Is there a dose response in myopia control?
In this article:
A dose response in medicine is when an outcome of a treatment is influenced by the magnitude of the treatment agent administered.1 In myopia, the concept of a dose-response relationship could relate to the concentration of atropine,2 or the amount and location of myopic defocus in an optical treatment. Animal models so far have indicated that peripheral retinal defocus signals drive eye growth,3 and that the location and amount of lens-induced defocus influences eye growth.4,5 What have we learnt so far in myopia control treatment studies?
The dose-response for atropine has been documented in the LAMP study, where it was shown that the placebo, 0.01%, 0.025% and 0.05% atropine all yielded different myopia control outcomes. In the first year of the study, each atropine concentration showed a significantly different outcome for slowing axial elongation, with better results for stronger concentrations. In the second and third year of the study, 0.01% and 0.025% were no different.2
A dose-response relationship was also shown for ceasing atropine, with 0.05% showing a slightly larger but 'clinically insignificant rebound' of 0.04mm more eye growth over one year. There was not a dose-response with side effects, though, as both 0.025% and 0.05% had similar, minimal effects.2 To learn more about the study, read our article The LAMP Study Data Over Three Years: 0.05% Atropine Leads And Minimally Rebounds.
Soft contact lenses
The only direct comparison of a 'dose' in multifocal soft contact lenses comes from the Bifocal Lenses in Nearsighted Kids (BLINK) study, where the high add power(+2.50D) center-distance multifocal soft contact lenses provided a significant myopia control effect while the medium add power (+1.50D) did not.6 While this may suggest that a higher magnitude of myopic defocus produces higher myopia control efficacy, it only tested two add powers - it could instead indicate that a 'threshold' is reached, with the +2.50D lens changing peripheral refraction and eye length but the +1.50D failing to do so.7
A 'dose' could be described by the optical profile or effective 'add' power of a soft contact lens design. There are few direct comparisons of the optical profiles of different soft multifocal or multi-zone contact lenses used for myopia control, and no direct comparisons of their myopia control efficacy. One study which compared the power profiles of the dual-focus MiSight 1 day, Biofinity center-distance Multifocal and NaturalVue Multifocal (NVMF) found a higher shift in power in the NVMF.8 This was supported by a research abstract which found around double the power shift in the NVMF compared to two center-distance multifocals (Biofinity and Proclear +2.50D add).9
Stepping back to animal models, two chicken studies have shown a dose-response with the NaturalVue Multifocal (NVMF) contact lens design. Two test lenses were investigated, in comparison to single vision - one was the NVMF design and another was a 50% magnitude of the peripheral defocus power in the NVMF ('reduced' NVMF). Both designs managed to reduce or even reverse lens-induced myopia development in chickens, with the largest effect found with the NVMF and a lesser result with the reduced NVMF. The first study showed that development of lens-induced myopia was inhibited by both test lenses, more so with the full NVMF.10 The second study firstly induced myopia in all chicks, and then divided them into the single vision, reduced NVMF or full NVMF test groups. Chickens that received a single vision contact lens progressed as expected. Those chickens that received the full add NVMF achieved reversal of their myopia and became hyperopic. The reduced NVMF group also became less myopic, but to a lesser extent than the full NVMF group.11
Figure 1 from the open access paper Inhibition of Defocus-Induced Myopia in Chickens10 with the following caption: "Mean refractive error ± SE (D) of the treated and untreated eyes of the chickens that completed the study period from the Control group (n = 17), the Test 1 group (n = 14), and the Test 2 group (n = 6). Dashed lines on graph indicate data from untreated, nonlens wearing eyes." Note that the Test 1 lens was the NVMF, showing the least eye growth, and Test 2 was the reduced NVMF.
A large retrospective cohort study of the NVMF lens has indicated a myopia control effect in children, with a subset showing axial elongation of only 0.1mm per year.12 A randomized controlled clinical trial named PROTECT is underway.
The newest design reported is described with “concentric, annular zones with +7 D non-coaxial plus power [and] a +10 D co-axial treatment zone… to further “boost” myopia control efficacy.” This lens has not yet been power profiled in comparison to other designs, but six-month efficacy results show a larger response when compared to a ‘standard dual-focus design', although the add power of the latter was not specified. Further longitudinal studies are underway.13
Taken in total, the animal studies give indication of a dose-response in multifocal and multi-zone soft contact lenses. Human studies aren’t yet conclusive, but there are some indications - more needs to be learnt about the impact of lens configuration (aspheric, concentric or other) as well as comparative power profiles.
It is difficult to alter the 'power profile' of an orthokeratology (ortho-k) lens as for soft contact lens designs, but one study has evaluated "orthokeratology with increased compression factor (OKIC)" of an additional 1.00D target central flattening. The OKIC lenses showed a 34% (0.18mm) better myopia control effect over two years than "conventional compression factor" ortho-k lenses.14 Topography results showed similar central flattening but more mid-peripheral steepening in the OKIC lenses, and more higher order aberrations were also reported,15 but no direct correlations between an increased 'dose' of topographical steepening or higher order aberrations and the myopia control effect has been reported.
A study investigating highly aspherical lenslets (HAL), slightly aspherical lenslets (SAL) and single vision spectacle lenses found a dose-dependent response over two years, with the HAL lens being most effective. The 'dose' of wearing time was also significant, with the best results found for children who wore their HAL spectacle lenses for at least 12 hours per day, 7 days per week.16
Time spent outdoors
A dose-dependent response with increased outdoor time and reduced myopia prevalence and progression has been reported, with the threshold being 120 minutes per day.17
Is there a dose-response in myopia control?
