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HomemieyecareAtropine – Efficacy & Possible Mechanisms for Myopia Control

Atropine – Efficacy & Possible Mechanisms for Myopia Control

There is increasing evidence to warrant atropine’s use for myopia control, however more research is needed to fully understand its exact mechanism.

A large number of investigative studies, relating to the efficacy and possible mechanisms of myopia control interventions, were presented at this year’s International Myopia Conference (IMC) in Birmingham. Of the various myopia control methods, atropine – a nonspecific muscarinic receptor antagonist – remains the most effective treatment for myopia. Atropine is commercially available as 1 per cent topical eye drops and is associated with adverse side effects, such as glare, photophobia and blurring of near vision, which have limited its clinical use. However, these side effects are dose-dependent, and are greatly reduced with lower concentrations, which surprisingly do not have a corresponding decrease in atropine’s myopia control efficacy.1 Recent meta-analyses have shown atropine’s potency with an effect size of 0.68D/year reduction in myopia at 1 per cent strength when compared with single vision spectacle lenses or placebo, and still 0.53D/year reduction at concentrations as low as 0.01 per cent.2 In addition to fewer side effects, rebound effects (i.e. acceleration of myopia progression when ceasing atropine) are reduced with the use of lower concentrations.3

Combined Atropine and Optical Treatment

Although the universal use of atropine for myopia control still remains low, the use of atropine as a first line treatment for slowing myopia progression in children is now common in several East Asian countries, such as Taiwan. While atropine is the most effective tool for reducing myopia progression, it does not offer complete control. One way to increase the efficacy of atropine in reducing myopia progression would be to combine it with optical methods of myopia control, such as Orthokeratology and Dual-Focus lenses. An early indication of an additive effect was presented by John Phillips, who investigated the effect of simultaneous optical defocus and 0.3 per cent atropine on subfoveal choroidal thickness – a biomarker for predicting myopia progression.4 They found that myopic defocus resulted in an additional increase in choroidal thickness, which had already been increased by atropine over a period of six months. This suggests that combining atropine with optical therapy may provide more effective myopia control, although how atropine acts to control myopia remains unknown.

Several studies presented at the IMC attempted to address this gap. A study from The University of Auckland Myopia Laboratory investigated the response of 0.1 per cent atropine to human multifocal electroretinography responses (amplitudes) under the various magnitudes of defocus: myopic, hyperopic, and no defocus.5 They found that atropine acted in a sign-dependent manner, enhancing mfERG responses to myopic defocus, without affecting the response to hyperopic defocus. Furthermore, this differential effect of atropine was evident only at the inner retinal level and in the peripheral retina, suggesting the peripheral inner retina might predominantly mediate inhibition of myopia by atropine.

One way to increase the efficacy of atropine in reducing myopia progression would be to combine it with optical methods of myopia control

This finding was supported in a chick model of myopia, where researchers from the same lab presented a novel immunohistochemistry protocol showing that atropine tended to accumulate in the inner retina.6 In another study by The Schaeffel lab from The University of Tübingen, intravitreal injection of atropine in chick eyes did not change pupillary responses, despite an atropine-induced increase in dopamine levels.7 This suggests that atropine might not influence the retinal adaptational state, but because atropine stimulates dopamine release, the authors speculated that atropine might represent a light signal for the retina and therefore inhibit myopia by mimicking exposure to bright light.

More Research Required

Although we have come a long way in understanding atropine eye drops as an effective treatment for myopia, and its clinical use is increasing worldwide, the exact mechanism still remains unclear. Furthermore, there are still issues regarding the clinical use of atropine for myopia control, in particular, its long term effects and predicting those who respond best to treatment. Additionally, the best approach (dose, regime, and concentration for optimal effect) is yet to be fully established. For example, work from U.C. Berkeley8 showed similar effects on both accommodation and pupil size after either daily or every second day dosing of low-dose atropine, suggesting that the effects of atropine may persist for long enough to permit a reduced dosing schedule – but the effect on myopia control will need to be investigated.

While there are still gaps in our understanding of how atropine reduces myopia progression, the literature is sufficient to warrant atropine’s use for myopia control – especially given the looming threat of the ‘myopia boom’.

Safal Khanal, OD, FAAO is a PhD candidate in the School of Optometry and Vision Sciences Myopia Laboratory at the University of Auckland. He is currently investigating the mechanism by which optical and pharmacological interventions act to control myopia, using electrophysiology and perfusion MRI methods. He is also a clinical fellow of the American Academy of Optometry and a research member of the Myopia Control Clinic at the University of Auckland.

Philip Turnbull, BOptom (Hons), PhD, holds both lecturer and research fellow positionsin the School of Optometry and Vision Science at The University of Auckland. His PhD showed emmetropisation in the convergently evolved cephalopod eye. He also served as the Director of the Myopia Control Clinic at The University of Auckland

References
1. Gong Q, Janowski M, Luo M, Wei H, Chen B, Yang G, et al. Efficacy and Adverse Effects of Atropine in Childhood Myopia: A Meta-analysis. JAMA Ophthalmol. 2017 Jun 1;135(6):624–30.
2. Huang J, Wen D, Wang Q, McAlinden C, Flitcroft I, Chen H, et al. Efficacy Comparison of 16 Interventions for Myopia Control in Children: A Network Meta-analysis. Ophthalmology. 2016 Apr;123(4):697–708.
3. 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% Eyedrops. Ophthalmology. 2016 Feb;123(2):391–9.
4. Chiang S, Turnbull P, Phillips J. Interaction of atropine and retinal image defocus on choroidal thickness in children with myopia. Paper presented at 16th International Myopia Conference. 2017 September, Birmingham, UK.
5. Lee N, Khanal S, Turnbull P, Phillips J. Effect of Atropine on Human Multifocal Electroretinogram Responses to Defocus. Poster presented at 16th International Myopia Conference. 2017 September, Birmingham, UK.
6. Yeoman J, Collins A, Phillips J. Atropine Immunolocalisation in Form-deprived Chick Eyes. Poster presented at 16th International Myopia Conference. 2017 September, Birmingham, UK.
7. Mathis U, Feldkaemper M, Wang M, Schaeffel F. Effect of Intravitreal Atropine on Dopamine Release and Pupil Responses in Chickens. Poster presented at 16th International Myopia Conference. 2017 September, Birmingham, UK.
8. Kochik S. Atropine Dosing Frequency. Paper presented at 16th International Myopia Conference. 2017 September, Birmingham, UK.