Open Access
Special Issue  |   February 2019
IMI – Clinical Myopia Control Trials and Instrumentation Report
Author Affiliations & Notes
  • James S. Wolffsohn
    Ophthalmic Research Group, Aston University, Birmingham, United Kingdom
  • Pete S. Kollbaum
    Indiana University, School of Optometry, Bloomington, Indiana, United States
  • David A. Berntsen
    The Ocular Surface Institute, College of Optometry, University of Houston, Houston, Texas, United States
  • David A. Atchison
    School of Optometry and Vision Science, Institute of Health and Biomedical Innovation, Queensland University of Technology, Australia
  • Alexandra Benavente
    SUNY College of Optometry, New York, New York, United States
  • Arthur Bradley
    Indiana University, School of Optometry, Bloomington, Indiana, United States
  • Hetal Buckhurst
    School of Health Professions, Peninsula Allied Health Centre, Plymouth University, Plymouth, United Kingdom
  • Michael Collins
    School of Optometry and Vision Science, Institute of Health and Biomedical Innovation, Queensland University of Technology, Australia
  • Takashi Fujikado
    Department of Applied Visual Science, Osaka University Graduate School of Medicine, Osaka, Japan
  • Takahiro Hiraoka
    Department of Ophthalmology, Faculty of Medicine, University of Tsukuba, Ibaraki, Japan
  • Masakazu Hirota
    Department of Applied Visual Science, Osaka University Graduate School of Medicine, Osaka, Japan
  • Debbie Jones
    School of Optometry and Vision Science, University of Waterloo, Waterloo, Ontario, Canada
  • Nicola S. Logan
    Ophthalmic Research Group, Aston University, Birmingham, United Kingdom
  • Linda Lundström
    Applied Physics, KTH Royal Institute of Technology, Sweden
  • Hidemasa Torii
    Department of Ophthalmology, Keio University School of Medicine, Tokyo, Japan
  • Scott A. Read
    School of Optometry and Vision Science, Institute of Health and Biomedical Innovation, Queensland University of Technology, Australia
  • Kovin Naidoo
    African Vision Research Institute, University of KwaZulu-Natal, Durban, South Africa
  • Correspondence: James S. Wolffsohn, Life and Health Sciences, Aston University, Aston Triangle, Birmingham B4 7ET, UK; j.s.w.wolffsohn@aston.ac.uk
Investigative Ophthalmology & Visual Science February 2019, Vol.60, M132-M160. doi:https://doi.org/10.1167/iovs.18-25955
  • Views
  • PDF
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      James S. Wolffsohn, Pete S. Kollbaum, David A. Berntsen, David A. Atchison, Alexandra Benavente, Arthur Bradley, Hetal Buckhurst, Michael Collins, Takashi Fujikado, Takahiro Hiraoka, Masakazu Hirota, Debbie Jones, Nicola S. Logan, Linda Lundström, Hidemasa Torii, Scott A. Read, Kovin Naidoo; IMI – Clinical Myopia Control Trials and Instrumentation Report. Invest. Ophthalmol. Vis. Sci. 2019;60(3):M132-M160. doi: https://doi.org/10.1167/iovs.18-25955.

      Download citation file:


      © ARVO (1962-2015); The Authors (2016-present)

      ×
  • Supplements
Abstract

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 and the 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 development and to guide clinical trial protocols.

1. Introduction, Scope, and Guiding Principles
This report has identified the primary, secondary, and exploratory outcomes suggested from clinical trials for slowing myopia progression, showing the effectiveness of treatments and the impact on patients. Currently available instrumentation that the literature has shown to be the best to achieve the primary and secondary outcomes was reviewed and critiqued. Issues were also identified relating to study design and patient selection in adherence to the tenets of the Declaration of Helsinki and ethics. These findings and consensus from the International Myopia Institute members led to final recommendations to inform future instrumentation development and guide clinical trial protocols. 
2. Study Design
When conducting a study to determine the efficacy of a treatment for myopia control, it is critical to utilize sound clinical trial methodology. Decisions when designing a standardized clinical trial not only minimize variability and bias, they also maximize generalizability and allow for easier comparison among studies. There are many decisions to be made when designing a clinical trial. 
2.1 Study Length
The average age of myopia onset in the United States and Singapore is eight years of age, and the average age at which myopia progression is reported to cease is roughly 16 years, although progression at slower rates can also be observed in children older than 16 years.13 However, age of myopia onset, rate of progression, and duration of progression vary internationally, with Asians having earlier onset, faster rates of progression, and longer duration of progression than other races.4,5 Because myopia control interventions will be applied for multiple years throughout the time myopia is progressing, it is important that clinical trials evaluate efficacy over a long period to ensure continued efficacy beyond any initial treatment effect.6 The Correction of Myopia Evaluation Trial (COMET) demonstrates this point well. This large, well-conducted clinical trial evaluating the efficacy of Progressive Addition Lens spectacles versus standard spectacles, found a treatment effect after 1 year; however, the treatment effect did not continue to accumulate over the 2 subsequent years of the trial.7 Evidence of diminishing efficacy beyond the first year was also noted in other bifocal and Progressive Addition Lens spectacle studies8,9 and orthokeratology (OK) studies.10 
As demonstrated, the extrapolation of a 1-year treatment effect to multiple years can lead to incorrect conclusions. To employ the best evidence-based practice, it is important that eye care providers have clinical trial research to support the multi-year use of a particular treatment. If a treatment is shown to provide an effect only over a short time period, this is also valuable information that can allow a practitioner to make an informed decision regarding when to change treatment modalities. The length of the trial must also be balanced with feasibility; as trial length increases, the ability to retain participants becomes more difficult, progression begins to slow naturally, and costs increase. For this reason, 3 years is the recommended minimum length of a clinical trial assessing the efficacy of a treatment for myopia control. 
2.2 Participant Selection Criteria
This section is informed by 24 recent evidence-based papers from four categories of clinical trials. Category 1 included multifocal spectacles9,1114 and under-correction with single vision spectacles.15,16 Category 2 included OK lens trials.1720 Category 3 included bifocal contact lenses6,2123 and multifocal contact lenses.2428 Category 4 included atropine treatment.2932 Studies on outdoor activities were not included because the cohorts were substantially different from those in the other four categories. 
2.2.1 Refractive Error
2.2.1.1 Spherical or Spherical Equivalent Refractive Error
Spherical refractive error was part of the inclusion criteria in categories 2 and 3, whereas spherical equivalent refractive error was mostly adopted in categories 1 and 4. Because the amount of astigmatism was limited in each trial (see Section 2.2.1.4) and the value typically is no greater than 1.50 D, the choice of whether to use spherical or spherical equivalent for the inclusion criteria was generally inconsequential. For the evaluation of myopia progression, spherical equivalent refractive error was adopted in all studies except OK studies. The use of cycloplegia is discussed in Section 2.6 and refractive error determination in Section 3.1.2. 
2.2.1.2 Progression Over Period Prior to Enrollment
Four trials adopted a minimum progression rate prior to enrollment as an inclusion criteria. 
One trial adopted one 0.3 D/year,26 one 0.5 D/year,33 one 1.0 D/year,31 and one 0.5 D progression since the last visit.21 Only the latter study reported that progression was assessed “based on clinical records, results of spectacle neutralization, or written prescriptions.”21 The criteria were adopted in recent trials to confirm the prevention effect among participants who have at least a minimum level of recent myopia progression. However, deciding progression on the basis of typically two “noisy” data points could lead to errors in participant selection, whereas recruiting non-progressing myopes could cause overestimation (if in the treatment group) or underestimation (if in the control group) of the treatment effect and may be considered unethical. 
2.2.1.3 Astigmatism Limit
An equal number of studies adopted a maximum of 1.00 D or 1.50 D (n = 10 each) with two adopting 1.25 D (Table 1). 
Table 1
 
Selection Criteria in Recent Myopia Control Clinical Trials
Table 1
 
Selection Criteria in Recent Myopia Control Clinical Trials
2.2.1.4 Anisometropia
Most studies (n = 8) have adopted a maximum permissible limit of 1.50 D, but others have selected ≤1.00 D (n = 5), ≤1.25 D (n = 1), or ≤2.00 D (n = 2) (Table 1). 
2.2.2 Age
While one study adopted a minimum age of 5 years, most adopted a minimum of 6 years of age. Most trials adopted 12 years as the maximum age (n = 6), but others ranged from 7 years (n = 2) to 18 years (n = 2). There appears to be no particular trend within inclusion criteria for the modality of intervention (Table 1). 
2.2.3 Previous Optical Correction
Previous optical correction may affect the efficacy of a myopia control intervention. Generally, spectacles and monofocal soft contact lens (SCL) are accepted as options for previous correction; however, in an under-correction spectacle study,16 participants were excluded who had worn an under-corrected spectacle prescription previously (i.e., had not been prescribed their full myopic refractive correction). Rigid contact lens wearers were specifically excluded, mostly in studies involving multifocal or bifocal (SCL) and OK studies. 
2.2.4 Previous Myopia Treatment
Patients with a history of previous myopia control treatment were excluded in all studies. 
2.2.5 Exclusion Criteria
Participants with ocular pathology, such as retinal detachment, were excluded in all studies, as were patients with strabismus. Studies generally exclude participants who are on medications that may affect pupil size, accommodation, or have an impact on the ocular surface (such as allergy medications). The literature does not always outline specific exclusion criteria other than prescription range. Systemic disease that may affect vision, vision development, or contact lens wear (such as diabetes and Down syndrome), were explicitly excluded in a recent study (Table 2).28 
Table 2
 
Typical Inclusion/Exclusion Criteria, Although Should Be Altered to Address Specific Study Hypothesis
Table 2
 
Typical Inclusion/Exclusion Criteria, Although Should Be Altered to Address Specific Study Hypothesis
2.3 Appropriate Control Group
A placebo-controlled clinical trial in which participants do not know their group assignment is generally considered the gold standard. Ideally, the control or sham (placebo) treatment cannot be distinguished from the active treatment with the only difference between the treatment and control being a hypothesized intervention, such as an optical design or active pharmaceutical agent.35,36 That said, the most appropriate control group will depend on the intervention being studied. Studies with no control group are unable to demonstrate treatment efficacy; for example, the rate of myopia progression decreases naturally with age, so it is not possible to distinguish between naturally declining progression and reduced progression attributable to the treatment, without a simultaneously conducted control group.1,4 Likewise, studies utilizing historical control groups also allow the introduction of unknown sources of bias. In several studies, historical control groups have been used (Table 3). An appropriate control group manages potential sources of bias, alleviating many of these concerns. Treatment and control groups ideally should be matched for factors such as age, starting refractive error, time outdoors, ethnicity, and parental myopia status since these factors are all known to influence progression rate. It is often a challenge to keep participants in a control group, particularly if the efficacy of the treatment group becomes or is perceived to be established. 
Table 3
 
