Myopia – A 21st Century Public Health Issue

Starting with a World Health Organization (WHO)–associated global scientific meeting on myopia, which was held at the Brien Holden Vision Institute in Sydney, Australia in 2015, subgroups of researchers within The International Myopia Institute formed to address the major aspects of myopia.

These include the public health issues of myopia, sequelae of myopia, such as the increased risks of sight-threatening complications due to glaucoma, retinal detachment, and myopic macular degeneration, the classification of myopia, prevention of myopia and its complications, and evidence for treatments.

With myopia projected to affect 50% of the world population by 2050 and the fear that myopia could become the most common cause of irreversible blindness worldwide,1 The International Myopia Institute, thus, is a collaborative effort to bring together individuals from across all areas of myopia research.
As a first major step, The International Myopia Institute has edited in this special IOVS issue a series of white papers on defining and classifying myopia, potential interventions, clinical trials and instrumentation, industry guidelines and ethical considerations, clinical management guidelines, experimental models of emmetropization and myopia, and the genetics of myopia.

These articles, summarizing the current knowledge in the field and showing trends for future developments, may form a basis for further research, bridging gaps, and connecting people who so far had not intensively exchanged information and ideas. The IMI Myopia white paper reports initiative was chaired by Earl Smith and James Wolffsohn and facilitated by Monica Jong.
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Myopia Control Overview and Introduction

Prof. James Wolffsohn (Leader)
Committee members:

  • Prof. Ian Flitcroft
  • Dr. Kate Gifford
  • Dr. Monica Jong
  • Prof. Lyndon Jones
  • Prof. Caroline Klaver
  • Dr. Nicola Logan


  • Prof. Kovin Naidoo
  • Prof. Serge Resnikoff
  • Prof. Padmaja Sankaridurg
  • Prof. Earl Smith
  • Prof. David Troilo
  • Prof. Christine Wildsoet
With the growing prevalence of myopia, already at epidemic levels in some countries, there is an urgent need for new management approaches.

However, with the increasing number of research publications on the topic of myopia control, there is also a clear necessity for agreement and guidance on key issues, including on how myopia should be defined and how interventions, validated by well-conducted clinical trials, should be appropriately and ethically applied.

The International Myopia Institute (IMI) reports the critical review and synthesis of the research evidence to date, from animal models, genetics, clinical studies, and randomized controlled trials, by more than 85 multidisciplinary experts in the field, as the basis for the recommendations contained therein.

As background to the need for myopia control, the risk factors for myopia onset and progression are reviewed.
The seven generated reports are summarized:

  1. Defining and Classifying Myopia
  2. Experimental Models of Emmetropization and Myopia
  3. Myopia Genetics
  4. Interventions for Myopia Onset and Progression
  5. Clinical Myopia Control Trials and Instrumentation
  6. Industry Guidelines and Ethical Considerations for Myopia Control
  7. Clinical Myopia Management Guidelines

Keywords:
myopia control, myopic progression, clinical guidelines, definition, interventions
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Defining and Classifying Myopia

Prof. Ian Flitcroft (Leader)
Committee members:

  • Prof. Kyoko Ohno-Matsui
  • Prof. Lawrence Yannuzzi
  • Prof. Jost Jonas
  • Prof. Jugnoo Rahi
  • Prof. Serge Resnikoff


  • Dr. Monica Jong
  • Prof. Mingguang He
  • Prof. Kovin Naidoo
  • Dr. Susan Vitale
PURPOSE

We provide a standardized set of terminology, definitions, and thresholds of myopia and its main ocular complications.

METHODS

Critical review of current terminology and choice of myopia thresholds was done to ensure that the proposed standards are appropriate for clinical research purposes, relevant to the underlying biology of myopia, acceptable to researchers in the field,  and useful for developing health policy.

RESULTS

We recommend that the many descriptive terms of myopia be consolidated into the following  descriptive  categories:  myopia,  secondary  myopia,  axial  myopia,  and  refractive myopia. To provide a framework for research into myopia prevention, the condition of ‘‘pre-myopia’’ is defined. As a quantitative trait, we recommend that myopia be divided into myopia (i.e., all myopia), low myopia, and high myopia.
The current consensus threshold value for myopia is a spherical equivalent refractive error ≤ -0.50 diopters (D), but this carries significant risks of classification bias. The current consensus threshold value for high myopiais a spherical equivalent refractive error ≤ -6.00 D. ‘‘Pathologic myopia’’ is proposed as thecategorical term for the adverse, structural complications of myopia. A clinical classification is proposed to encompass the scope of such structural complications.

CONCLUSIONS

Standardized definitions and consistent choice of thresholds are essential elements of evidence-based medicine. It is hoped that these proposals, or derivations from them, will facilitate rigorous, evidence-based approaches to the study and management of myopia.

