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The acute effect of atropine eye drops on the human full-field electroretinogram

Abstract

Purpose

Atropine eye drops are a common and effective treatment for slowing myopia progression, but the site and mode of action of atropine in controlling myopia are unclear. We investigated the early retinal sites of action of atropine by examining its effects on the human full-field electroretinogram (ffERG).

Method

Baseline ffERGs were recorded in both eyes of 24 healthy subjects (mean ± SD: 21.0 ± 2.3 years; spherical equivalent refraction, range: + 1.63 to − 0.75 D) using 6 standard ISCEV protocols, 30 min after bilateral pupil dilation with 1% Tropicamide. Atropine (1 drop, 0.1%) was then instilled into the non-dominant eye. 24 h later, ffERGs were again recorded in both eyes. Ratios (post-atropine: pre-atropine) of dark-adapted (DA) and light-adapted (LA) ffERGs were compared between atropine-treated and control eyes using multivariate repeated measures general linear models.

Results

Atropine-treated eyes responded with 14% lower DA3.0 OP (oscillatory potential) amplitude (p = 0.003) and 4% delay in the DA10.0 a-wave peak time (p = 0.00099) compared with control eyes. Amplitudes and peak times were not different between atropine-treated and control eyes for DA0.01, LA3.0, and LA3.0 flicker ERGs. While atropine caused a small (1.26 mm2, p = 0.03) extra increase in pupil area in the treated eye, atropine-induced changes in ffERG responses bore no relationship with changes in pupil area (R2= 2–5%, p > 0.05).

Conclusions

The observed changes in oscillatory potentials corroborate previous findings that atropine affects neural activity in the inner retina. However, observed changes to the a-wave suggest that atropine also affects activity in photoreceptors.

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References

  1. Holden BA, Fricke TR, Wilson DA et al (2016) Global prevalence of myopia and high myopia and temporal trends from 2000 through 2050. Ophthalmology 123:1036–1042

    PubMed  Google Scholar 

  2. Flitcroft DI (2012) The complex interactions of retinal, optical and environmental factors in myopia aetiology. Prog Retin Eye Res 31:622–660

    CAS  PubMed  Google Scholar 

  3. Ohno-Matsui K, Lai TYY, Lai C-C, Cheung CMG (2016) Updates of pathologic myopia. Prog Retin Eye Res 52:156–187

    PubMed  Google Scholar 

  4. Ma X, Zhou Z, Yi H et al (2014) Effect of providing free glasses on children’s educational outcomes in China: cluster randomized controlled trial. BMJ 349:g5740

    PubMed  PubMed Central  Google Scholar 

  5. Smith TST, Frick KD, Holden BA et al (2009) Potential lost productivity resulting from the global burden of uncorrected refractive error. Bull World Health Organ 87:431–437

    CAS  PubMed  PubMed Central  Google Scholar 

  6. Wu P-C, Chen C-T, Lin K-K et al (2018) Myopia prevention and outdoor light intensity in a school-based cluster randomized trial. Ophthalmology 125:1239–1250

    PubMed  Google Scholar 

  7. He X, Sankaridurg P, Xiong S et al (2019) Shanghai time outside to reduce myopia trial: design and baseline data. Clin Experiment Ophthalmol 47:171–178

    PubMed  Google Scholar 

  8. Yam JC, Jiang Y, Tang SM et al (2019) Low-concentration atropine for myopia progression (LAMP) study: a randomized, double-blinded, placebo-controlled trial of 0.05%, 0.025%, and 0.01% atropine eye drops in myopia control. Ophthalmology 126:113–124

    PubMed  Google Scholar 

  9. Chamberlain P, Peixoto-de-Matos SC, Logan NS et al (2019) A 3-year randomized clinical trial of misight lenses for myopia control. Optom Vis Sci 96:556–567

    PubMed  Google Scholar 

  10. Brennan NA (2012) Predicted reduction in high myopia for various degrees of myopia control. Cont Lens Anterior Eye 35:e14–e15