Control Group, Randomization, and Masking
Table 3
 
Control Group, Randomization, and Masking
2.3.1 Pharmaceutical Studies
The recommended placebo is the vehicle used in the active treatment intervention but without the active pharmaceutical agent being evaluated in the treatment group. By using a control that differs from the treatment drug's active ingredient, any effect can be isolated to the specific molecule being evaluated. When this is not possible, the control treatment should mirror the active treatment medication as closely as possible. In either case, the administration regimen should be the same whether a participant is in a treatment or control group. In atropine studies, past studies have applied a vehicle placebo to the control group (Table 3). 
2.3.2 Contact Lens Studies
The best choice for a control group depends on the treatment modality being evaluated. One prominent theory of myopia control hypothesizes that peripheral myopic defocus slows progression.4 Both single vision spectacles and spherical SCL change peripheral defocus from the uncorrected state by amounts that vary between lens designs and by lens power.3739 A control contact lens made of the same material is ideal and, if possible, the optics of the control lens should not change peripheral defocus. However, current options change the peripheral refraction and spherical aberration40,41 so, ideally, the “optimal” lens may be one with known levels of spherical aberration that do not vary with lens power. In multifocal or bifocal SCL studies, control groups have generally used single-vision SCL (Table 3). Two randomized controlled trials have shown no clinically meaningful difference in myopia progression between single vision contact lenses and single vision spectacles.42,43 However, such studies do not allow participant masking. 
2.2.3 OK Studies
There is no ideal control group that allows double masking. Spherical gas permeable contact lenses, SCL, or spectacles must be worn during the day to correct vision, unlike OK lenses where the child typically wears the contact lens at night and needs no correction during the day to see clearly after removal. Alignment fitted gas permeable contact lenses can flatten the cornea and thus contaminate the apparent influence of the lens on refractive error.44 For these reasons, spectacle lenses are adequate control lenses. There is also evidence that spherical surfaced SCL do not alter myopia progression, making them a viable option as well42; however, even these lenses (brand identified by personal communication with the principal investigator) had levels of spherical aberration that varied with lens power (minus lenses inducing negative spherical aberration). Therefore, presumably, the optics of the lenses change peripheral defocus, so not every person evaluated had “the same” control. In previous multifocal spectacle studies, control groups generally used single vision spectacle lenses (Table 3). 
2.3.4 Multifocal Spectacle Studies
Control groups generally used single-vision spectacle lenses. It is not possible to mask bifocal spectacle lenses. 
2.4 Randomization and Stratification
Randomization is a critical part of a clinical trial that distributes potential confounding baseline characteristics (both known and unknown) between the treatment groups and the control group.35,36 Randomization assignments should not be available to investigators in advance and should be accessible only after the investigator has confirmed the participant's eligibility to be enrolled in the clinical trial; this is best administered using an online portal that requires key eligibility checks prior to revealing the randomization assignment. 
Stratifying randomization by key factors known to influence myopia progression—such as age and race/ethnicity—should be considered. Stratification should be limited to a few key factors. To avoid detrimental effects from over-stratifying, a statistician should always be consulted during the planning stage of any study to determine how many stratification factors can be considered based on the planned size of the study. To help ensure more equal allocation of important stratification factors between the treatment and control group, block randomization using random, even, small block sizes should be employed. Randomization schemes should be generated using appropriate statistical software. 
An intent-to-treat philosophy should be used when analyzing data. Once a participant is randomized to a particular group, that participant should always be analyzed as part of the assigned treatment group, even if the participant later discontinues treatment or changes treatment groups during the study. The intent-to-treat principle preserves randomization and prevents the introduction of bias during analyses. A per-protocol population is a subset of the intent-to-treat population who completed the study in accordance with the protocol. Users of this intent-to-treat philosophy should be aware that treatment effects might be conservative (e.g., due to noncompliance), and interpretation of endpoints might be difficult if large numbers of participants change over to the opposite treatment arm. 
In most previous studies, randomized controlled trials were adopted. Three studies using OK did not use randomization.17,18,20 These studies had inclusion criteria, but participants and their parents had the choice between OK or single vision spectacles. Several studies were stratified by age or refraction (Table 2). 
2.5 Masking
Clinical trials should utilize double masking whenever possible to minimize the potential for bias (i.e., both the participant and the examiner collecting primary outcome data should be masked to the participant's treatment assignment). Masking of the participant helps ensure they remain compliant with their assigned treatment and do not change their behavior in a way that might influence the outcome. In the case of OK, participant masking is not possible (see Section 2.3). At a minimum, investigators who assess study outcomes should always be masked to minimize the introduction of unintended bias by the investigator during the study due to consciously or subconsciously treating participants differently.35,36 
In the previous studies for spectacle, SCL, and atropine, masking was usually employed. In OK studies, masking could not be adopted as the control group used spectacles. However, examiners who were masked with regard to the lens assignments performed portions of the clinical examinations, including refraction, axial length measurement, and prescribing spectacles. An unmasked investigator performed allocation using a random number table or a computer software program that generated a random sequence. 
2.6 Cycloplegia
Cycloplegia should be used when measuring primary outcomes in studies of myopia progression to minimize variability. The recommended regimen that has been used in multiple clinical trials is two drops of 1% tropicamide separated by 5 minutes with primary outcome measures commencing 30 minutes after the first drop of tropicamide is instilled. This protocol has been previously evaluated by Manny and colleagues45 in an ethnically diverse cohort of children enrolled in the Correction of Myopia Evaluation Trial (COMET) and determined to be an appropriate method for cycloplegia. Residual accommodation was found to be small (0.38 ± 0.41 D). Work comparing the effects of cyclopentolate and tropicamide also found no meaningful difference in measured refractive error between agents 30 minutes after instillation.46 Given the unnecessarily longer-lasting cycloplegic and mydriatic effects of cyclopentolate versus 1% tropicamide as well as minimal additional gain in cycloplegia with cyclopentolate in myopic children, 1% tropicamide is recommended in optical treatment studies. If used consistently throughout the study, 1% tropicamide provides adequate cycloplegia for outcome measures while balancing the importance of retaining children in longitudinal clinical trials, thereby minimizing the duration of mydriasis and cycloplegia upon completion of each study visit. As atropine also causes cycloplegia, the use of a cycloplegic agent for refraction with less potency could confound the assessment of the treatment effect. In studies involving pharmaceutical interventions, the baseline refractive error and biometry measurements used to calculate the change in myopia progression and axial growth should be performed shortly after the child has begun treatment using their assigned intervention so that the baseline also has the combined effect of the cycloplegics. 
2.7 Assessment of Rebound
The question of rebound after ceasing treatment is important to consider for any myopia control treatment. For a treatment to be beneficial, the effect must be maintained after treatment is stopped. Studies of atropine demonstrate a rebound (accelerated eye growth) after discontinuing use and is greatest with higher concentrations of atropine.47 While studies utilizing multifocal spectacles and SCL have not produced evidence of a rebound,34 it is possible that more efficacious optical treatments might be prone to more accelerated eye growth after discontinuation of treatment. 
In studies aimed to evaluate the potential presence of accelerated progression after ceasing treatment, the minimum recommended time period over which a rebound effect should be evaluated is 1 year due to naturally occurring seasonal variations in myopia progression (slower growth in the summer versus the winter).48 Assessing for a rebound effect is best accomplished in a clinical trial in which children assigned to the treatment group are switched to the control treatment, with all children in the trial then followed using the control treatment. However, ethical implications of this approach should be considered. 
2.8 Safety
2.8.1 Standardized Adverse Event Reporting
With any new or developing medical technology, it is important to continuously evaluate the cost versus benefit of the technology. For example, for children wearing SCLs, it should be considered whether the benefits provided by the contact lens (such as in correcting vision or controlling myopia progression) outweigh any ocular health risks. 
Thirty collaborating centers of the World Health Organization49 have established common definitions of terms related to adverse event reporting. Specifically, an adverse event is “any untoward medical occurrence in a patient or clinical investigation participant” administered a drug or device, which “does not have to have a causal relationship.” Therefore, an adverse event can “be any unfavorable and unintended sign,” symptom or disease associated with the use of a medical device or drug.50 It is necessary to make a risk-benefit judgment for approval or use of a product; to do this effectively, the classification and reporting of adverse events should occur in a standardized manner and timeframe. If occurring within a study, this event information must also be communicated to the manufacturer, care provider, patient constituencies, and institutional review board. 
Contact lens adverse events can be classified in several ways, such as graphically represented by a decision tree.51 Specifically, an adverse event should first be classified as either “serious” or “non-serious.” Serious events are those that are life threatening, require inpatient or prolonged hospitalization, or may cause permanent impairment or damage. An important serious adverse event related to the eye and contact lens use is the occurrence of microbial keratitis. Non-serious events may include red eye and discomfort (see Section 2.8.2). Adverse events are often further subdivided in terms of severity (such as mild, moderate, or severe), device-related (often referred to as a “device effect”), and whether it was unanticipated versus anticipated (often referred to as “not unanticipated” because anticipated suggests that an unfavorable occurrence is likely to occur). Specifically, adverse events at all times should be differentiated from normal or anticipated consequences of contact lens use, such as minor eye dryness52 and changes in corneal morphology.5355 
Many governmental organizations around the globe protect consumers by creating device reporting methods. For example, in the United States, the U.S. Food and Drug Administration (FDA) Medical Device Reporting (MDR) regulation (21 CFR 803) contains mandatory requirements for manufacturers, importers, and device user facilities to report certain device-related adverse events and product problems. The FDA also encourages healthcare professionals, patients, caregivers, and consumers to submit voluntary reports of significant adverse events or product problems with medical products to MedWatch, the FDA's Safety Information and Adverse Event Reporting Program.56 Other organizations around the globe have similar regulations and provide similar reporting systems, such as Health Canada and the Australian government's Therapeutic Goods Administration. 
Infiltrative adverse events among patients of all ages and lens types have been reported to occur at a low incidence (such as corneal infiltrative event incidence of 21 per 10,000 SCL wearing years).57,58 Specifically, the incidence of events in children has not been found to be higher than that in adults. In fact, in the 8- to 11-year age range (a range where myopia control lenses might become very commonly utilized), estimated incidence of events is actually lower than in adults.58 Monitoring, classification, and reporting methods should be specifically outlined in any research study. Additionally, practitioners should inform participants and parents of pediatric wearers about normally anticipated consequences of contact lens wear, potential adverse events, and what to do if adverse events occur. Participants (and, in case of child participants, their parents) should be informed about the necessity of reporting adverse events. 
Pharmaceutical treatment of myopia is associated with short-term effects such as photophobia and possible long-term effects such as light-induced retinal damage or cataract formation.59 The use of atropine for myopia control (0.5%) resulted in over 80% of children having adverse events (whether reported by the parents or the children themselves), such as photophobia (60%–82%), systemic flushes (3%–6%), infections such as conjunctivitis/blepharitis (0%–3%), headaches (7% reported by children who maintained therapy compared to 31% in those that ceased therapy), and reading problems (∼25% in those who maintained therapy compared to ∼80% in those that ceased therapy).31 Other studies have reported no serious adverse events.29,32 For pirenzepine ophthalmic gel (2%), similar mild to moderate adverse events were experienced in one of two studies, with serious adverse events deemed unrelated to the treatment.60,61 
2.8.2 Ocular Health
At the outset of any clinical trial, a series of assessments determine baseline data for trial participants. Baseline information that is collected in a standardized way can be used for various reasons, including characterization of participants, analysis of outcomes based on baseline measurements, and treatment effects based on presenting characteristics.62 Examples can include presence or absence of heterophoria, baseline amount of myopia, and accommodative function. These may inform exclusion criteria or be used to assess the impact of a myopia control treatment on ocular physiology. Evaluation of the posterior pole is critical for all myopia control studies to identify any retinal changes or pre-existing retinal conditions that may exclude participation in a clinical trial, require a participant to withdraw from a clinical trial, or require the participant to be referred for further assessment. Fundus abnormalities in asymptomatic patients are uncommon. It has been estimated that fundus anomalies occur in approximately 2.5% of patients under the age of 20, with less than 1% of those findings being clinically significant.63 It is well known that myopia is associated with an increased risk of many ocular diseases, including myopic maculopathy, retinal detachment, glaucoma, and cataract.6467 These risk factors increase with increasing age and increasing magnitude of myopic refractive error. In a study on myopic maculopathy, the incidence in patients with a prescription less myopic than 5.0 D was 0.42%, compared with 25.3% in patients with more myopic prescriptions.68 Findings have been similar for the risk of retinal detachments, with an increased risk in patients with more myopic prescriptions, but even lower levels of myopia (less myopic than −3.0 D) have been shown to have a three times increased risk of retinal detachment compared to emmetropic patients.69 However, all levels of myopia increase the risk of retinal pathology, so there is no physiologically safe (or non-pathological) level of myopia (see accompanying IMI – Defining and Classifying Myopia Report).70,87 
A dilated fundus examination should be performed on participants at baseline and subsequent annual or periodic visits. In a study involving pediatric patients, 51% of participants had one or more peripheral anomalies (albeit mainly clinically insignificant) that were detected in a dilated fundus examination that were otherwise undetected in a nondilated examination.71 The use of a binocular indirect ophthalmoscope (BIO) is considered the gold-standard for assessing the peripheral fundus. Typically, a 20 D lens is used in conjunction with the BIO, but for younger patients, a 28 D lens can be more useful as it gives a slightly larger field of view.72 
A clinical trial involving contact lenses or pharmaceuticals will require a full anterior assessment at each visit. The slit lamp biomicroscope offers a variety of illumination techniques and magnification options to examine the anterior chamber.73,74 A full slit lamp examination utilizes various techniques in a coordinated, systematic way to ensure a full examination of all relevant anterior structures; the results should be recorded with an appropriate grading technique.75 
Associations have been reported between myopia progression, higher levels of esophoria, and accommodative lag in some studies (see Sections 3.3.2 and 3.3.3), and binocular vision problems are relatively common in children76,77; thus, it is important to perform a binocular vision assessment at baseline (potentially as part of exclusion criteria to ensure they are not a confounding factor) and at periodic times throughout a myopia control study, such as during annual assessments. Typically, participants with a manifest strabismus would be precluded from participating in a myopia control clinical study, although this is not always specifically stated in the reported exclusion criteria (see Section 2.5). 
2.8.3 Vision
2.8.3.1 Visual Acuity
LogMAR visual acuity is measured in virtually every clinical trial assessing myopia control treatments. It can be both an inclusion/exclusion criterion (participants need to have a visual acuity better than an arbitrary value) and to assess any negative (safety) impact of optical, pharmaceutical, or environmental modifications both during (reduced vision could affect educational performance and mobility) and after treatment (permanent visual loss would be a serious adverse event; see Section 2.8.1). When measuring visual acuity, considerations include what correction should be worn (unaided, mean spherical equivalent or full sphero-cylindrical correction, habitual visual correction or the device), whether the measures are monocular or binocular and the target distance (far, near, or a full defocus curve). Contrast sensitivity is measured in fewer studies, but may be more sensitive to detect reductions in functional vision.78 Some studies have shown small reductions in high-contrast visual acuity and contrast sensitivity when wearing off-label multifocal contact lenses,79 while other studies showed no significant effects of other multifocal contact lens designs on visual acuity or contrast sensitivity.80,81 Low dose (0.01%) atropine has shown no significant effect on visual acuity in young adults over a 5-day period.82 
Some studies use Snellen visual acuity charts and convert to logMAR, negating the benefits of the standardization and uniformity of logMAR charts.83 Using Snellen visual acuity is discouraged for reporting outcomes; studies collecting Snellen acuity should not convert these to logMAR for reporting, which gives the false perception that logMAR was collected. There is considerable variation in the way visual acuity measurements are expressed (logMAR and decimal notation can easily be confused), and frequently the charts and the procedures used for visual acuity testing are inadequately described.84 As methodology can markedly affect visual acuity scores, studies should provide enough detail about their methodologies to allow others to replicate and benchmark against them. 
2.8.3.2 Functional Vision
Reading speed has been found to correlate better with vision related quality of life (satisfaction with functional vision) than does traditional high contrast visual acuity. However, few myopia control studies have used reading speed, perhaps due to the time taken to conduct the measurement. Of the studies to assess reading speed to date, no difference from controls was found with an off-label multifocal contact lens design79 or with short-term use of atropine 0.01% in Caucasian young adults.82 Other aspects of near work are generally captured in questionnaires85 (see Section 3.2.1). 
2.8.4 Dysphotopsia
Dysphotopsia, such as glare, is of interest in myopia control strategies that affect light levels, alter the light spectrum entering the eye, dilate the pupil, or impose optical junctions (such as different or alternating power SCL optical zones) within the pupil. However, few studies have examined the potential adverse effect of dysphotopsia associated with myopia control strategies. Loughman and Flitcroft assessed glare, albeit in a young adult population over a 5-day use period, 0.01% atropine, showing a slight increase in symptoms, but no impact on quality of life.82 A recent paper examined the role of short-wavelength filtering lenses in delaying myopia progression and amelioration of asthenopia in juveniles, finding no effect over a year's duration on refraction or axial length compared to controls, but a reduction of the effect of glare on contrast sensitivity.86 Future myopia control studies should elicit whether dysphotopsia has been increased by the treatment strategy. 
2.9 Clinically Meaningful Effect
It is important that similar reporting criteria are utilized across studies to maximize the comparability of results. The definition of a clinically meaningful effect is also important for determining success of any myopia treatment. Another important question is how large a treatment effect is needed in each year of a multi-year clinical trial to be considered meaningful. 
The mean and standard deviation of the difference in progression between groups should be reported for comparability to previously published myopia studies, as well as a thorough description of the groups and any matching. In addition to reporting P values, it is important that outcome papers include the 95% confidence interval for any effect reported; this allows readers to ascertain the true range of treatment effect. When stating the percent reduction in myopia progression or axial elongation between a treatment and control group, previous studies (see Section 2.1) have reported treatment effects in the first study year that did not accrue in subsequent years; therefore, it is critical that the authors report the time period over which that reduction occurred (e.g., over 1 year or 3 years). No specific minimum percent reduction in myopia progression has been published for a treatment effect to be considered clinically meaningful. Any percent reduction threshold could vary based on multiple other factors, including duration of treatment, sample population, and study design considerations. However, some clinicians anecdotally report roughly a 40% reduction in progression over 3 years as clinically meaningful to them. That said, evidence shows that any reduction in progression can be beneficial.70 Of course, it is important to factor the relative risk of the treatment versus the reduction in risk provided by reduction in myopia. For example, a treatment with very low risk of adverse event may have a different minimum acceptable reduction than one with a higher risk of adverse event (Fig. 1). A thorough long-term, risk-benefit analysis is necessary. It is also notable that some children respond to treatment while others do not. Currently, there seems to be no way of predicting whether a particular child will or will not respond. While other ways of evaluating efficacy—for example, the percentage of children who had a reduction in myopia progression of 50% compared to the rate of progression in the control group—may provide additional information beyond the traditional mean ± SD and 95% confidence interval, any arbitrary threshold allows researchers to find a suitable analysis approach. High myopia (as defined by the IMI – Defining and Classifying Myopia Report87) could be taken as a standard way to discuss how many people avoid developing high myopia as the result of applying a particular management strategy. 
Figure 1
 
