Pharmaceutical Interventions

Cochrane Systematic Review of Myopia Interventions

March 1, 2020

By Dwight Akerman, OD, MBA, FAAO
Chief Medical Editor, Review of Myopia Management

To assess the effects of interventions on slowing myopia progression in children, researchers included spectacles, contact lenses and pharmaceutical agents in randomized controlled trials published through February 2018. Studies when most participants were older than 18 years at baseline were excluded. They also excluded studies when participants had less than 0.25D spherical equivalent myopia.

The researchers assessed how certain the evidence was for each review finding, factoring in problems such as how the studies were done, the inclusion of very small studies and inconsistent results across studies. They also looked for factors that can make the evidence more certain, including very large effects, and graded each finding as very low, low, moderate or high certainty. The authors found 41 studies of treatments to slow myopia progression which included a total of 6,772 children.

The review found that the following treatments may slow the progression of myopia compared with wearing single-vision spectacles:

  • eye drops, in particular antimuscarinic drugs such as atropine, pirenzepine gel and cyclopentolate (moderate-certainty evidence)
  • multifocal spectacles (either bifocal or progressive addition lenses) (moderate-certainty evidence)
  • bifocal soft contact lenses (low-certainty evidence)
  • orthokeratology contact lenses (moderate-certainty evidence)
  • combinations of eye drops and multifocal spectacles (moderate-certainty evidence)

The review found that the following treatments may have a small effect or no effect on myopia progression:

  • spherical aberration soft contact lenses (low-certainty evidence)
  • systematic adenosine antagonists (moderate-certainty evidence)

Children who wear under-corrected spectacles may have an increased chance of myopia progression compared with children who wear fully corrected spectacles (low-certainty evidence). Only very low-certainty evidence on rigid gas permeable contact lenses (RGPCL) was available.

 

ABSTRACT

Interventions to slow progression of myopia in children

Jeffrey J. Walline, Kristina Lindsley, Satyanarayana S. Vedula, Susan A. Cotter, Donald O. Mutti, Sueko M. Ng and J. Daniel Twelker

BACKGROUND: Nearsightedness (myopia) causes blurry vision when one is looking at distant objects. Interventions to slow the progression of myopia in children include multifocal spectacles, contact lenses and pharmaceutical agents.

OBJECTIVES: To assess the effects of interventions, including spectacles, contact lenses and pharmaceutical agents in slowing myopia progression in children.

SEARCH METHODS: We searched CENTRAL, Ovid MEDLINE, Embase.com, PubMed, the LILACS Database; and two trial registrations up to February 2018. A top-up search was done in February 2019.

SELECTION CRITERIA: We included randomized controlled trials. We excluded studies when most participants were older than 18 years at baseline. We also excluded studies when participants had less than -0.25D spherical equivalent myopia.

DATA COLLECTION AND ANALYSIS: We followed standard Cochrane methods.