    Google Scholar 

  11. Bullimore MA, Brennan NA (2019) Myopia control: why each diopter matters. Optom Vis Sci 96:463–465

    PubMed  Google Scholar 

  12. Chia A, Chua WH, Cheung YB et al (2012) 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 119:347–354

    PubMed  Google Scholar 

  13. Huang J, Wen D, Wang Q et al (2016) Efficacy comparison of 16 interventions for myopia control in children: a network meta-analysis. Ophthalmology 123:697–708

    PubMed  Google Scholar 

  14. Chia A, Lu Q-SS, Tan DTH (2016) Five-Year clinical trial on atropine for the treatment of myopia 2 myopia control with atropine 0.01% eyedrops. Ophthalmology 123:391–399

    PubMed  Google Scholar 

  15. Stone RA, Lin T, Laties AM (1991) Muscarinic antagonist effects on experimental chick myopia. Exp Eye Res 52:755–758

    CAS  PubMed  Google Scholar 

  16. Schwahn HN, Kaymak H, Schaeffel F (2000) Effects of atropine on refractive development, dopamine release, and slow retinal potentials in the chick. Vis Neurosci 17:165–176

    CAS  PubMed  Google Scholar 

  17. Carr BJ, Stell WK (2016) Nitric oxide (NO) mediates the inhibition of form-deprivation myopia by atropine in chicks. Sci Rep 6:9

    PubMed  PubMed Central  Google Scholar 

  18. Barathi VA, Chaurasia SS, Poidinger M et al (2014) Involvement of GABA transporters in atropine-treated myopic retina as revealed by iTRAQ quantitative proteomics. J Proteome Res 13:4647–4658

    CAS  PubMed  PubMed Central  Google Scholar 

  19. Fischer AJ, Miethke P, Morgan IG, Stell WK (1998) Cholinergic amacrine cells are not required for the progression and atropine-mediated suppression of form-deprivation myopia. Brain Res 794:48–60

    CAS  PubMed  Google Scholar 

  20. Gallego P, Martínez-García C, Pérez-Merino P et al (2012) Scleral changes induced by atropine in chicks as an experimental model of myopia. Ophthalmic Physiol Opt 32:478–484

    PubMed  Google Scholar 

  21. Lind GJ, Chew SJ, Marzani D, Wallman J (1998) Muscarinic acetylcholine receptor antagonists inhibit chick scleral chondrocytes. Invest Ophthalmol Vis Sci 39:2217–2231

    CAS  PubMed  Google Scholar 

  22. Carr BJ, Mihara K, Ramachandran R et al (2018) Myopia-inhibiting concentrations of muscarinic receptor antagonists block activation of alpha2a-adrenoceptors in vitro. Invest Ophthalmol Vis Sci 59:2778–2791

    CAS  PubMed  Google Scholar 

  23. Zhang Z, Zhou Y, Xie Z et al (2016) The effect of topical atropine on the choroidal thickness of healthy children. Sci Rep 6:34936

    CAS  PubMed  PubMed Central  Google Scholar 

  24. Chiang STH, Phillips JR (2018) Effect of atropine eye drops on choroidal thinning induced by hyperopic retinal defocus. J Ophthalmol 2018:1–6

    Google Scholar 

  25. Robson AG, Nilsson J, Li S et al (2018) ISCEV guide to visual electrodiagnostic procedures. Doc Ophthalmol 136:1–26

    PubMed  PubMed Central  Google Scholar 

  26. Khanal S, Turnbull PRK, Lee N, Phillips JR (2019) The effect of atropine on human global flash mfERG responses to retinal defocus. Invest Ophthalmol Vis Sci 60:218–225

    CAS  PubMed  Google Scholar 

  27. McCulloch DL, Marmor MF, Brigell MG et al (2015) ISCEV Standard for full-field clinical electroretinography (2015 update). Doc Ophthalmol 130:1–12

    PubMed  Google Scholar 

  28. Hamilton R, Al Abdlseaed A, Healey J et al (2015) Multi-centre variability of ISCEV standard ERGs in two normal adults. Doc Ophthalmol 130:83–101