Schematic of considerations that influence the clinically meaningful effect size.
Figure 1
 
Schematic of considerations that influence the clinically meaningful effect size.
2.10 Sample Size
Sample size based on the axial length effect size with the different modalities of myopia control treatment are outlined in Table 4. In many cases, key information was missing from publications and personal communication with the principal investigator was required to gain additional statistics. 
Table 4
 
Sample Size Calculations for Different Modalities of Myopia Control Treatment Based on Axial Length Effect Size
Table 4
 
Sample Size Calculations for Different Modalities of Myopia Control Treatment Based on Axial Length Effect Size
3. Clinical Trial Outcomes and Related Instrumentation
3.1 Primary Outcomes
Clinical trials represent a crucial source of information to guide the application of basic, clinical, and translational research toward the health benefit of patients. These trials test a hypothesis following a chosen treatment. A primary outcome is arriving at a decision on the overall results of the study, specifically whether the hypothesis tested is fulfilled.88 Clinically relevant primary outcomes should relate the tested treatment directly to the patient's health and be related to disease scales. Therefore, the primary outcome of a clinical trial could be a risk/preventative factor for a disease and be sensitive enough to detect the degree of change expected from the intervention.89 Coster proposes choosing outcome measures through creation of a causal model: “The causal model makes explicit the researcher's thinking about how the intervention is expected to achieve its results—that is, what the hypothesized mechanism of change is and in which aspects of the person's life changes are most likely to be evident.”89 
Clinical trials in the research field of myopia have utilized mainly refractive error and axial length as primary outcome measures, regardless of the intervention: OK,10,1719,9092 atropine,30,47,93 or bifocal contact lenses.22,80,94 Additional secondary outcome measures, such as peripheral refraction, may be considered depending on the hypothesis being tested.28 Overall, refractive changes are highly correlated to eye growth despite the type of myopia control intervention: under-correction,95 multifocal/bifocal spectacles versus single vision spectacles,7,13,33,96,97 or bifocal contact lenses versus single vision.21 However, this is not the case in all studies.98 
Early myopia control clinical studies did not measure and monitor axial elongation,99,100 and those that used ultrasonography would have been limited by the resolution of this technique (∼0.30 D),101 making refractive error the preferred outcome measure in earlier studies. More recently, the measurement of the biometric components of the eye has become more widely included and is a key measurement in myopia control clinics, partly due to the non-invasive nature and improved resolution (∼0.03 D) of the interferometry measurements for axial length (see Section 3.1.1).101,102 Participantive refraction is more variable than autorefraction, despite being considered the gold standard for clinical refraction.103 Changes in refractive error may occur due to changes in corneal curvature, so when refractive error needs to be used as the primary outcome measure, corneal curvature should be measured to help with data interpretation.104 Overnight OK purposely alters corneal topography to target emmetropia during waking hours, so axial length can be the only primary outcome measure for the myopia control aspect of OK myopia control studies. 
The advantages of using axial elongation versus refractive error as the primary outcome measure relates to the direct relationship between the excessive growth of the myopic eye and the associated risk for posterior pole complications, although the two are strongly correlated.105108 The incidence of various myopia-related complications (such as temporal crescents, posterior staphyloma, and chorioretinal atrophy) increases in parallel with axial length.109 Highly myopic eyes (axial length ≥27 mm) can show macular Bruch's membrane defects associated with complete loss of retinal pigment epithelium and choriocapillaris, large choroidal vessels, and marked reduction of photoreceptors, which are strongly associated with increased axial length.110,111 In addition to studies in human eyes, experimental myopia induced in fish, avian, mammal, and primate eyes is also characterized by axial elongation.112120 Axial elongation of the eye triggers chorioretinal stretching and thinning of the choroid, retina, and scleral wall,121126 and increases the risk of developing posterior staphyloma109 as well as peripheral retinal changes such as lattice degeneration, pavingstone degeneration, white with or without pressure, and retinal holes and tears.127 Since even moderate amounts of myopia significantly increase the odds of vision-threatening conditions,70 the end goal of all clinical trials for myopia control should be reduction of axial elongation (associated with posterior pole complications) to have the greatest effect on myopic patients' health status. This way, a clinically relevant primary outcome is chosen directly related to patients' health and disease scales, which could be used as a risk/preventative factor for the disease. 
3.1.1 Axial Length Measurement
Axial length is typically defined as the axial distance from the anterior cornea to the retina (exact location within retina varies by technique) along the line of sight, and this ocular biometric measure is considered one of the principal biometric correlates of spherical equivalent refractive error. Numerous studies have established a strong correlation between the eye's axial length and its refractive error.105108 Myopia development and progression usually occur due to excessive axial elongation of the eye, as evidenced by the strong correlation observed between changes in refractive error (i.e., myopia progression) and changes in axial length (i.e., axial growth of the eye).7,96,128 For these reasons, measurements of the change in axial length in an individual are commonly used as the primary outcome measure of myopia clinical trials in the myopia research field. 
A range of physiological factors have been documented that lead to small, but significant, short-term/transient changes in axial length measures: diurnal variations,129,130 accommodation131,132 and changes in intraocular pressure.133,134 Clinical trials assessing axial length should therefore consider the potential influence of these factors in protocol development, providing the most reliable measures of axial length and hence comparisons within and between groups. For example, ideally, axial length measures collected at approximately the same time of day would limit the potential confounding influence of diurnal variations (although these are small)135; however, this must be balanced by retaining all participants enrolled in a clinical trial and seeing them for scheduled visits within a defined visit window. A range of instruments are currently available for assessment of axial length, and these measurement techniques can be divided into ultrasound and optical based biometry methods.101,102 
3.1.1.1 Ultrasound Biometry
Ultrasonographic methods for the measurement of intraocular distances were developed in the 1950s and 1960s,136,137 and some early studies in the myopia field used ultrasound-based techniques for assessment of axial length.138,139 Ultrasound biometry involves a transducer directing high frequency (typically 10 mHz in ocular ultrasound) pulsed sound waves into the eye and recording echoes of these waves reflected from the ocular structures. The time delay of these echoes is converted into a geometric distance through knowledge of the velocity of sound in the various ocular media. Axial length measurements from ultrasound instruments are defined as the distance from the anterior cornea to the inner limiting membrane of the retina. 
The properties of ultrasound wave require that the ultrasound transducer be in contact with the eye, either directly (in the case of applanation ultrasound) or indirectly (via immersion of the anterior eye in saline solution for immersion ultrasound) to take measurements. Studies comparing applanation and immersion ultrasound techniques typically find lower axial length readings with applanation methods, which can be attributed to compression of the cornea, leading to a reduction in the corneal thickness or anterior chamber depth (ACD) and, hence, axial length.140,141 Ultrasound axial biometry devices typically provide measurements of axial length with an accuracy of approximately 0.1 mm.140 Reports of repeatability with A-scan ultrasonography demonstrate 95% limits of agreement for test-retest repeatability in the range of ±0.2 to ±0.3 mm for measures of axial length.142144 Considering that a 0.1 mm change in axial length is the equivalent of a refractive change of ∼0.3 D, the ability of ultrasound methods to detect small magnitude changes in axial length is limited. This relatively coarse repeatability, the need for corneal anesthesia and contact with the eye, and dependence on operator expertise to achieve axial alignment of the transducer145 associated with ultrasound biometry methods have prompted development of alternative measurement techniques based on optical principles. These newer methods have largely superseded ultrasound measurements in the myopia research field. 
3.1.1.2 Optical Biometry
The limitations associated with ultrasound techniques provided the catalyst for development of optical biometry methods, based upon optical partial coherence interferometry (PCI) that provide axial length measures without the need for corneal contact.146,147 In this method, two partially coherent laser beams are directed into the eye and reflected back from the ocular tissues. Interference between the two reflected laser beams forms interference fringes with peaks corresponding to the eye's surfaces. The optical path length between these interference peaks can be converted into geometric distance based on the presumed refractive index of the ocular structures. Interferometry methods define axial length as the distance between the anterior cornea and the retinal pigment epithelium. It is worth noting that the use of an assumed average total eye refractive index will result in some overestimation of axial length when measures are collected during accommodation (an error of ∼0.02 mm was estimated to occur for measures during 10.9 D of accommodation).148 
In addition to the easier alignment and capture of the measurement due to the technique being non-contact optical methods have the added advantage of resolution (∼0.012 mm) and precision (∼0.01 mm), an order of magnitude better than ultrasound biometry.101,149,150 Commercially available devices have test-retest 95% limits of agreement typically reaching ±0.04 mm.142,143 Some optical biometers use a super luminescent diode light source (rather than a laser diode), improving the signal-to-noise ratio and thus allowing central corneal thickness, anterior chamber depth, and lens thickness to be measured at the same level of accuracy rather than employing image analysis techniques.102,151 Some recent commercial optical biometers combine highly accurate and repeatable PCI measurement of axial length with a Scheimpflug camera for assessing anterior eye biometry and a Placido disc corneal topographer.152155 
Optical coherence tomography (OCT) is also utilized to measure anterior eye biometry, but was originally developed for cross-sectional imaging of the posterior segment of the eye. Fourier-domain OCT methods provide high resolution cross-sectional and volumetric images of the posterior eye with the ability to precisely resolve individual retinal layers at an imaging depth of a few millimeters.156 Since the development of Fourier-domain OCT, a number of methods and prototype devices have been developed utilizing a range of different approaches to encompass whole eye OCT imaging and axial length measurements.157160 These devices provide rapid high-resolution measures of axial length, with precision comparable to other optical methods of axial length measurements.161163 The advantage of this OCT imaging approach is that these devices provide cross-sectional images of the eye's component structures (cornea, crystalline lens, and retina), providing additional biometric measures of central corneal thickness, lens thickness, and anterior chamber depth, thereby allowing measurement alignment and localization of ocular interfaces to be more easily verified (with reference to the cross-sectional B-scan image) than are PCI-based methods. 
The non-contact measurements, ease of alignment, and high precision measures possible with optical biometry methods, make them ideal for application to clinical trials in the myopia field. These measurement techniques provide the precision required to detect small magnitude differences and changes in axial length in clinical trials. As outlined, there are currently a number of optical biometry devices commercially available and, from the point of view of the precision of axial length measures, most devices exhibit similar performance. One drawback of optical biometry devices (compared to ultrasound methods) is that difficulties can be encountered in providing reliable measures of axial length if dense cataracts are present,164 but this issue is rarely encountered in the myopia research field given that the majority of clinical trials enroll young participants with clear ocular media. 
3.1.2 Refractive Error Measurement
In young children, interpretation of refractive error is complicated by potential errors in measuring refractive state due to the confounding of this measurement due to the influence that accommodation can have on this measurement. The importance of controlling accommodation becomes apparent when comparing measured refractive state with and without cycloplegia. Analyzing a sample of 6017 right eyes of children aged 4 to 15 years, non-cycloplegic refractions were found to be 0.63 ± 0.65 D more myopic than cycloplegic refractions.165 Twelker and colleagues found similar differences in infants (0.89 ± 0.66 D).166 These results indicate that noncycloplegic refractions may overestimate myopia in infants and children; since cycloplegic refractions are indeed a necessity of any myopia control study which has refractive error as a measurement outcome, most studies determine refractive error as part of their inclusion criteria using cycloplegic autorefraction (n = 17 of studies in Table 1), although this aspect of the methodology is not always recorded. 
As discussed in section 2.6. either 1% cyclopentolate or 1% tropicamide may be utilized, each with their positives and negatives. On average, one drop of 1% tropicamide produced 0.14 D more myopic refractive error measures than one drop of 1% cyclopentolate.46 Yazdani and colleagues167 found a similar amount in a meta-analysis of six studies, with tropicamide refractions 0.175 D more myopic. Mutti and colleagues also found this characteristic (0.20 ± 0.30 D) in a prospective study.168 As between-participant and between-race differences in the myopic bias of refractions are generally larger than many of the myopic changes reported in myopia control studies,21,24,94,169 it is imperative that any study assessing a myopia control device employ the same cycloplegic procedures for each measure of refractive error throughout. 
The reported impact of cycloplegic agents on distance refractive errors reflect well documented differences between participants in drug efficacy.170 Specifically, dark irises are typically associated with reduced drug efficacy.45,171 Also, because the time course of cycloplegia and mydriasis can differ,45,171 pupil size should not be used as an indicator of cycloplegia. It is recommended that clinical trials employing cycloplegic refractions ensure that refractions are performed at a fixed time after drug instillation (e.g., 30 or 60 minutes) and that accommodative status is assessed prior to refractive error measurements being taken. Tropicamide has been reported to have a maximal cycloplegic effect at 30 minutes, whereas the maximal cycloplegic effect of cyclopentolate is reported to be 60 minutes. Given a faster maximal effect and similar reported cycloplegic effect—despite the possibly increased cycloplegia of 1% cyclopentolate—most myopia control studies have utilized 1% tropicamide to obtain their cycloplegic refractions,21,24 whereas others have used both 1% tropicamide and 1% cyclopentolate.172 
Although autorefractors still may have repeatability of ∼±0.21 D,173 which could encompass a good percentage of the roughly 0.30 to 0.50 D per-year treatment effect24,94,169 being targeted, autorefractors typically exhibit higher precision than do participantive refractions (smaller coefficient of repeatability)174 and minimize unconscious investigator bias. Because of these aspects, only objective refractions should be used in myopia control studies. Furthermore, to minimize variability due to residual accommodation and instrument myopia, autorefractors should be open-field. To assure they provide an accurate measure, they should be validated across their measurement range.175177 Since myopia control studies often involve multiple comparisons across several years, instrument stability is essential across the entire duration of the study. If possible, this can be accomplished by initial and continued instrument calibration at specified time frequencies during data collection according to the instrument manufacturers' recommendations. Specially designed model eyes can be used for calibration.178,179 