Keywords: myopia, myopia classification, myopia definitions, high myopia,   myopia thresholds, high myopia, pathologic myopia
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Experimental Models of Emmetropization and Myopia

Prof. Earl Smith and Prof. David Troilo (Leaders)
Committee members:

  • Prof. Siegfried Wahl
  • Dr. Lisa Ostrin
  • Dr. Kee Chea-su
  • Dr. Tim Gawne
  • Dr. Andrei Tkatchenko


  • Prof. Machelle Pardue
  • Dr. Regan Ashby
  • Dr. Debora Nickla
  • Dr. Jody Summers
  • Dr. Falk Schroedl
The results  of  many  studies  in  a  variety  of  species  have  significantly  advanced  ourunderstanding of the role of visual experience and the mechanisms of postnatal eye growth,and the development of myopia.

This paper surveys and reviews the major contributionsthat experimental studies using animal models have   made to our thinking about emmetropization and development of myopia.

These studies established importantconcepts informing our knowledge of the visual regulation of eye growth and refractivedevelopment and have transformed treatment strategies for myopia. Several major findings have come from studies of experimental animal models.

These include the eye’s ability todetect  the  sign  of  retinal  defocus  and  undergo  compensatory  growth, the local retinalcontrol of eye growth, regulatory changes in choroidal thickness, and the identification of components in the biochemistry  of  eye  growth  leading to the characterization of signal cascades regulating eye growth and refractive state.
Several of these findings provided theproofs of concepts that form the scientific basis of new and effective clinical treatments forcontrolling myopia progression in humans.

Experimental animal models continue to provide new insights into the cellular and  molecular mechanisms of eye growth control, including the identification of potential  new targets for drug development and future treatments needed to stem the increasing prevalence of myopia and the vision threatening conditions associated with this disease.

Keywords: myopia, emmetropization, animal models, visual regulation, eye growth
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Myopia Genetics

Prof. Caroline Klaver (Leader)
Committee members:

  • Dr. Virginie Verhoeven
  • Prof. Chris Hammond
  • Dr. Magda A. Meester-Smoor
  • Dr. Milly S. Tedja
  • Dr. Jaakko Kaprio


  • Dr. Annechien E.G. Haarman
  • Prof. David A. Mackey
  • Prof. Jeremy A. Guggenheim
  • CREAM Consortium
The knowledge on the genetic background of refractive error and myopia has expanded dramatically in the past few years. This white paper aims to provide a concise summary ofcurrent genetic findings and defines the direction where development is needed.

We performed an extensive literature search and conducted informal discussions with key stakeholders. Specific topics reviewed included common refractive error, any and high myopia, and myopia related to syndromes.

To date, almost 200 genetic loci have been identified for refractive error and myopia, and risk variants  mostly carry low risk but are highly prevalent in the general population.

Several genes for secondary syndromic myopia overlap with those for common myopia. Polygenic risk scores show overrepresentation of high myopia in the higher deciles of risk.
Annotated genes have a wide variety of functions, and all retinal layers appear to be sites of expression. The current genetic findings offer a world of new molecules involved in myopiagenesis. As the missing heritability is still large, further genetic advances are needed.  

This Committee recommends expanding large-scale, in-depth genetic studies using complementary big data analytics, consideration of gene-environment effects by thorough measurement of environmental exposures, and  focus on subgroups with extreme phenotypes and high familial occurrence.

Functional characterization  of associated variants is simultaneously needed to bridge the knowledge gap between sequence variance and consequence for eye growth.

Keywords: myopia, refractive error, genetics, GWAS, GxE interactions
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Interventions for Controlling Myopia Onset and Progression

Prof. Christine Wildsoet (Leader)
Committee members:

  • Dr. Klaus Trier
  • Prof. Seang Mei Saw
  • Prof. Padmaja Sankaridurg
  • Dr. Jeff Walline
  • Prof. Jez Guggenheim


  • Prof. Audrey Chia Wei Lin
  • Prof. Pei-Chang Wu
  • Dr. Scott Read
  • Dr. Pauline Cho
  • Dr. Jan Polling
Myopia has been predicted to affect approximately 50% of the world’s population basedon trending myopia prevalence figures. Critical to minimizing the associated  adversevisual consequences of complicating ocular pathologies are interventions to  prevent or delay the onset of myopia, slow its progression, and to address the problem of mechanical instability of highly myopic eyes.

Although treatment approaches are growing in number, evidence of treatment efficacy  is variable.  This article reviews research behind such interventions under four categories: optical, pharmacological, environmental (behavioral), and surgical. In summarizing the evidence of efficacy, results from randomized controlled trials have  been given most weight, although such data are very limited for some treatments.
The overall conclusion of this review is that there are multiple avenues for intervention worthy of exploration in all categories, although in the case of optical, pharmacological, and behavioral interventions for preventing or slowing progression  of myopia, treatment efficacy at an individual level appears quite variable, with no one treatment being 100% effective in all patients.  

Further research is critical to understanding the factors underlying such variability and  underlying mechanisms, to guide recommendations for combined treatments. There is  also room for research into novel treatment options.