    CAS  PubMed  Google Scholar 

  29. Anders LM, Heinrich SP, Lagrèze WA, Joachimsen L (2019) Little effect of 0. 01% atropine eye drops as used in myopia prevention on the pattern electroretinogram. Doc Ophthalmol 138(2):1–11

    Google Scholar 

  30. Wachtmeister L (1998) Oscillatory potentials in the retina: what do they reveal. Prog Retin Eye Res 17:485–521

    CAS  PubMed  Google Scholar 

  31. Heynen H, Van Norren D (1985) Origin of the electroretinogram in the intact macaque eye—II: Current source-density analysis. Vision Res 25:709–715

    CAS  PubMed  Google Scholar 

  32. Zhong X, Ge J, Smith EL, Stell WK (2004) Image defocus modulates activity of bipolar and amacrine cells in macaque retina. Invest Ophthalmol Vis Sci 45:2065–2074

    PubMed  Google Scholar 

  33. Fischer AJ, McGuire JJ, Schaeffel F, Stell WK (1999) Light- and focus-dependent expression of the transcription factor ZENK in the chick retina. Nat Neurosci 2:706–712

    CAS  PubMed  Google Scholar 

  34. Guo SS, Sivak JG, Callender MG, Diehl-Jones B (1995) Retinal dopamine and Lens-induced refractive errors in chicks. Curr Eye Res 14:385–389

    CAS  PubMed  Google Scholar 

  35. Mani A, Schwartz GW, Toda H et al (2017) Circuit mechanisms of a retinal ganglion cell with stimulus-dependent response latency and activation beyond its dendrites. Curr Biol 27:471–482

    CAS  PubMed  PubMed Central  Google Scholar 

  36. Ho WC, Wong OY, Chan YC et al (2012) Sign-dependent changes in retinal electrical activity with positive and negative defocus in the human eye. Vision Res 52:47–53

    PubMed  Google Scholar 

  37. Shimada Y, Bearse MA, Sutter EE (2005) Multifocal electroretinograms combined with periodic flashes: Direct responses and induced components. Graefes Arch Clin Exp Ophthalmol 243:132–141

    PubMed  Google Scholar 

  38. Feldkaemper MP, Schaeffel F (2013) An updated view on the role of dopamine in myopia. Exp Eye Res 114:106–119

    CAS  PubMed  Google Scholar 

  39. Stone RA, Lin T, Laties AM, Iuvone PM (1989) Retinal dopamine and form-deprivation myopia. Neurobiology 86:704–706

    CAS  Google Scholar 

  40. Miller RF, Dacheux RF, Frumkes TE (1977) Amacrine cells in necturus retina: evidence for independent gamma-aminobutyric acid-and glycine-releasing neurons. Science 198:748–750

    CAS  PubMed  Google Scholar 

  41. Wachtmeister L, Dowling JE (1978) The oscillatory potentials of the mudpuppy retina. Invest Ophthalmol Vis Sci 17:1176–1188

    CAS  PubMed  Google Scholar 

  42. Wachtmeister L (1980) Further studies of the chemical sensitivity of the oscillatory potentials of the electroretinogram (ERG) I. GABA-and glycine antagonists Acta Ophthalmol 58:712–725

    CAS  Google Scholar 

  43. Stone RA, Laties AM, Raviola E, Wiesel TN (1988) Increase in retinal vasoactive intestinal polypeptide after eyelid fusion in primates. Proc Natl Acad Sci U S A 85:257–260

    CAS  PubMed  PubMed Central  Google Scholar 

  44. Pickett Seltner RL, Stell WK (1995) The effect of vasoactive intestinal peptide on development of form deprivation myopia in the chick: a pharmacological and immunocytochemical study. Vision Res 35:1265–1270

    Google Scholar 

  45. Zhou X, Pardue MT, Iuvone PM, Qu J (2017) Dopamine signaling and myopia development: what are the key challenges. Prog Retin Eye Res 61:60–71

    CAS  PubMed  PubMed Central  Google Scholar 

  46. Granit R (1933) The components of the retinal action potential in mammals and their relation to the discharge in the optic nerve. J Physiol 77:207–239