As the standard clinical refraction is designed to generate a single end point, it can be mistakenly assumed that an eye has a single refractive state. However, due to ocular aberrations, refractive state can vary significantly across the pupil.180 Therefore, refraction methods that employ a known pupil location, repeatable across time, are preferred. For example, eccentric photorefraction and retinoscopy can have their results affected by aberrations in the pupil margins,181,182 while participantive refractions are biased toward the pupil center.183 Objective methods that employ a known measurement aperture that can be repeatedly located in (or close to) the pupil center are recommended. 
3.2 Secondary Outcomes
3.2.1 Patient Reported Outcomes
Most myopia control clinical trials include primary outcome measures that can be objectively measured (such as an autorefractor measure of refractive state or biometric measures of axial length; see section 3.1). However, there are significant insights to be gained from the child's wearing experience, effectiveness of the treatment and understanding the results obtained, by simultaneously capturing child (participant) or parent-reported outcomes. Many measures are common to those of typical contact lens trials, such as assessing comfort, lens awareness, ease of care, wear time and frequency of problems.184,185 As myopia control strategies often employ multi-zone optics that may create ghosting or doubling of images,186188 other informative patient-reported outcomes may include visual quality189 while performing different tasks (such as reading, computer use, and night vision) and the time to perform these tasks.184,185 Any participants enrolled in a clinical trial who discontinue treatment should be queried about the reason for the discontinuation. 
In clinical trials, the reliability of compliance aspects could be assessed by asking both child and parent/caregiver separately. The agreement between child and parental/caregiver responses is not known, especially as it relates to contact lens use (such as hours of use) and satisfaction. However, results of behavioral research suggest a low degree of agreement, and differential levels of agreement believed to be associated with transitions in age.190 It appears that agreement between parent and child responses varies with parent experience. Specifically, in a meta-analysis of 19 studies (including health-related quality-of-life instruments), parents with the condition being studied underestimate the child's responses, whereas those without the condition reported higher quality of life than did the child.191 This result may depend on the specific questions or health-related quality-of-life instrument. Until more information is available, querying both child and parent/caregivers is recommended, as each group will provide valuable information (such as how often a parent has to assist with insertion of a contact lens). 
3.2.2 Assessing Treatment Compliance
It is widely accepted that compliance with treatment is an important aspect contributing to the outcome and validity of results in any clinical trial.192,193 In general, compliance in clinical studies relates to the adherence with the prescribed regimen (such as contact lens wear in a myopia control study investigating the impact of OK). However, there are many other aspects of compliance, including study visit compliance, adhering to study procedures, and reporting adverse events. 
Literature relating to the impact of compliance on myopia control clinical trials is sparse. Comparisons can be made with clinical trials in the medical field, where it is known that non-compliance may be underestimated.194 Assessment of compliance is affected by how it is measured. For example, a clinical study involving an anti-depressant drug estimated a compliance rate of 70% based on evidence of medication in blood samples drawn from the participants, as compared to 92% using pill count as the measure of compliance.195 It has been estimated that up to 30% of clinical trial participants are untruthful about medication compliance and may be throwing away investigational product prior to study visits.196,197 This is relevant to pharmaceutical studies as well as studies involving contact lenses, in which compliance can be assessed by the number of lenses used during a specific time period. Participants could be required to bring all unused product to each appointment so the number of remaining lenses can be counted and compliance based on that count; however, this relies on compliance with replacement frequency and that no product is discarded due to damage. It has also been noted that compliance in clinical studies is generally better in the first few months of a study and drops off thereafter to a level similar to compliance in clinical practice. For example, in a study on children with mild asthma, adherence to the medication dosage prescribed in the clinical study was 75% at the 3-month time point but dropped to 53% after 9 months.198 
The most common approach to reporting compliance with prescribed practices (such as taking medication or using a device on a regular basis) is to collect data retrospectively on participant activity at the scheduled study visits. This may result in an inaccurate estimation of information from the participant or parent, leading to incorrect data, or data that has to be excluded because the reported information could not be assumed accurate.199 Participants may not provide accurate reporting of behavioral information, especially when being asked to recall from a considerable time period prior to the study visit.200 Participants who understand the importance of compliance may choose to modify responses or behaviors to appear compliant. 
In an attempt to minimize errors due to recall, a simple method of collecting data on activities outside the study visits is often achieved by means of a questionnaire/diary (such as nightly or weekly between study visits). There is strong evidence to support the use of modern technology (electronic methods) to collect such data. Stone and colleagues reported that despite participants reporting 90% adherence with that written in their paper diaries, the actual rate was as low as 11%. In switching to an electronic diary, the participants are aware that the information is date and time stamped, increasing adherence to 94% and reducing the risk of participants exaggerating their adherence to study protocols.201 Myopia control studies are typically lengthy, lasting for several years, with a significant time period between appointments. In studies involving contact lenses, participants are generally required to wear lenses for a minimum amount of time and are often required to self-report their wearing schedule (hours per day and days per week). This can be undertaken at periodic intervals between study visits or can be self-reported at each study visit. Reminders to participants, for example, to complete diaries about activities or to ensure that they wear their device for a certain number of hours or days per week, should promote compliance with study protocols. 
In the healthcare field, one simple method of electronic reporting is possible through text messaging (SMS) participants. SMS has been found to be both cost effective and beneficial, with the effectiveness of electronic reminders on compliance with medical treatment being well documented. Specifically, Lester and colleagues demonstrated an improvement in HIV treatment outcomes with patients who received SMS support, and Miloh and colleagues203 demonstrated significant medication adherence and a reduction in rejection episodes when text messaging reminders were sent for pediatric recipients of liver transplants. A systematic literature review by Vervloet et al.204 confirmed evidence for short-term effectiveness of SMS electronic reminders, but the long-term effect remains unclear.202204 Specifically related to optometric clinical trials, Morgan reported up to 93% of participants responding within a 30-minute period of a specified time point using SMS messaging, and Woods and colleagues demonstrated a 97.5% response rate to requests for data from participants generated via smartphone.205,206 
Gamification is defined as the process of adding games or game-like elements to something (such as tasks) to encourage participation.207 Gamification within the healthcare field is increasing in popularity and has a positive influence on health behaviors.208210 Gamification has been explored as an option for increasing recruitment, retention, and compliance in clinical trials. Rowbotham and colleagues211 demonstrated that interactive media improved comprehension of research study procedures and risks. Gamification provides a process of rewarding participants for completing tasks, for example, diary completion. Virtual rewards take the form of points or levels and helps drive competitive behavior. In one study using gamification technology, medication adherence increased from 58% to 95%.212 In a clinical trial setting, gamification could improve compliance, resulting in more robust data. 
The emergence of wearable technology into the clinical research space is changing the way in which clinical data can be obtained. Health and wellness devices are commonly worn and are a widely accepted accessory. In 2013, there were over 97,000 mobile health apps available to consumers.213 By 2017, this number increased to 325,000 apps. It has been estimated that by 2020, there will be 4 million patients using remote monitoring health technology.214 For the purposes of myopia control studies, information that can be captured by wearable technology includes aspects such as time exposed to certain light levels/spectrums, working distances, and physical activity. There are several examples in the literature of wearable technology being used to monitor light levels, and data obtained from such devices can support assessment of treatment compliance in studies where treatment relates to time spent outside.215,216 
Participant recruitment and retention are critical to the success of clinical trials and to the validity of the results. Participants are generally required to undergo more clinical procedures than they would in a non-research setting, such as being required to complete questionnaires and attend more frequent appointments. It is important from the outset that the participant—and in many cases the parent/guardian—understands what is required of them for the period of the study. An understanding of expectations will likely result in better compliance with the study protocol and better retention of participants. Where possible, clinical trials should be as participant-centered as possible, for example, ensuring that appointment times are convenient for participants. In the case of studies with children, having appointments available after school hours or on weekends may be necessary.217,218 
Consent forms (or parental permission forms and child assent forms) that are provided ahead of enrollment should be simple and written in language that participants can understand since there needs to be an appreciation of expectations of compliance to study protocol and what would constitute non-compliance, along with the importance of reporting non-compliance. It is recommended that informed consent documents read by adults be written at or below Grade 8 level.219 Adults typically read three to five levels lower than the school grade level they completed.220,221 When children are recruited into clinical studies, an “assent form” is used for the child, and it is imperative that the assent be written in language appropriate for the age of recruitment. Participants with a poorer reading grade level than the level of text in the informed consent form may not understand all of the content of the document.222 During the recruitment (and follow-up visits), it is important that the participant trusts the researcher, understands that reporting non-compliance is a vital part of study data collection, and that this does not reflect poorly on the participant. Study participants may not want to let the researcher know that they have been non-compliant, as this may “disappoint” the researcher or result in them being withdrawn from the study. 
3.3 Exploratory Outcomes
While axial length and refractive error are well established as primary outcome measures of myopia control trials, an increasing number of exploratory outcomes have been adopted to aid in the prediction of efficacy for individuals, to better understand the mechanism of control, or to investigate safety aspects. These exploratory outcomes may sometimes be specific to testing different hypotheses associated with different myopia control approaches: peripheral refraction, accommodative changes, ocular alignment, and posterior segment imaging to optical myopia control techniques; accommodative changes and pupil size to current pharmaceutical approaches; outdoor activities to myopia control environmental policies; and anterior segment imaging and tissue biomechanics to OK. 
3.3.1 Peripheral Refraction
In 1801, Thomas Young223 estimated the astigmatic image shells in a model of his own eye. Hoogerheide and colleagues224 suggested that certain patterns of peripheral refraction—involving the peripheral retina being less myopic or more hyperopic than the central retina—could predispose an eye to development of myopia. Several studies on different animal models have since shown that image quality on the peripheral retina can regulate ocular growth in chickens,113,115 monkeys,225229 and guinea pigs120 and that an eye with peripheral hyperopia continues to grow even though the central image is well-focused on the fovea.229 The review by Wallman and Winawer230 has inspired many investigations of human peripheral refraction, and the interest in refraction has extended to include higher-order aberrations. Relative peripheral refraction is a surrogate for eye shape, but it does not describe the optical experience thought to regulate eye growth. 
As described earlier for central (foveal) refraction, the peripheral refraction is preferably measured with accommodations paralyzed to avoid changes in the optical profile (see review by Lundström and Rosén231). Furthermore, it is practical to express peripheral refractions in terms of mean sphere and two astigmatic components232:  
\(\def\upalpha{\unicode[Times]{x3B1}}\)\(\def\upbeta{\unicode[Times]{x3B2}}\)\(\def\upgamma{\unicode[Times]{x3B3}}\)\(\def\updelta{\unicode[Times]{x3B4}}\)\(\def\upvarepsilon{\unicode[Times]{x3B5}}\)\(\def\upzeta{\unicode[Times]{x3B6}}\)\(\def\upeta{\unicode[Times]{x3B7}}\)\(\def\uptheta{\unicode[Times]{x3B8}}\)\(\def\upiota{\unicode[Times]{x3B9}}\)\(\def\upkappa{\unicode[Times]{x3BA}}\)\(\def\uplambda{\unicode[Times]{x3BB}}\)\(\def\upmu{\unicode[Times]{x3BC}}\)\(\def\upnu{\unicode[Times]{x3BD}}\)\(\def\upxi{\unicode[Times]{x3BE}}\)\(\def\upomicron{\unicode[Times]{x3BF}}\)\(\def\uppi{\unicode[Times]{x3C0}}\)\(\def\uprho{\unicode[Times]{x3C1}}\)\(\def\upsigma{\unicode[Times]{x3C3}}\)\(\def\uptau{\unicode[Times]{x3C4}}\)\(\def\upupsilon{\unicode[Times]{x3C5}}\)\(\def\upphi{\unicode[Times]{x3C6}}\)\(\def\upchi{\unicode[Times]{x3C7}}\)\(\def\uppsy{\unicode[Times]{x3C8}}\)\(\def\upomega{\unicode[Times]{x3C9}}\)\(\def\bialpha{\boldsymbol{\alpha}}\)\(\def\bibeta{\boldsymbol{\beta}}\)\(\def\bigamma{\boldsymbol{\gamma}}\)\(\def\bidelta{\boldsymbol{\delta}}\)\(\def\bivarepsilon{\boldsymbol{\varepsilon}}\)\(\def\bizeta{\boldsymbol{\zeta}}\)\(\def\bieta{\boldsymbol{\eta}}\)\(\def\bitheta{\boldsymbol{\theta}}\)\(\def\biiota{\boldsymbol{\iota}}\)\(\def\bikappa{\boldsymbol{\kappa}}\)\(\def\bilambda{\boldsymbol{\lambda}}\)\(\def\bimu{\boldsymbol{\mu}}\)\(\def\binu{\boldsymbol{\nu}}\)\(\def\bixi{\boldsymbol{\xi}}\)\(\def\biomicron{\boldsymbol{\micron}}\)\(\def\bipi{\boldsymbol{\pi}}\)\(\def\birho{\boldsymbol{\rho}}\)\(\def\bisigma{\boldsymbol{\sigma}}\)\(\def\bitau{\boldsymbol{\tau}}\)\(\def\biupsilon{\boldsymbol{\upsilon}}\)\(\def\biphi{\boldsymbol{\phi}}\)\(\def\bichi{\boldsymbol{\chi}}\)\(\def\bipsy{\boldsymbol{\psy}}\)\(\def\biomega{\boldsymbol{\omega}}\)\(\def\bupalpha{\unicode[Times]{x1D6C2}}\)\(\def\bupbeta{\unicode[Times]{x1D6C3}}\)\(\def\bupgamma{\unicode[Times]{x1D6C4}}\)\(\def\bupdelta{\unicode[Times]{x1D6C5}}\)\(\def\bupepsilon{\unicode[Times]{x1D6C6}}\)\(\def\bupvarepsilon{\unicode[Times]{x1D6DC}}\)\(\def\bupzeta{\unicode[Times]{x1D6C7}}\)\(\def\bupeta{\unicode[Times]{x1D6C8}}\)\(\def\buptheta{\unicode[Times]{x1D6C9}}\)\(\def\bupiota{\unicode[Times]{x1D6CA}}\)\(\def\bupkappa{\unicode[Times]{x1D6CB}}\)\(\def\buplambda{\unicode[Times]{x1D6CC}}\)\(\def\bupmu{\unicode[Times]{x1D6CD}}\)\(\def\bupnu{\unicode[Times]{x1D6CE}}\)\(\def\bupxi{\unicode[Times]{x1D6CF}}\)\(\def\bupomicron{\unicode[Times]{x1D6D0}}\)\(\def\buppi{\unicode[Times]{x1D6D1}}\)\(\def\buprho{\unicode[Times]{x1D6D2}}\)\(\def\bupsigma{\unicode[Times]{x1D6D4}}\)\(\def\buptau{\unicode[Times]{x1D6D5}}\)\(\def\bupupsilon{\unicode[Times]{x1D6D6}}\)\(\def\bupphi{\unicode[Times]{x1D6D7}}\)\(\def\bupchi{\unicode[Times]{x1D6D8}}\)\(\def\buppsy{\unicode[Times]{x1D6D9}}\)\(\def\bupomega{\unicode[Times]{x1D6DA}}\)\(\def\bupvartheta{\unicode[Times]{x1D6DD}}\)\(\def\bGamma{\bf{\Gamma}}\)\(\def\bDelta{\bf{\Delta}}\)\(\def\bTheta{\bf{\Theta}}\)\(\def\bLambda{\bf{\Lambda}}\)\(\def\bXi{\bf{\Xi}}\)\(\def\bPi{\bf{\Pi}}\)\(\def\bSigma{\bf{\Sigma}}\)\(\def\bUpsilon{\bf{\Upsilon}}\)\(\def\bPhi{\bf{\Phi}}\)\(\def\bPsi{\bf{\Psi}}\)\(\def\bOmega{\bf{\Omega}}\)\(\def\iGamma{\unicode[Times]{x1D6E4}}\)\(\def\iDelta{\unicode[Times]{x1D6E5}}\)\(\def\iTheta{\unicode[Times]{x1D6E9}}\)\(\def\iLambda{\unicode[Times]{x1D6EC}}\)\(\def\iXi{\unicode[Times]{x1D6EF}}\)\(\def\iPi{\unicode[Times]{x1D6F1}}\)\(\def\iSigma{\unicode[Times]{x1D6F4}}\)\(\def\iUpsilon{\unicode[Times]{x1D6F6}}\)\(\def\iPhi{\unicode[Times]{x1D6F7}}\)\(\def\iPsi{\unicode[Times]{x1D6F9}}\)\(\def\iOmega{\unicode[Times]{x1D6FA}}\)\(\def\biGamma{\unicode[Times]{x1D71E}}\)\(\def\biDelta{\unicode[Times]{x1D71F}}\)\(\def\biTheta{\unicode[Times]{x1D723}}\)\(\def\biLambda{\unicode[Times]{x1D726}}\)\(\def\biXi{\unicode[Times]{x1D729}}\)\(\def\biPi{\unicode[Times]{x1D72B}}\)\(\def\biSigma{\unicode[Times]{x1D72E}}\)\(\def\biUpsilon{\unicode[Times]{x1D730}}\)\(\def\biPhi{\unicode[Times]{x1D731}}\)\(\def\biPsi{\unicode[Times]{x1D733}}\)\(\def\biOmega{\unicode[Times]{x1D734}}\)\begin{equation}{\rm{M = S + C/2}}\end{equation}
 