There is certainly a volume of evidence from animal models, and some evidence in human studies too. A dose-response relationship is clear for atropine and time spent outdoors. For optical treatments, though, it is more difficult to conclusively evaluate due to the limited data points available - we may be seeing a 'threshold' being cleared for the myopia control effect, more so than a direct dose-response relationship. There is lots more to learn in this arena.
Meet the Authors:
About Kate Gifford
Dr Kate Gifford is a clinical optometrist, researcher, peer educator and professional leader from Brisbane, Australia, and a co-founder of Myopia Profile.
About Jeanne Saw
Jeanne is a clinical optometrist based in Sydney, Australia. She has worked as a research assistant with leading vision scientists, and has a keen interest in myopia control and professional education.
Read Jeanne's work in the CLINICAL domain of MyopiaProfile.com. Jeanne also writes for our My Kids Vision website, our public awareness platform, and supports development of new resources across our platforms.
This content is brought to you thanks to unrestricted educational grant from
- Pettygrove, Sydney. "dose-response relationship". Encyclopedia Britannica, 23 Sep. 2016, https://www.britannica.com/science/dose-response-relationship. Accessed 23 November 2022.
- Yam JC, Zhang XJ, Zhang Y, Wang YM, Tang SM, Li FF, Kam KW, Ko ST, Yip BHK, Young AL, Tham CC, Chen LJ, Pang CP. Three-Year Clinical Trial of Low-Concentration Atropine for Myopia Progression (LAMP) Study: Continued Versus Washout: Phase 3 Report. Ophthalmology. 2022 Mar;129(3):308-321. (link) [Link to Myopia Profile Science Summary]
- Smith EL 3rd. Prentice Award Lecture 2010: A case for peripheral optical treatment strategies for myopia. Optom Vis Sci. 2011 Sep;88(9):1029-44. (link)
- Smith Iii EL, Arumugam B, Hung LF, She Z, Beach K, Sankaridurg P. Eccentricity-dependent effects of simultaneous competing defocus on emmetropization in infant rhesus monkeys. Vision Res. 2020 Dec;177:32-40. (link)
- Troilo D, Smith EL 3rd, Nickla DL, Ashby R, Tkatchenko AV, Ostrin LA, Gawne TJ, Pardue MT, Summers JA, Kee CS, Schroedl F, Wahl S, Jones L. IMI - Report on Experimental Models of Emmetropization and Myopia. Invest Ophthalmol Vis Sci. 2019 Feb 28;60(3):M31-M88. (link)
- Walline JJ, Walker MK, Mutti DO, et al. Effect of High Add Power, Medium Add Power, or Single-Vision Contact Lenses on Myopia Progression in Children. JAMA. 2020;324(6):571-580. (link) [Link to Myopia Profile Science Review]
- Mutti DO, Sinnott LT, Berntsen DA, Jones-Jordan LA, Orr DJ, Walline JJ; BLINK Study Group. The Effect of Multifocal Soft Contact Lens Wear on Axial and Peripheral Eye Elongation in the BLINK Study. Invest Ophthalmol Vis Sci. 2022 Sep 1;63(10):17. (link) [Link to Myopia Profile Science Summary]
- Sah RP, Jaskulski M, Kollbaum PS. Modelling the refractive and imaging impact of multi-zone lenses utilised for myopia control in children's eyes. Ophthalmic Physiol Opt. 2022 May;42(3):571-585. (link) [Link to Myopia Profile Science Summary]
- Nyarko Nti A, Ritchey ER, Berntsen DA. Power profiles of center-distance multifocal soft contact lenses. Invest Ophthalmol Vis Sci. 2020;61:1180. (link)
- Woods J, Guthrie SE, Keir N, Dillehay S, Tyson M, Griffin R, Choh V, Fonn D, Jones L, Irving E. Inhibition of defocus-induced myopia in chickens. Invest Ophthalmol Vis Sci. 2013 Apr 12;54(4):2662-8.(link)
- Irving EL, Yakobchuk-Stanger C. Myopia progression control lens reverses induced myopia in chicks. Ophthalmic Physiol Opt. 2017 Sep;37(5):576-584. (link)
- Cooper J, O'Connor B, Aller T, Dillehay SM, Weibel K, Benoit D. Reduction of Myopic Progression Using a Multifocal Soft Contact Lens: A Retrospective Cohort Study. Clin Ophthalmol. 2022 Jul 4;16:2145-2155. (link)
- Cheng X, Xu J, Brennan NA. Randomized trial of soft contact lenses with novel ring focus for controlling myopia progression. Ophthalmol Sci 2022:Oct 18. (link) [Link to Myopia Profile Science Summary]
- Lau JK, Wan K, Cho P. Orthokeratology lenses with increased compression factor (OKIC): A 2-year longitudinal clinical trial for myopia control. Cont Lens Anterior Eye. 2022 Aug 19:101745. (link)
- Lau JK, Vincent SJ, Cheung SW, Cho P. The influence of orthokeratology compression factor on ocular higher-order aberrations. Clin Exp Optom. 2020 Jan;103(1):123-128. (link)
- Bao J, Huang Y, Li X, Yang A, Zhou F, Wu J, Wang C, Li Y, Lim EW, Spiegel DP, Drobe B, Chen H. Spectacle Lenses With Aspherical Lenslets for Myopia Control vs Single-Vision Spectacle Lenses: A Randomized Clinical Trial. JAMA Ophthalmol. 2022 May 1;140(5):472-478. (link) [Link to Myopia Profile Science Summary]
- Ho CL, Wu WF, Liou YM. Dose-Response Relationship of Outdoor Exposure and Myopia Indicators: A Systematic Review and Meta-Analysis of Various Research Methods. Int J Environ Res Public Health. 2019 Jul 21;16(14):2595. (link)
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