    CAS  PubMed  PubMed Central  Google Scholar 

  47. Penn RD, Hagins WA (1969) Signal transmission along retinal rods and the origin of the electroretinographic a-wave. Nature 223:201–204

    CAS  PubMed  Google Scholar 

  48. Robson JG, Frishman LJ (2014) The rod-driven a-wave of the dark-adapted mammalian electroretinogram. Prog Retin Eye Res 39:1–22

    PubMed  Google Scholar 

  49. Chia A, Li W, Tan D, Luu CD (2013) Full-field electroretinogram findings in children in the atropine treatment for myopia (ATOM2) study. Doc Ophthalmol 126:177–186

    PubMed  Google Scholar 

  50. Luu CD, Lau AMI, Koh AHC, Tan D (2005) Multifocal electroretinogram in children on atropine treatment for myopia. Br J Ophthalmol 89:151–153

    CAS  PubMed  PubMed Central  Google Scholar 

  51. Crewther DP (2000) The role of photoreceptors in the control of refractive state. Prog Retin Eye Res 19:421–457

    CAS  PubMed  Google Scholar 

  52. Rucker FJ (2013) The role of luminance and chromatic cues in emmetropisation. Ophthalmic Physiol Opt 33:196–214

    PubMed  Google Scholar 

  53. Liang H, Crewther DP, Crewther SG, Barila AM (1995) A role for photoreceptor outer segments in the induction of deprivation myopia. Vision Res 35:1217–1225

    CAS  PubMed  Google Scholar 

  54. Norton TT, Amedo AO, Siegwart JT (2006) Darkness causes myopia in visually experienced tree shrews. Investigative Opthalmol Visual Sci 47:4700

    Google Scholar 

  55. Wang Y, Xu Y, Liu X et al (2018) Amblyopia, strabismus and refractive errors in congenital ptosis: a systematic review and meta-analysis. Sci Rep 8:8320

    PubMed  PubMed Central  Google Scholar 

  56. He W, Sun T, Yang J et al (2017) Analysis of factors associated with the ocular features of congenital cataract children in the shanghai pediatric cataract study. J Ophthalmol 2017:8647435

    PubMed  PubMed Central  Google Scholar 

  57. Morgan IG, Boelen MK (1996) A retinal dark-light switch: a review of the evidence. Vis Neurosci 13:399–409

    CAS  PubMed  Google Scholar 

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Acknowledgements

The authors thank the New Zealand Association of Optometrists for a Higher Degree Research Write-up Scholarship to SK

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

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Authors and Affiliations

Authors

Contributions

Safal Khanal’s contributions included Conceptualization, Methodology, Formal analysis, Visualisation, Writing – Original Draft. Sachi Rathod’s contributions included Investigation, Data Curation, Project Administration. John Phillips’ contributions included Conceptualization, Supervision, Resources, Writing – Review and Editing.

Corresponding author

Correspondence to John R. Phillips.

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The authors declare that they have no conflict of interest or commercial relationship in relation to this work.

Consent to participate

Written informed consent was obtained from all individual participants included in the study.

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The authors affirm that all participants provided informed consent for publication of the study findings. The study does not report identifying information for any participants.

Statement of human rights

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. The study was approved by the Human Participants Ethics Committee of the University of Auckland (ref: 017982).

Statement on the welfare of animals

No animals were used in this research.

Disclosure

This study was presented in part at the 17th International Myopia Conference, Tokyo, Japan, September 2019. Author SK was the recipient of a University of Auckland PhD scholarship funded by CooperVision Inc. Author SNR was supported by a summer research scholarship awarded by the Faculty of Medical and Health Science, University of Auckland.

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Khanal, S., Rathod, S.N. & Phillips, J.R. The acute effect of atropine eye drops on the human full-field electroretinogram. Doc Ophthalmol 142, 315–328 (2021). https://doi.org/10.1007/s10633-020-09806-8

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  • DOI: https://doi.org/10.1007/s10633-020-09806-8

Keywords

  • Atropine
  • Electrophysiology
  • Myopia
  • Photoreceptors
  • Retina