\begin{equation}{{\rm{J}}_{{\rm{180}}}}\ {\rm{ = - }}\left( {{\rm{C/2}}} \right){\rm{cos}}\left( {{\rm{2\alpha }}} \right)\end{equation}
 
\begin{equation}{{\rm{J}}_{{\rm{45}}}}\ {\rm{ = - }}\left( {{\rm{C/2}}} \right){\rm{sin}}\left( {{\rm{2\alpha }}} \right)\end{equation}
with S/C × α being the sphere/cylinder/axis format. In the M, J180, J45 format, statistical analysis is easy to perform and at any appropriate time conversion can be reverted back to S/C × α format. As well as absolute values, relative peripheral refraction is often specified in which central M is subtracted from peripheral refraction M values.  
Studies of the peripheral refraction in human eyes have shown a consistent difference at the group level between eyes of different central refractive states; myopic eyes tend to have a more hyperopic relative peripheral refraction (typically around +1.00 D in the 30° temporal visual field) than do emmetropic and hyperopic eyes (typically between 0 and −1.00 D), but the variation between individuals can be large.231 These differences may be largely a consequence of the excessive eye growth, causing myopic eyes to be more elongated relative to emmetropic eyes,106 and the hypothesis that peripheral refraction of the uncorrected eye may be used to predict which children might develop myopia224 has not been supported in clinical studies.233236 
It is difficult to give criteria for differences or changes in peripheral refraction pattern that could be considered clinically significant. To the best of our knowledge, no such criteria have been suggested. Several studies have made group or treatment comparisons at individual field locations, mostly along the horizontal visual field and at angles from ±10° to ±40°. Note that relative effects will be more pronounced as one moves further from fixation. Values have high interparticipant variation in the region of 15° into the temporal field, corresponding to the optic disk on the retina; these are usually discounted in analysis. A related issue is how far from fixation that peripheral refraction would be considered relevant to development and progression of myopia; in this regard, Mathur and Atchison237 suggested an outer horizontal meridian limit of 40° from fixation as beyond that angle many adult emmetropes had a pattern of relative peripheral hyperopia. A relevant angle could be 30° in the temporal visual field, in which myopic and emmetropic eyes tend to be separated by less than 2.00 D, as mentioned above. Therefore, 2.00 D would set the upper limit for a criterion on differences in relative peripheral refraction of practical significance. The lower limit for a criterion could be set by depth-of-field, which increases with eccentricity as both astigmatism and higher-order aberrations increase in magnitude off-axis231; at 30° temporal visual field astigmatism gives a Sturm's interval of around 1.00 to 2.00 D. In this context, it should also be noted that the most common design of optical corrections for myopia prevention cause further increases in the depth of field.238 With this reasoning, a criterion on differences in relative peripheral refraction of practical significance at 30° temporal visual field could be in the order of 0.50 to 1.00 D. However, it may be more relevant to the emmetropization process to compare different peripheral field meridians with each other instead of with the fovea, such as asymmetries between the temporal and the nasal visual fields.239,240 
In addition to uncorrected peripheral refraction, there is also interest in measuring corrected peripheral refraction (peripheral defocus) after OK and while wearing a contact lens. Myopic peripheral defocus has been hypothesized to slow myopia progression. Although relative peripheral refraction of the uncorrected eye may not be associated with myopia onset or progression (see previous), some longitudinal studies have reported an association between peripheral refraction while wearing correction and myopia progression.94,241 Standard spectacles can increase peripheral hyperopic defocus,37,39,242 while multifocal spectacles and contact lenses can cause myopic peripheral defocus.241,243,244 The use of autorefraction to determine the effect of a particular optical device on peripheral defocus may be of interest as a secondary outcome in studies trying to determine factors that may predict which eyes respond best to a myopia control lens design. Standardized measurement methods are needed in such studies. 
Peripheral refraction has been determined by several methods, including variations of participantive refraction, retinoscopy, manual optometers (such as the Zeiss coincidence and parallax optometers), the double-pass point-spread function, photorefractors, autorefractors, and aberrometers.231,245 Participantive refraction is challenging because of reduced retinal function making judgments difficult, so there are few reports.237,246248 Retinoscopy, which has been used since the late 19th century,249 requires considerable examiner skill and is not as repeatable as autorefraction.250 
In applications of these techniques, the eye is often rotated to align the measurement axis of the instrument with the desired visual field location. It is common to set up external fixation targets along the horizontal visual field for open-field autorefractors. However, a large eye rotation will alter muscular stress as well as eyelid pressure on the eyeball, potentially causing optical changes,251253 although such changes have not been noted in more recent studies.254256 In the case of contact lenses, it should also be noted that El-Nimri and Walline257 found that eye movements can cause shifts in soft contact lenses by more than 0.5 mm, and thus have the potential to affect peripheral refraction measurements. It is recommended that (where possible and without slowing measurement time) eye movements should be limited during peripheral refraction testing, especially when measuring at large angles. 
The main instruments used to determine refraction in the peripheral visual field in the last 15 years are commercial open-field autorefractors, mainly Shin-Nippon (Osaka, Japan), Grand Seiko instruments (Mahwah, NJ, USA), and Hartmann-Shack wavefront sensors (such as Thorlab, Inc., Newton, NJ, USA), while the latter can also be used to determine higher-order aberrations. A few laboratories have developed “automated” instruments to shorten measurement time.258260 There are issues associated with each type of instrument for peripheral measurement, for which they were not designed: 
3.3.1.1 Autorefractors
The Shin-Nippon and Grand-Seiko instruments record refraction corresponding to an annulus in the pupil of 2.3 to 3.0 mm177; imprecise positioning over refractive corrections with narrow optical zones could lead to erroneous measurements, although consistency has been demonstrated with accurate placement.261 When there are rapid changes in the optics across the field, the measured refraction does not keep pace. The extreme case is when there is a discrete change in the optics, such as occurs with concentric bifocal intraocular lenses and contact lenses (a central zone is responsible for distance vision and a peripheral zone is responsible for near vision, or vice versa). Other examples are when corneal shape is altered by refractive surgery262,263 or OK.264,265,266 As long as it is understood that there is a lag in refraction changes into the periphery, this is not a major concern. When planning clinical trials, it is also important to recognize that repeatability of autorefraction declines when further measurements are made in the periphery in both normal eyes173 and in eyes that have undergone OK.172 
The majority of peripheral refraction measurements with the instruments have been along the horizontal meridian, with few measurements along the vertical meridian239,267 and only one study has considered oblique meridians.268 Osuagwu and colleagues269 found that higher-order aberrations, such as coma, affect the shape of the retina image for oblique meridians, consequently affecting refraction measurement along these meridians. While this was investigated with the Shin-Nippon/Grand Seiko SRW-5000 with an analyzing pupil annulus of 3.0 mm diameter, and may be of less consequence with newer versions such the Shin-Nippon NVision K-5001/Grand Seiko WR-5100K with a smaller 2.3 mm analyzing pupil, the authors recommended that autorefractors should not be used to determine peripheral refraction along oblique meridians and advised that instruments be validated before being used outside the scope intended by the manufacturer. 
3.3.1.2 Wavefront Sensors
The size and shape of the pupil used in analysis is important. The pupil is mostly circular on-axis, but when viewed off-axis, it becomes elliptical in shape, making traditional methods of power determination utilizing a Zernike fitting problematic.237 Alternatives in dealing with this approach and using a Zernike fit include using an elliptical pupil shape stretched along its minor axis to become a circle, or using a circular pupil whose diameter matches either the larger or smaller dimensions of the elliptical pupil. These different approaches will give different errors and estimations of aberrations. Aberrations, although with correct manipulation, they will give similar estimates of refraction from even-order Zernike aberration coefficients. Comparison and conversion code for the different estimations were given by Lundström, Gustafsson, and Unsbo.240 Based on simplicity of approach, possible departures of off-axis pupils from ellipticity and ease of understanding, a circular pupil approach based on a diameter that fits within the actual pupil should be adopted.231,270 Alternatively, as this approach may bias the results to the central optics—of possible importance when measuring through center-surround zonal lenses—Zernike fitting could be avoided all together by either determining refractive power based on the local slope/zonal integration271 or by calculating the wavefront vergence based on the raw slope measured by the instrument.272 
Charman and colleagues270 argued that visual field (such as superior visual field) rather than a retinal (such as inferior retina) reference be used when describing peripheral refraction measures. Specifically, the angles associated with each measure and distances from fixation should be specified in terms of object space rather than within the eye. For sign convention, most peripheral refraction studies have assigned positive values to the nasal visual field and the superior visual field.231 It has been suggested that the ophthalmic optics convention of determining visual field meridian in terms of an anticlockwise angle (from the right side when viewing a patient's eye) be adopted, in which case the eccentricity does not require a sign.270 
Peripheral aberration coefficients across the visual field show considerable mirror symmetry between right and left eyes.269,273 In a pooled data set (such as when combining temporal visual data of right and left eyes and combining nasal visual data of right and left eyes), the coefficients with negative correlations between right and left eyes require sign changes for left eyes. The correction needed is that used for positions in the pupil for on-axis aberrations as specified in the ISO standard for ophthalmic wave aberrations.274 Specifically, signs of left eye coefficients are altered for which the Zernike polynomial functions Display Formula\(Z_n^m\) (m = radial degree and n = azimuthal degree) have negative, even m-indices or positive, odd m-indices, such as for Display Formula\(C_2^{ - 2}\), Display Formula\(C_3^1\), Display Formula\(C_3^3\), Display Formula\(C_4^{ - 4}\), and Display Formula\(C_4^{ - 2}\) (the coefficients for oblique astigmatism, coma, trefoil, and oblique secondary astigmatism, respectively). 
Another consideration is the same issue described above relating to autorefractors regarding the effect of rapid spatial changes in the optics during refraction measurements. In the case of “regular” changes such as OK, the analysis pupil size can be varied to more clearly show changes in refraction; for example, analyzing with a 2-mm pupil rather than a 3-mm pupil will show more rapid changes and better reflect changes in corneal surface shape. However, there will be problems with discrete changes. Figures 2 and 3 show spot diagrams and wave aberration maps for a theoretical example of a distance-center bifocal lens combined with a model eye, in which the center and peripheral contact lens zones contribute in varying amounts to imaging and the determination of aberrations as the horizontal visual field angle changes. How a particular instrument deals with this depends on its sampling density, its algorithms for determining transverse aberrations, and Zernike wave aberration fitting. Clearly, there is no oblique astigmatism here, but one paper has reported considerable, artifactual, oblique astigmatism (J45) for a distance-center lens rising to ≈0.70 D at about 25° horizontally from the center of the field.275 The problem is the inadequacy of fitting Zernike aberration polynomials with these lenses with multiple or discrete zones. A partial solution for measuring refractions through such lenses is to determine refractions from Zernike circular polynomials obtained using small pupils (such as 1 mm) and ignore discontinuities corresponding to zone boundaries. Alternatively, more elaborated image quality metrics than those calculated directly from the Zernike coefficients could be used when analyzing the peripheral optical effect of these lenses. Rosén and colleagues238 used the area under the MTF curve for a 4-mm pupil diameter, which provides a more complete description of retinal image quality, reflecting the ambiguity of defining the far point with a discrete change in refraction over the pupil. Additionally, as described, refractive power could be obtained based on calculations from the local slope/zonal integration271 or by calculating the wavefront vergence based on the raw slope measured by the instrument.272 
Figure 2
 
