The University of Manchester Research How effective are atropine eye drops at reducing myopia progression in children? Document Version Final published version Link to publication record in Manchester Research Explorer Citation for published version (APA): Jinabhai, A., & Glover, M. (2019). How effective are atropine eye drops at reducing myopia progression in children? Optometry in Practice (OiP), 20(3), 1-18. [EV-59579 C-72220]. https://www.college-optometrists.org/oip- resource/atropine-eye-drops-to-control-myopia-progression.html Published in: Optometry in Practice (OiP) Citing this paper Please note that where the full-text provided on Manchester Research Explorer is the Author Accepted Manuscript or Proof version this may differ from the final Published version. If citing, it is advised that you check and use the publisher's definitive version. 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Amit Navin Jinabhai PhD BSc(Hons) MCOptom FBCLA FHEA FEAOO and Mark Glover BSc(Hons) MCOptom The University of Manchester, Faculty of Biology Medicine and Health, School of Health Sciences, Division of Pharmacy and Optometry EV-59579 C-72220 1 CET point for UK optometrists Abstract Myopia is a global problem which typically shows the highest prevalence in the Far East. As the number of myopes continues to grow, worldwide, the incidence of myopia-related ocular pathology is also likely to increase. In a targeted attempt to reduce these pathologies, a range of different types of clinical interventions have been designed and administered in order to try and inhibit myopia progression in children, including the use of pharmaceutical agents such as atropine. To date, atropine has predominantly been used in studies conducted in the Far East, where it has mainly been used in an ‘off-label’ capacity. This review paper discusses the relative strengths and weaknesses of peer-reviewed, scientific research studies investigating the efficacy of atropine, in varying concentrations, at regressing myopia progression in children. A critical appraisal of the literature is needed in order to better understand key issues with regard to the clinical administration of atropine, such as the optimum concentration to use; the optimal refractive error at which to start treatment; the longevity of the effect(s); what possible side-effects could occur; the importance of compliance with the treatment regimen, and whether atropine could be considered for use in combination with other established interventions (such as orthokeratology). Although atropine is not yet readily available to use for the treatment of myopia progression in the UK, practising optometrists would benefit from gaining a better understanding of the efficacy of this treatment and its limitations, in the anticipation that this drug is adopted for wider clinical use, in a low concentration, in the near future. Introduction Due to its multifactorial and complex nature, the process(es) of and reason(s) for myopic progression are still, currently, Myopia is a global problem,1–12 particularly in Far East unclear.18,42 Animal models indicate causative effects Asia,1,6,8,9,12,13 where the prevalence is approximately such as form deprivation,43 relative peripheral hyperopic 80% amongst young adults in Taiwan8 and around 80% defocus44 and biological feedback-loop interruption.18 amongst Chinese, young adult males in Singapore.14 Conversely, Myopia progression may also be influenced by genetics,45 time amongst European young adults, the prevalence varies spent outdoors,46–49 performing intense periods of near-work between 25% and 50%.10 Myopia is a key cause of preventable tasks50,51 and accommodative lag.52,53 However, precisely blindness and can lead to serious ocular complications, how each of these factors might work together is still such as glaucoma, choroidal neovascularisation and retinal controversial and largely unclear. detachment.15–17 Before the age of 6 years, most children are usually hyperopic, Atropine with a smaller proportion being either emmetropic or myopic. Atropine is a non-selective, competitive muscarinic Typically, around the age of 7 years, some children undergo acetylcholine receptor antagonist, with a high affinity for a marked shift in refractive error, resulting in manifest all five forms of muscarinic receptors (i.e. M1–M554) located myopia; this abrupt shift is often referred to as ‘myopia within the eye (particularly those in the sclera and retina55–57), progression’.13,15,18 A targeted reduction in the severity of which cause both cycloplegia and mydriasis.58 Atropine this ‘myopic shift’ has been the subject of a wide range of has been routinely used (off-label) in approximately 50% of research strategies (summarised in Figure 1), including: the paediatric myopic progression cases in Taiwan since 2007.59 use of rigid gas-permeable lenses19; orthokeratology contact Despite this popularity, atropine is not currently approved lenses20–26; bifocal or multifocal soft contact lenses27–31; for myopia control by the US Food and Drug Administration bifocal or multifocal spectacle lenses32–35; and ophthalmic (FDA),60 nor is it approved for myopia control in the UK. drugs such as atropine36–38 or pirenzepine.39–41 With a growing body of evidence indicating that Date of acceptance: 4 July 2019. [email protected] © 2019 The College of Optometrists 1 A Jinabhai and M Glover How effective are atropine eye drops at reducing myopia progression in children? low-concentration atropine might be effective at reducing the recipients were myopic children. Studies which did not Figure 1. Summary of different myopia progression, the likelihood of its more global use, meet these criteria were not reviewed; for example, studies myopia control strategies used particularly in the west, also increases. This paper aims to that used atropine ointment were not included as part of in child patients from peer- critically review research studies conducted to reduce myopia this review. We were particularly interested in exploring reviewed scientific research progression in children, using atropine eye drops. differences in study designs between various research studies. ATOM, Atropine for investigations. the Treatment Of Myopia; For ease of comparison, Table 1 summarises some of the key CRAYON, Corneal Reshaping studies reviewed in this paper, whilst Table 2 presents a critical And Yearly Observation of Clinical measurements and study design list of key limitations for the same group of studies. Near-sightedness; LORIC, for assessing myopia progression Longitudinal Orthokeratology Compared to non-myopes, myopes tend to have longer The search engine PubMed was used to search for studies Research In Children; RGP, axial lengths, deeper vitreous chambers and flatter using the keywords ‘atropine’ and ‘myopia’. Studies that were rigid gas-permeable; ROMIO, corneas.61,62 In the majority of cases, the primary structural not published in English were excluded. Abstracts of the Retardation Of Myopia In cause of myopia is a long axial length, therefore axial length remaining studies were reviewed to confirm that atropine eye Orthokeratology. is recognised as a key determinant of refractive error.10 drops had been administered as part of the methods and that Subsequently, myopia control studies typically focus on slowing down axial elongation, thereby progressively reducing the rate of myopisation. Measurements of changes in axial length (either via amplitude scan ultrasonography or by Table 1. Summary of research studies evaluating the use of atropine for the control of progressive myopia in child patients partial coherence interferometry (PCI)) are fundamental Authors Number of Study design Participant age Baseline refractive error range (SE in D) Study duration Atropine Control Myopia progression rate to evaluating the efficacy of myopia control treatments. subjects range (years) (years) treatment (%) Treatment group (D/year) Control receiving However, it is worth noting that a number of atropine studies group unfortunately did not measure this key parameter (discussed atropine (D/year) treatment later in this article). Shih et al.86 137 RCT, NM 6 to 13 0.50% group mean: –4.89 ± 2.06; 2 0.50, n=41 0.50% –0.04 ± 0.63 –1.06 ± 0.61 0.25% group mean: –4.24 ± 1.74; 0.25, n=47 Tropicamide –0.45 ± 0.55 A cycloplegic refraction, usually through autorefraction 0.10% group mean: –4.41 ± 1.47; control group mean: –4.50 ± 1.86 0.10, n=49 –0.47 ± 0.91 (however, retinoscopy could be considered to be more 63 Shih et al.90 66 RCT (+DB?) 6 to 13 Tx group mean: –3.20 ± 0.14; 1.5 0.50 PALs + placebo –0.28 –0.79 (PALs) suitable for less cooperative children ), is also essential to PALs+placebo group mean: –3.34 ± 0.14; exclude cases of ‘pseudomyopia’. Additionally, Zadnik and SVS+placebo group mean: –3.28 ± 0.13 SVS + placebo