. Ophthalmology 2009; 116: 572 – 579
  23. Cooper, J., Eisenberg, N., Schulman, E. & Wang, F.M. Maximum Atropine Dose Without Clinical Signs or Symptoms. Optom Vis Sci 2013; 90: 1467 – 1472
  24. Chui, A., Chun, W-H., Cheung, Y-B., Wong, W-L., Lingham, A., Fong, A. & Tan, D. 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 2012; 119: 347 – 354
  25. Chia, A., Lu, Q-S. & Tan, D. Five-Year Clinical Trial on Atropine for the Treatment of Myopia 2 (Myopia Control with Atropine 0.01% Eye drops) Ophthalmology 2016; 123: 391 – 399
  26. Lin, H-J., Wan, L., Tsai, F-J., Tsai, Y-Y., Chen, L-A., Tsai, A.L. & Huang, Y-C Overnight orthokeratology is comparable with atropine in controlling myopia. BMC Ophthalmology 2014; 14: 40
  27. Siatkowski, R.M., Cotter, S., Miller, J.M., Scher, C.A., Stephens Crockett, R. & Novack, G.D. Safety and Efficacy of 2% Pirenzepine Ophthalmic Gel in Children With Myopia A 1-Year, Multicenter, Double-Masked, Placebo-Controlled Parallel Study Arch Ophthalmol. 2004; 122: 1667 – 1674
  28. Tan, D.T.H., Lam, D.S., Chua, W.H., Shu-Ping, D.F. & Stephens Crockett, R.One-Year Multicenter, Double-Masked, Placebo-Controlled, Parallel Safety and Efficacy Study of 2% Pirenzepine Ophthalmic Gel in Children with Myopia. Ophthalmology 2005; 112: 84–91
  29. Shih, K.C., Chan, T. C-Y., Ng, A.L-K., Lai, J.S-M., Li, W.W-T., Cheng, A.C-K. & Fan, D. S-P. Use of Atropine for Prevention of Childhood Myopia Progression in Clinical Practice. Eye & Contact Lens 2016; 42: 16 –23