Spot diagrams for a distance-center bifocal contact lens combined with the Navarro schematic eye,276 as a function of horizontal visual field angle. Out of the eye raytracing, distance power 0D, addition +2D, center zone diameter 2 mm, refractive index 1.43, pupil size 3 mm, back surface of contact lens is that of the cornea at 7.72 mm. Drawn with Zemax OpticStudio 16.5 SP1 (Zemax, LLC, Kirkland, WA, USA).
Figure 2
 
Spot diagrams for a distance-center bifocal contact lens combined with the Navarro schematic eye,276 as a function of horizontal visual field angle. Out of the eye raytracing, distance power 0D, addition +2D, center zone diameter 2 mm, refractive index 1.43, pupil size 3 mm, back surface of contact lens is that of the cornea at 7.72 mm. Drawn with Zemax OpticStudio 16.5 SP1 (Zemax, LLC, Kirkland, WA, USA).
Figure 3
 
Wave aberration maps in the exit pupil plane for a distance-center bifocal contact lens combined with the Navarro schematic eye. Conditions are the same as for Figure 2. Drawn with Zemax OpticStudio 16.5 SP1 (Zemax, LLC).
Figure 3
 
Wave aberration maps in the exit pupil plane for a distance-center bifocal contact lens combined with the Navarro schematic eye. Conditions are the same as for Figure 2. Drawn with Zemax OpticStudio 16.5 SP1 (Zemax, LLC).
3.3.2 Accommodation Changes With Optical Devices
3.3.2.1 Lag of Accommodation
Accommodation lag is usually measured participantively with MEM or Nott retinoscopy, or objectively277 with an open-field autorefractor81,278281 or wavefront aberrometer,282 with the participant viewing through their distance correction (or spherical equivalent lenses). The lag of accommodation is calculated as the change in measured refraction from distance viewing subtracted from the anticipated accommodative demand related to the target distance.28,282 If the measurement of accommodative response is derived from aberrations over a particular pupil size, then, for the measurements to be accurate, the change in the individual's eye focus should be weighted to their dynamic pupil changes.283 To fully drive the accommodative system, the target should be high contrast and close to the maximal visual acuity threshold.284 Alternatives include using fused cross-cylinders,86 monocular estimate method,285 and Nott retinoscopy, all of which are less accurate and repeatable.277 
3.3.2.2 Dynamic Changes of Accommodation
Accommodation is a dynamic process and allows pre-presbyopes to focus across a range of distances. Dynamic changes of accommodation can be measured with open-field autorefractors (including photoretinscopy)286288 and aberrometers,289 but this has not been adopted in current myopia control studies. However, dynamics of accommodation will affect the peripheral retinal image focus, which could impact on the treatment effect if based on the peripheral refraction hypothesis. 
3.3.3 Ocular Alignment
While most bifocal or progressive multifocal spectacle studies have reported only minimal reductions in myopia progression, larger reductions in progression have been reported in children with nearpoint esophoria or accommodative dysfunctions.96,290 Multifocal contact lenses worn by children can induce exophoria, increasing with accommodative demand.79 OK causes minimal effects on ocular alignment,291 and a link between OK or pharmacological treatments for myopia control has not been reported. These results indicate some potential benefit of monitoring heterophoria either upon inclusion in a study or during the course of the study. 
Heterophoria has been assessed in myopia control treatment evaluations in a variety of ways, including alternating cover test,21,280,292,293 Howell-Dwyer near phoria card,33,294,295 Maddox wing/rod,293,296 prism dissociation,81 and von Graefe and modified Thorington techniques.79,83,297 Different free-space heterophoria measuring techniques do not give equivalent values.298 The modified Thorington technique (a tangent scale technique for assessing dissociated phoria) has been shown to be the most repeatable of the established techniques for phoria assessment, with good inter- and intra-examiner reliability.298,299 
3.3.4 Pupil Size
Pupillometry is a critical measure in most myopia clinical trials due to the limitation of the pupils on the transfer of the effects of optical interventions onto the retina,300 or to assess the adverse muscarinic receptor effect of myopia control drugs.82 Pupil size is also critical in modeling ocular aberrations (see “Clinical Trial Outcomes and Related Instrumentation: Primary Outcomes”). Pupil size can be estimated participantively and its dynamics checked with a light source82 but is better measured objectively using dedicated pupillometers,30,47,301,302 some biometers303 or aberrometers/topographers.304 Pupil size varies with task and light levels, so it is complicated to analyze and report. However, measurements are not often reported. 
3.3.5 Outdoor Activity/Light Levels
The rapid increase in myopia prevalence seen over the last few decades305 implicates a change in the environment as the primary causal agent for the current global myopia epidemic. However, the obvious geographic and racial differences in reported myopia prevalence and severity (such as very high prevalence, early onset, and high levels in East Asia), and the familial clustering of myopia306309 are consistent with genetics playing a significant role. Increased levels of myopia in racial subgroups within racially mixed societies, such as Australia and Singapore,310312 are also consistent with genetics playing a role. The hybrid hypothesis proposes that environmental changes over the last few decades in combination with a genetic susceptibility (those with East Asian genes or with the genetics from myopic parents) have jointly contributed to the current myopia epidemic.305,313 Sorting out these competing hypotheses is a classic nature-versus-nurture challenge for the research community. 
If environmental changes are responsible for elevated levels of myopia, what characteristics of the environment are responsible? Experimental studies on animals support the hypothesis that the retina plays the central role in regulating eye growth (see accompanying IMI – Report on Experimental Models of Emmetropization and Myopia).314 Also, there is evidence that retina-specific environmental factors contribute to myopia development in humans, such as retinal light exposure of microscopists315 and retinal deprivation from ptosis/cataract.316 It is likely, therefore, that changes in the light environment (intensity, spectral content, optical distance) have contributed to this epidemic, rather than non-visual environmental factors such as air pollution and diet (see accompanying IMI – Interventions for Controlling Myopia Onset and Progression Report).317 
Establishing a causal relationship between environmental factors and myopia development is challenging for several reasons: 
  1.  
    The significant covariance of many factors potentially involved in myopia development, such as more time outside, will always be negatively correlated with less time inside.
  2.  
    Activities are generally different in indoor and outdoor environments. Sporting or other physical activities involving distant visual stimuli are common in the outdoor environment, whereas physically sedentary activities (such as watching TV and reading) combined with near viewing are common in interior environments. It is important to recognize that small differences in near viewing distances can dramatically alter the optical stimulus (target vergence), the accommodative response, and the defocus experienced by the eye.
  3.  
    Myopia development is slow (typically <1.0 D per year128,318), and refractive measures have coefficients of repeatability of about this magnitude, necessitating multi-year monitoring. On the other hand, measures of axial length have higher precision149 and can reliably detect smaller changes in myopia progression (such as those occurring over shorter periods of time).
  4.  
    Most studies assessing outdoor exposure time have employed survey tools. These questionnaires have ranged from a single question on outdoor activity319 to more detailed questionnaires estimating time engaged in a range of leisure and sporting outdoor activities on weekdays and weekends as utilized in the Sydney Myopia study320; however, accurate measures of the multidimensional properties of the visual environmental experienced by children are difficult to infer from these survey tools321 since they cannot quantify key parameters such as light level or viewing distance and are participant to recall bias.322 Studies have noted that there is generally poor agreement between outdoor exposure time derived from questionnaires and outdoor time derived from objective measures of outdoor light exposure.216,323
  5.  
    Standard corrections for myopia (such as single vision spectacle or contact lens corrections) may also alter retinal experience. This has also raised the question of whether traditional myopia treatments somehow contribute to the myopia progression of control groups in a clinical trial.324
  6.  
    Modern techniques have been able to quantify personal environmental light levels using wearable photodetectors216,325 and physical activity levels using accelerometers,325,326 providing the ability to give objective measures of outdoor exposure times in children. However, characteristics of the light environment determining the retinal image characteristics have not been specifically quantified. For example, because of the brow, the eye generally does not experience direct solar irradiation, whereas a light detector mounted on clothes can be directly illuminated by the sun. Will body-mounted light monitoring systems accurately reflect the true retinal illumination?
Some recent studies examining the relationship between myopia and outdoor activities have employed a range of different objective devices to estimate outdoor exposure, including wearable light sensors affixed to clothing (such as HOBO Pendant light loggers; Microdaq.com Ltd, USA)216,323,327 and wristwatch sensors that combine light sensors and measures of physical activity (such as Actiwatch devices; Philips Respironics, Andover, MA, USA)325,328,329 and the recently developed FitSight fitness tracker (Singapore Eye Research Institute, Singapore).215 These wearable sensors provide detailed objective assessments of light exposure patterns. Through continuous measures of light exposure, and current device battery life and data storage capacity, the devices can be worn for up to a month (recharging devices and the ability to wirelessly synchronize data to other smart devices should allow longer measurement periods). The majority of studies employing wearable light sensors to provide objective measures of outdoor exposure time have utilized a light intensity cutoff value of >1000 lux to delineate between outdoor and indoor exposure, since light levels >1000 lux are not commonly experienced when indoors.215,216,323,325,328 A recent study comparing light exposure measures (collected with a wristwatch light sensor) derived from a range of sampling frequencies and durations has recommended that for the most reliable measures of outdoor light exposure in children and adults, light exposure measures should be collected for at least a week with measurements sampled at least every 2 minutes.330 Recent technological advances also enable accurate monitoring of real-time viewing distances, to allow the dioptric mapping of the visual environment, which helps reveal any potential relationship between chronic viewing distances and myopia development.329,331333 
Finally, although the preponderance of evidence supports the idea that increased outdoor activities and, by necessity, decreased indoor time, are associated with lower levels of myopia,320,322 most of these studies can reveal only an association. A number of recent interventional studies have also shown that interventions to increase children's daily outdoor exposure time have resulted in significant reductions in myopia development compared to control groups.334336 Of course, there are some potentially confounding causal relationships (such as hyperopic children are less likely to read because of the increased accommodative demands and possible fusional failures that can result).337 Are these children more likely to spend time outside because of their refractive state and not vice versa? Further, because many outdoor activities require distance vision (such as playing cricket and baseball), children with myopia may be less inclined to participate in outdoor activities, again suggesting that it could be the refractive state causing the environmental differences and not the other way around. 
If myopia levels and progression are dominated by the refractive state at the start of a study, then environmental experiences prior to the emergence of myopia may be the causal agent,338 which is consistent with the key conclusion of Xiong and colleagues,322 that outdoor activity can protect against the onset of myopia but not its progression. These results suggest that environmental studies of children prior to the ages typically associated with myopia onset might be required to reveal environmental factors responsible for myopia onset. Another issue may be reliance on inaccurate measures of time spent outdoors,321 inadequate number of data samples,339 and body-mounted light dosimeters that might misrepresent the amount of light in the retinal image.340 
Because outdoor activities are often very different from those practiced indoors, activity becomes a significant covariable for environmental light levels. For example, in studies that did not directly measure physical activity,341 the significant association between emerging myopia and outdoor sports cannot be separated from the light exposure covariable. Studies that surveyed activities as well as time outside320 made tentative conclusions that it was more outdoor time and not sporting activities that were responsible for lower myopia rates in children. More recent studies that actually measured physical activity328,342 failed to find any association between physical activity and myopia development. 
Given the impact of light exposure and outdoor activities upon eye growth, there is potential for differences in outdoor exposure to interact with treatment effects in clinical myopia control trials. Clearly, the collection of detailed data to estimate outdoor time or light exposure in treatment and control populations is imperative for clinical myopia control trials involving interventions. In addition, during myopia clinical trials of optical devices or pharmacological agents, the season in which the study is commenced and measurements are collected should be at consistent times of the year for each child in a multi-year study. Nonetheless, measures at other time points throughout the year may be beneficial in supplementing annual measures since it is likely that enrollment in longitudinal clinical trials will stretch across multiple seasons. 
3.3.6 Anterior Segment Imaging
Scheimpflug imaging and Optical Coherence Tomography (OCT) have been extensively utilized to examine differences in the anterior chamber with refractive error, although they are not generally used to assess myopia control techniques. Longer axial length is associated with a flatter corneal curvature, decreased corneal thickness and decreased endothelial density.343346 Some studies have found that eyes with high myopia have thinner corneas than eyes with emmetropia or other refractive errors,347 whereas other studies showed no relationship between refractive error and corneal thickness.348 Anterior chamber depth has been found to be deeper in myopic eyes,346,347,349,350 creating an increase in anterior chamber volume.351353 
Several studies have reported the ciliary muscle, as imaged by OCT, to be thicker in myopic than in emmetropic eyes,354358 whereas others have not found a significant effect of a longer axial length on ciliary muscle thickness.359 Ciliary muscle thickness has been shown to be thicker temporally than nasally with an association with refractive error in humans.359 Ciliary muscle ring diameter increases (by 0.10 mm/D), the anterior lens surface steepens (by 0.011 mm/D),360 and crystalline lens depth from the anterior chamber decreases352 with increasing myopia. Changes in the anterior chamber depth with accommodation are significantly less pronounced in eyes with high myopia than in emmetropic eyes, but in some myopic eyes accommodation caused the anterior chamber to become critically shallow.361 