RESULTS: We included 41 studies (6,772 participants). Twenty-one studies contributed data to at least one meta-analysis. Interventions included spectacles, contact lenses, pharmaceutical agents and combination treatments. Most studies were conducted in Asia or the U.S. Except one, all studies included children 18 years or younger. Many studies were at high risk of performance and attrition bias. Spectacle lenses: undercorrection of myopia increased myopia progression slightly in two studies; children whose vision was undercorrected progressed on average -0.15D (95 percent confidence interval [CI] -0.29 to 0.00;  n = 142; low-certainty evidence) more than those wearing fully corrected single-vision lenses (SVLs). In one study, axial length increased 0.05 mm (95 percent CI -0.01 to 0.11) more in the undercorrected group than in the fully corrected group (n = 94; low-certainty evidence). Multifocal lenses (bifocal spectacles or progressive addition lenses) yielded a small effect in slowing myopia progression; children wearing multifocal lenses progressed on average 0.14 D (95 percent CI 0.08 to 0.21; n = 1463; moderate-certainty evidence) less than children wearing SVLs. In four studies, axial elongation was less for multifocal lens wearers than for SVL wearers (-0.06 mm, 95 percent CI -0.09 to -0.04; n = 896; moderate-certainty evidence). Three studies evaluating different peripheral plus spectacle lenses versus SVLs reported inconsistent results for refractive error and axial length outcomes (n = 597; low-certainty evidence). Contact lenses: there may be little or no difference between the vision of children wearing bifocal soft contact lenses (SCLs) and children wearing single vision SCLs (mean difference (MD) 0.20D, 95 percent CI -0.06 to 0.47; n = 300; low-certainty evidence). Axial elongation was less for bifocal SCL wearers than for single vision SCL wearers (MD -0.11 mm, 95 percent CI -0.14 to -0.08; n = 300; low-certainty evidence). Two studies investigating rigid gas permeable contact lenses showed inconsistent results in myopia progression; these two studies also found no evidence of a difference in axial elongation (MD 0.02mm, 95 percent CI -0.05 to 0.10; n = 415; very low-certainty evidence). Orthokeratology contact lenses were more effective than SVLs in slowing axial elongation (MD -0.28 mm, 95 percent CI -0.38 to -0.19; n = 106; moderate-certainty evidence). Two studies comparing spherical aberration SCLs with single vision SCLs reported no difference in myopia progression nor axial length (n = 209; low-certainty evidence). Pharmaceutical agents: at one year, children receiving atropine eye drops (3 studies; n = 629), pirenzepine gel (2 studies; n = 326), or cyclopentolate eye drops (1 study; n = 64) showed significantly less myopic progression compared with children receiving placebo: MD 1.00 D (95 percent CI 0.93 to 1.07), 0.31 D (95 percent CI 0.17 to 0.44), and 0.34 (95 percent CI 0.08 to 0.60), respectively (moderate-certainty evidence). Axial elongation was less for children treated with atropine (MD -0.35 mm, 95 percent CI -0.38 to -0.31; n = 502) and pirenzepine (MD -0.13 mm, 95 percent CI -0.14 to -0.12; n = 326) than for those treated with placebo (moderate-certainty evidence) in two studies. Another study showed favorable results for three different doses of atropine eye drops compared with tropicamide eye drops (MD 0.78 D, 95 percent CI 0.49 to 1.07 for 0.1 percent atropine; MD 0.81 D, 95 percent CI 0.57 to 1.05 for 0.25 percent atropine; and MD 1.01 D, 95 percent CI 0.74 to 1.28 for 0.5 percent atropine; n = 196; low-certainty evidence) but did not report axial length. Systemic 7-methylxanthine had little to no effect on myopic progression (MD 0.07 D, 95 percent CI -0.09 to 0.24) nor on axial elongation (MD -0.03 mm, 95 percent CI -0.10 to 0.03) compared with placebo in one study (n = 77; moderate-certainty evidence). One study did not find slowed myopia progression when comparing timolol eye drops with no drops (MD -0.05 D, 95 percent CI -0.21 to 0.11; n = 95; low-certainty evidence). Combinations of interventions: two studies found that children treated with atropine plus multifocal spectacles progressed 0.78 D (95 percent CI 0.54 to 1.02) less than children treated with placebo plus SVLs (n = 191; moderate-certainty evidence). One study reported -0.37 mm (95 percent CI -0.47 to -0.27) axial elongation for atropine and multifocal spectacles when compared with placebo plus SVLs (n = 127; moderate-certainty evidence). Compared with children treated with cyclopentolate plus SVLs, those treated with atropine plus multifocal spectacles progressed 0.36 D less (95 percent CI 0.11 to 0.61; n = 64; moderate-certainty evidence). Bifocal spectacles showed small or negligible effect compared with SVLs plus timolol drops in one study (MD 0.19 D, 95 percent CI 0.06 to 0.32; n = 97; moderate-certainty evidence). One study comparing tropicamide plus bifocal spectacles versus SVLs reported no statistically significant differences between groups without quantitative results. No serious adverse events were reported across all interventions. Participants receiving antimuscarinic topical medications were more likely to experience accommodation difficulties (Risk Ratio [RR] 9.05, 95 percent CI 4.09 to 20.01) and papillae and follicles (RR 3.22, 95 percent CI 2.11 to 4.90) than participants receiving placebo (n=387; moderate-certainty evidence).

CONCLUSIONS: Antimuscarinic topical medication is effective in slowing myopia progression in children. Multifocal lenses, either spectacles or contact lenses, may also confer a small benefit. Orthokeratology contact lenses, although not intended to modify refractive error, were more effective than SVLs in slowing axial elongation. We found only low or very low-certainty evidence to support RGPCLs and spherical aberration SCLs.

Walline, J. J., Lindsley, K. B., Vedula, S. S., Cotter, S. A., Mutti, D. O., Ng, S. M., & Twelker, J. D. (2020). Interventions to slow progression of myopia in children. Cochrane Database of Systematic Reviews, (1).

DOI: 10.1002/14651858.CD004916.pub4

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