Keywords: myopia control, optical, pharmacological, behavioral, surgical
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Clinical Myopia Control Trials and Instrumentation Report

Prof. James Wolffsohn (Leader)
Committee members:

  • Dr. David Berntsen
  • Dr. Alexandra Benavente
  • Dr. Takohiro Hiraoka
  • Dr. Scott Read
  • Dr. David Atchison
  • Dr. Takashi Fujikado
  • Dr. Hetal Buckhurst
  • Dr. Pete Kolbaum
  • Dr. Arthur Bradley


  • Dr. Arthur Bradley
  • Dr. Debbie Jones
  • Dr. Hidemasa Torii
  • Dr. Michael Collins
  • Dr. Nicola Logan
  • Dr. Linda Lundstrom
  • Masakazu Hirota
The evidence-basis based on existing myopia control trials along with the supporting academic literature were reviewed; this informed recommendations on the outcomes  suggested from clinical trials aimed at slowing myopia progression to show the effectiveness of treatments andthe impact on patients.

These outcomes were classified as primary (refractive error and/or axial length),  secondary (patient reported outcomes and treatment compliance), and exploratory (peripheral refraction, accommodative changes, ocular alignment, pupil size, outdoor activity/lighting levels, anterior and posterior segment imaging, and tissue biomechanics).
The currently available instrumentation, which the literature has shown to best achieve the primary and secondary outcomes, was reviewed and critiqued. Issues relating to study design and patient selection were also identified. 

These findings and consensus from the International Myopia Institute members led to final recommendations to inform future instrumentation developmentand to guide clinical trial protocols.

Keywords:  myopia control, myopia progression, clinical trial guidelines, instrumentation, recommendations
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Industry Guidelines and Ethical Considerations for Myopia Control

Prof. Lyndon Jones (Leader)
Committee members:

  • Dr. Fuen Vera-Diaz
  • Dr. Jacinto Santodomingo-Rubido
  • Dr. Timo Kratzer
  • Dr. Katrina Schmid
  • Prof. Jose Gonzales-Meijome
  • Dr. Stephanie Ramdass
  • Dr. Steve Newman


  • Prof. Jason Nichols
  • Dr. Bjorn Drobe
  • Dr. Lyle Gray
  • Prof. Donald Tan
  • Dr. Kah Ooi Tan
  • Dr. Arne Ohlendorf
  • Dr. Yee Ling Wong
PURPOSE

To  discuss guidelines  and  ethical considerations  associated  with the  developmentand prescription of treatments intended for myopia control (MC).

METHODS

Critical review of published papers and guidance documents was undertaken, with a view to carefully considering the ethical standards associated with the investigation, development, registration, marketing, prescription, and use of MC treatments.

RESULTS

The roles and responsibilities of regulatory bodies, manufacturers, academics, eyecare practitioners, and patients in the use of MC treatments are explored.

Particular attention is given to the ethical considerations for deciding whether to implement a MC strategy andhow to implement this within a clinical trial or practice setting. Finally, the responsibilities in marketing, support, and education required to transfer required knowledge and skills to eyecare practitioners and academics are discussed.
CONCLUSIONS

Undertaking MC treatment in minors creates an ethical challenge for a wide variety of stakeholders. Regulatory bodies, manufacturers, academics, and clinicians all share an ethical responsibility to ensure that the products used for MC are safe and efficacious and that patients understand the benefits and potential risks of such products.

This International Myopia Institute report highlights these ethical challenges and provides stakeholders with recommendations and guidelines in the development,  financial support, prescribing, and advertising of such treatments.

Keywords: conflict of interest, ethical prescribing, informed consent, medical device, myopia control
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Clinical Myopia Management Guidelines

Dr. Kate Gifford (Leader)
Committee members:

  • Dr. Langis Michaud
  • Dr. Tom Aller
  • Dr. Pauline Kang
  • Dr. Kathryn Richdale
  • Prof. Carly Lam
  • Mr. Jeroen Mulder


  • Dr. Dirk Seidel
  • Dr. Kathryn Saunders
  • Dr. Maria Liu
  • Dr. Willem Tideman
  • Dr. Janis Orr
  • Prof. Kathy Rose
Best practice clinical guidelines for myopia control involve an understanding of the epidemiology of myopia, risk factors, visual environment interventions, and optical and pharmacologic treatments, as well as skills to translate the risks and benefits of a given myopia control treatment into lay language for both the patient and their parent or care giver.

This report details evidence-based best practice management of the pre-, stable, and the progressing myope, including risk factor identification, examination, selection of treatment strategies, and guidelines for ongoing management.
Practitioner considerations such as informed consent, prescribing off-label treatment, and guides for patient and parent communication are detailed.

The future research directions of myopia interventions and treatments are discussed, along with the provision of clinical references, resources, and recommendations for continuing professional education in this growing area of clinical practice.

Keywords: myopia control, myopia progression, clinical considerations, patient communication, practitioner education
©2019 Global Myopia Centre. A Brien Holden Vision Institute Limited Initiative. All Rights Reserved.

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