Studies utilizing Scheimpflug imaging have shown that OK lens wear alters the anterior corneal shape rather than the posterior corneal shape and the anterior chamber depth,362,363 although one study noted a slight flattening of the posterior corneal surface over 1 year.364 However, Chen et al.365 observed that steepening of the posterior cornea was observed immediately after lens removal, and it returned to its original shape within 2 hours after cessation of lens wear. Anterior segment biometric depths do not appear to change over either short-term (6 months)366 or long-term (2 years)367 OK, although axial length increases significantly. High resolution Scheimpflug imaging can calculate corneal power from its shape profile and, using this technique, has demonstrated that axial elongation over time is slower with greater OK-induced changes in refractive power between the central to the mid-peripheral cornea.368 
3.3.7 Posterior Segment Imaging
Since changes in posterior eye structures (such as the retina, choroid, and the optic nerve head) are known to accompany myopia,121,124,126,369371 imaging of posterior segment structures and the assessment of quantitative changes in posterior eye tissues are useful adjuncts to measures of refraction and axial length in myopia clinical trials. These measures provide insights into the mechanisms underlying observed refractive and eye length changes, and they contribute toward understanding the association between myopia and the development of posterior segment ocular pathology.372 While there is a variety of instruments available for the assessment of the posterior segment (such as ultrasound), the ability of Fourier-domain OCT to provide non-invasive, high-resolution posterior segment images allowing quantitative measures of both the retina (and individual retinal layers), choroid, and optic nerve, makes this an ideal technology for assessing posterior segment ocular structures in myopia research. 
Standard OCT imaging methods were designed to optimize retinal imaging; therefore, studies to quantify choroidal parameters should employ additional methods to optimize the image of the choroid and visibility of the chorio-scleral interface.373 Imaging techniques such as B-scan frame averaging and enhanced depth imaging are available on a number of commercial OCT devices for improving imaging of the choroid, and OCT's with longer wavelength light sources (for example, 1050 nm) also provide enhanced visibility of the choroid.374 A number of factors can influence the reliability of quantitative retinal, choroidal, and optic nerve measures from OCT images, such as the density of B-scans used to sample a retinal region, the registration of scan locations (within and between participants), magnification factors associated with differences in refractive error and axial length, refractive index assumptions, and between-participant variations in anatomical factors such as the disc-fovea angle.375,376 These potential confounding factors should be considered in clinical trials employing OCT imaging to draw the most reliable inferences from data. OCT image segmentation also often requires some manual checking by expert graders (particularly for choroidal measurements). Appropriate masking of image graders is required. 
Clinical trials assessing pharmacological or surgical-based myopia control interventions should also include posterior segment imaging to assess the potential for such treatments resulting in any adverse effects to the posterior segment (for example, retinal toxicity). While fundus photography and ophthalmoscopy are typically employed in clinical trials to assess adverse retinal effects associated with pharmacological treatments, additional retinal measures—such as fundus autofluorescence, OCT imaging, and electroretinogram techniques—provide additional structural and functional retinal measures that are useful in the assessment of possible retinal toxicity.377,378 
3.3.7.1 Retinal Contour Determination
Methods for assessing ocular biometry and imaging the posterior segment can also be used to derive measures of retinal shape.379 Retinal shape is an important factor influencing peripheral refraction.373 Retinal shape has been considered for emmetropic versus myopic eyes, in different races, and for retinal asymmetry. In the future, it could be used to monitor the effects of treatments as something more sophisticated than determining changes in axial length. Retinal shape has been determined by several methods, including X-ray radiography, ultrasonography, computerized X-ray tomography, partial coherence tomography, OCT, and magnetic resonance imaging (MRI).380 
A direct way of determining retinal shape is with the use of MRI, which is not affected by imaging through the eye but has low resolution on the order of 0.25 mm in-plane.381 A number of factors determine resolution, including the types and configuration of the radio-frequency coils used to transmit and receive the radio-frequency pulses, the imaging pulse sequences employed, and whether 2-dimensional or 3-dimensional data are required. Fine features such as the foveal pit cannot be resolved, meaning that estimations have to be made of the visual axis. It is somewhat impractical for clinical trials due to its testing time, current poor availability, and high expense. 
Because of optical distortions, methods such as partial coherence tomography and OCT must be combined with other biometric measurements and with ray tracing based on optical eye models. These methods seem promising in approximating measures of retinal shape obtained from MRI.379,382 While MRI can yield good eye shape estimates for the majority of retinas, it is probably not that helpful for restricted regions of the retina corresponding to the ±30° field in which peripheral refraction measurements are usually made383; the other methods may be of more value for such restricted regions. 
Different estimates of retinal shape have been made. These include ratios of axial length to the horizontal and vertical dimensions (the latter two usually measured from one side of the retina to the other),106 ellipse or ellipsoidal dimensions giving estimates of surface asphericity,383,384 type of retinal stretching in myopia (such as global, equatorial, posterior polar, and axial),380 retinal asymmetry such as comparing retinal distances to a nodal point in different meridians,381 and inferences of the overall eye shape as being oblate or prolate on the basis of an eye having relative peripheral myopia or relative peripheral hyperopia, respectively. 
3.3.8 Tissue Biomechanics
3.3.8.1 Sclera
Scleral biomechanical changes are known to occur with increasing levels of myopia in the human eye.385387 Specifically, axial elongation has been found to be associated with weakened biomechanical properties of the posterior sclera.388 It is unclear whether these biomechanical changes are a precursor to or a consequence of myopia. It is proposed that an accurate non-invasive assessment of material properties of the sclera in vivo would enable early detection and monitoring of eyes at risk of developing myopia as well as improving our understanding of the mechanism by which these alterations occur. 
Non-invasive strategies with potential clinical applications have included: MRI imaging,389 anterior OCT,390 indentation tonometry,391 ocular and fundus pulse amplitudes,392 ultrasound elastography,393 assessment of axial length changes following manipulation of external pressure,394 and internal IOP.395 Despite such attempts, most of these methodologies are crude and lack the accuracy and sensitivity needed to identify changes in tissues strength between myopic and non-myopic eyes.396 
With the growing popularity of corneal collagen cross-linking (CXL) for treating keratoconus, there is interest in the application of CXL to the sclera to possibly arrest axial growth.397 Thus far, scleral CXL has been assessed only in animal models, with early results showing increased biomechanical strength and reduced rate of myopic changes.398,399 At present, if CXL is applied to the in vivo human sclera due to technical limitations in assessing scleral biomechanics, outcome measures are likely to be limited to biometry and refractive error changes. 
3.3.8.2 Cornea
Given that the biomechanical assessment of the in vivo sclera is limited, much of the research relating to myopia and ocular biomechanics concerns the cornea. As both structures are predominantly composed of collagen and have similar embryological origins, it is generally assumed that scleral biomechanical changes may translate into corneal alterations.400 The validity of this assumption is unclear and there is significant ambiguity in the literature as to whether corneal structural and biomechanical changes occur in myopia.401403 Nonetheless, it is widely agreed that corneal biomechanics is important in OK and considered to be a significant outcome measure.404,405 Indeed, improved understanding of how biomechanics of the anterior ocular surface vary during myopic OK will provide a better understanding of the role of tissue biomechanics in the corneal shape change induced during treatment. Biomechanics can also inform improved lens design for individual patients. Basic structural attributes of the cornea are commonly assessed by pachymetry and topography,406408 while techniques such as the corneal deformation to air pressure response provide the means to assess dynamic corneal biomechanics in vivo.403,405,409,410 
4. Conclusions
This report presents recommendations from International Myopia Institute members on clinical trial protocols and instrumentation to assess the efficacy of myopia control treatments. A general consensus on study design was reached regarding: 
  •  
    The clinical trial protocol should adhere to the tenets of the Declaration of Helsinki and be approved by the appropriate local ethics committee. Informed consent should be written in a simple language and be acquired from both guardians and children. An adverse event reporting standard should be established. Clinical trials should be registered on a recognized clinical trials registry.
  •  
    Minimum length of a clinical trial is 3 years, with year 3 being without treatment (or with only control treatment) to assess any rebound effect.
  •  
    Participant inclusion and exclusion criteria should be clearly defined to include age, spherical equivalent refractive error, astigmatism, anisometropia, and ocular pathology. Participants with a history of any previous myopia control treatment should be excluded.
  •  
    The included participants should be randomized into one (or several) treatment group(s) and one control group. Stratified randomization is useful to achieve age-matched and level of refractive error-matched groups.
  •  
    The control group should receive a treatment that, as far as possible, cannot be distinguished from the active treatment, including the information provided and the ocular health assessment conducted. Common control treatments are single vision spectacles, monofocal soft contact lenses, and a similar vehicle for pharmacological interventions.
  •  
    The examiner collecting outcome data should always be masked to the group-belonging of the participant. Masking of the participant should be utilized whenever possible.
The International Myopia Institute strongly recommends using axial length as primary outcome measure of the efficacy of myopia control treatments as well as refractive error when applicable. Axial length should be assessed with an optical biometric method, such as optical partial coherence interferometry that provides non-contact measurements with high accuracy and precision. Refractive errors should be measured objectively under cycloplegia with an open-field autorefractor with a known measurement aperture that can be repeatedly located close to the pupil center. The same type of cycloplegic agent (preferably 1% tropicamide with optical treatments) should be used throughout the clinical trial, and refraction must not be measured before the maximal cycloplegic effect has been achieved (an assessment of depth of cycloplegia should be made before measurement). The refractive errors should be expressed as mean spherical equivalent and astigmatic power errors. To ensure accuracy, the same instrumentation should be used throughout the time period of the clinical trial and must be calibrated and validated using an eye-model. The procedure should be carefully described to allow for easy comparison, replication, and benchmarking. Finally, when stating the reduction in axial elongation and myopia progression between a treatment and a control group, it is critical to report the time period over which the reduction occurred. The meaningful treatment effect over 3 years (2 years treatment + 1 year of no treatment to identify any rebound effect) should be considered on a study-by-study basis on factors identified in section 2.9 (see Fig. 1). 
This report also provides an overview of secondary and exploratory outcomes, which could be useful for future instrumentation and treatment development (Table 5): 
  •  
    Treatment and visit compliance is important for the validity of the conclusion of a clinical trial. Electronic reporting and reminders (e.g., via text messages) have been shown to increase compliance.
  •  
    Participantive reporting on comfort and visual quality during treatment is often assessed via questionnaires, preferably electronic. Furthermore, for any participants who discontinue treatment, the reason for discontinuation should be documented.
  •  
    Binocular vision, heterophoria, and accommodative function (at a minimum lag of accommodation and consider accommodation facility) correlate with the efficiency of the myopia control treatment and should at least be assessed at baseline of the clinical trial.
  •  
    Several different modalities to measure visual function exist. Participantive visual acuity should be determined with logMAR charts. Additionally, contrast sensitivity, reading speed, and glare estimation can provide more detailed knowledge because they are more sensitive to the quality of the retinal image.
  •  
    Peripheral refraction may be associated with myopia progression and should be measured using a method such as an open-field autorefractor validated for the purpose. Preferably, head-turn should be used instead of eye-turn. The most susceptible retinal area is not known, but as a starting point it is recommended to assess the optical errors 30° in the temporal visual field and also the corresponding angle in the nasal visual field. Further out in the periphery, measures of retinal shape may also provide estimates of the peripheral refractive errors.
  •  
    Outdoor versus indoor activity is also associated with myopia; outdoor activity early in life possibly protects against onset of myopia, but with equivocal evidence for progression. Environmental studies of children prior to the ages typically associated with myopia onset might be required, with new technologies to enable more complete descriptions of the child's visual environment. Furthermore, differences in outdoor exposure may interact with treatment effects, and the protocol of clinical myopia control trials should be designed to account for the influence of seasonal variation on the estimated yearly progression of myopia.
  •  
    Give detailed assessments of the ocular biometry; for instance, OCT is of special importance for some myopia treatments. Pharmacological- or surgical-based myopia control interventions should include posterior segment imaging to assess any adverse effects to the posterior segment. In OK, information on the anterior segment, especially corneal curvature and thickness, is essential, but corneal tissue biomechanics is also important to improve the lens design. Lens position and thickness may also vary prior to and during myopia progression, and an assessment of these at baseline and study end is warranted.
Table 5
 
Expected Minimum Data Set for Each Treatment Modality
Table 5
 
Expected Minimum Data Set for Each Treatment Modality
Acknowledgments
The authors thank David S. Friedman, MD, Dana Center for Preventive Ophthalmology Wilmer Eye Institute and Bloomberg School of Public Health Senior Ophthalmologist, for his review of the manuscript. 
Supported by the International Myopia Institute. Publication costs of the International Myopia Institute reports were supported by donations from the Brien Holden Vision Institute, Carl Zeiss Vision, Coopervision, Essilor, Alcon, and Vision Impact Institute. 
Disclosure: J.S. Wolffsohn, Alcon (F), Allergan (F), Aston EyeTech (F, I), Atiya Vision (C), Bausch & Lomb (F), BetterVision Ltd (F), British Contact Lens Association (C), CooperVision (F, C), Eaglet Eye (F), European Union (F), Eyebag (F), EMPharma (F), EyeDocs (F), Gelflex (F), Innovate UK (F), Johnson & Johnson Vision Care (F, C, R), Lenstec (F), Medmont (F), Rayner (F), Santen (C, R), Shire (C), Tearlab (F), Théa (F), Optimec (F), University of Houston (C), Visioncare Research (F, C), P; P.S. Kollbaum, Alcon (F), Allergan (F), CooperVision (F, C, R), Johnson & Johnson Vision Care (F, R), Luminopia (F), P; D.A. Bernsten, Bausch & Lomb (F), Visioneering Technologies (C); D.A. Atchison, Carl Zeiss Vision (F), Cylite Optics (F), ForgetSpecs (F), P; A. Benavente, None; A. Bradley, CooperVision (F, C), Alcon (F, C), Vistakon (F, C), Allergan (F, C); H. Buckhurst, None; M. Collins, Johnson & Johnson Vision Care (F, C, R), Cylite (F), Johnson & Johnson Vision (F), P; T. Fujikado, Nidek (F), Topcon (F), Menicon (F), Hoya (F), P; T. Hiraoka, Johnson & Johnson Vision Care (F), Seed (F), Alpha Corporation (F), Menicon (R), Santen (R); M. Hirota, None; D. Jones, Coopervision (C), Shire (C), Alcon (C); N.S. Logan, CooperVision (F), Visioncare Research (F); L. Lundström, Abbott (F), Alcon (C), P; H. Torii, P; S.A. Read, Cylite Pty Ltd., (F), P; K. Naidoo, None 
References
Comet G. Myopia stabilization and associated factors among participants in the Correction of Myopia Evaluation Trial (COMET). Invest Ophthalmol Vis Sci. 2013; 54: 7871–7884.
Chua SY, Sabanayagam C, Cheung YB, et al. Age of onset of myopia predicts risk of high myopia in later childhood in myopic Singapore children. Ophthalmic Physiol Opt. 2016; 36: 388–394.
Goss DA, Winkler RL. Progression of myopia in youth: age of cessation. Am J Optom Physiol Opt. 1983; 60: 651–658.
Donovan L, Sankaridurg P, Ho A, Naduvilath T, Smith ELIII, Holden BA. Myopia progression rates in urban children wearing single-vision spectacles. Optom Vis Sci. 2012; 89: 27–32.
Morgan IG, French AN, Ashby RS, et al. The epidemics of myopia: aetiology and prevention. Prog Retin Eye Res. 2018; 62: 134–149.
Chamberlain P, Back A, Lazon de la Jara P, et al. Effectiveness of a dual-focus 1 day soft contact lens for myopia control. Presented at: the British Contact Lens Association Clinical Conference. Liverpool, United Kingdom; 2017.
Gwiazda J, Hyman L, Hussein M, et al. A randomized clinical trial of progressive addition lenses versus single vision lenses on the progression of myopia in children. Invest Ophthalmol Vis Sci. 2003; 44: 1492–1500.
Fulk GW, Cyert LA, Parker DE. A randomized clinical trial of bifocal glasses for myopic children with esophoria: results after 54 months. Optometry. 2002; 73: 470–476.
Correction of Myopia Evaluation Trial 2 Study Group for the Pediatric Eye Disease Investigator Group. Progressive-addition lenses versus single-vision lenses for slowing progression of myopia in children with high accommodative lag and near esophoria. Invest Ophthalmol Vis Sci. 2011; 52: 2749–2757.
Hiraoka T, Kakita T, Okamoto F, Takahashi H, Oshika T. Long-term effect of overnight orthokeratology on axial length elongation in childhood myopia: a 5-year follow-up study. Invest Ophthalmol Vis Sci. 2012; 53: 3913–3919.
Edwards MH, Li RW, Lam CS, Lew JK, Yu BS. The Hong Kong progressive lens myopia control study: study design and main findings. Invest Ophthalmol Vis Sci. 2002; 43: 2852–2858.
Gwiazda J, Marsh-Tootle WL, Hyman L, Hussein M, Norton TT, Group CS. Baseline refractive and ocular component measures of children enrolled in the correction of myopia evaluation trial (COMET). Invest Ophthalmol Vis Sci. 2002; 43: 314–321.
Hasebe S, Ohtsuki H, Nonaka T, et al. Effect of progressive addition lenses on myopia progression in Japanese children: a prospective, randomized, double-masked, crossover trial. Invest Ophthalmol Vis Sci. 2008; 49: 2781–2789.
Hasebe S, Jun J, Varnas SR. Myopia control with positively aspherized progressive addition lenses: a 2-year, multicenter, randomized, controlled trial. Invest Ophthalmol Vis Sci. 2014; 55: 7177–7188.
Adler D, Millodot M. The possible effect of undercorrection on myopic progression in children. Clin Exp Optom. 2006; 89: 315–321.
Sun YY, Li SM, Li SY, et al. Effect of uncorrection versus full correction on myopia progression in 12-year-old children. Graefes Arch Clin Exp Ophthalmol. 2017; 255: 189–195.
Walline JJ, Jones LA, Sinnott LT. Corneal reshaping and myopia progression. Br J Ophthalmol. 2009; 93: 1181–1185.
Kakita T, Hiraoka T, Oshika T. Influence of overnight orthokeratology on axial elongation in childhood myopia. Invest Ophthalmol Vis Sci. 2011; 52: 2170–2174.
Cho P, Cheung SW. Retardation of Myopia in Orthokeratology (ROMIO) study: a 2-year randomized clinical trial. Invest Ophthalmol Vis Sci. 2012; 53: 7077–7085.
Santodomingo-Rubido J, Villa-Collar C, Gilmartin B, Gutierrez-Ortega R. Myopia control with orthokeratology contact lenses in Spain: refractive and biometric changes. Invest Ophthalmol Vis Sci. 2012; 53: 5060–5065.
Aller TA, Liu M, Wildsoet CF. Myopia control with bifocal contact lenses: a randomized clinical trial. Optom Vis Sci. 2016; 93: 344–352.
Lam CS, Tang WC, Tse DY, Tang YY, To CH. Defocus Incorporated Soft Contact (DISC) lens slows myopia progression in Hong Kong Chinese schoolchildren: a 2-year randomised clinical trial. Br J Ophthalmol. 2014; 98: 40–45.
Pomeda AR, Perez-Sanchez B, Canadas Suarez MDP, Prieto Garrido FL, Gutierrez-Ortega R, Villa-Collar C. MiSight Assessment Study Spain: a comparison of vision-related quality-of-life measures between MiSight contact lenses and single-vision spectacles. Eye Contact Lens. 2018; 44: S99–S104.
Walline JJ, Greiner KL, McVey ME, Jones-Jordan LA. Multifocal contact lens myopia control. Optom Vis Sci. 2013; 90: 1207–1214.
Fujikado T, Ninomiya S, Kobayashi T, Suzaki A, Nakada M, Nishida K. Effect of low-addition soft contact lenses with decentered optical design on myopia progression in children: a pilot study. Clin Ophthalmol. 2014; 8: 1947–1956.
Paune J, Morales H, Armengol J, Quevedo L, Faria-Ribeiro M, Gonzalez-Meijome JM. Myopia control with a novel peripheral gradient soft lens and orthokeratology: a 2-year clinical trial. Biomed Res Int. 2015; 2015: 507572.
Cheng X, Xu J, Chehab K, Exford J, Brennan N. Soft contact lenses with positive spherical aberration for myopia control. Optom Vis Sci. 2016; 93: 353–366.
Walline JJ, Gaume Giannoni A, Sinnott LT, et al. A randomized trial of soft multifocal contact lenses for myopia control: baseline data and methods. Optom Vis Sci. 2017; 94: 856–866.
Chua WH, Balakrishnan V, Chan YH, et al. Atropine for the treatment of childhood myopia. Ophthalmology. 2006; 113: 2285–2291.
Chia A, Chua WH, Cheung YB, et al. 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. 2012; 119: 347–354.
Polling JR, Kok RG, Tideman JW, Meskat B, Klaver CC. Effectiveness study of atropine for progressive myopia in Europeans. Eye (Lond). 2016; 30: 998–1004.
Wang YR, Bian HL, Wang Q. Atropine 0.5% eyedrops for the treatment of children with low myopia: a randomized controlled trial. Medicine (Baltimore). 2017; 96: e7371.
Cheng D, Schmid KL, Woo GC, Drobe B. Randomized trial of effect of bifocal and prismatic bifocal spectacles on myopic progression: two-year results. Arch Ophthalmol. 2010; 128: 12–19.
Berntsen DA, Sinnott LT, Mutti DO, Zadnik K. A randomized trial using progressive addition lenses to evaluate theories of myopia progression in children with a high lag of accommodation. Invest Ophthalmol Vis Sci. 2012; 53: 640–649.
Hulley SB, Cummings SR, Browner WS, Grady DG, Newman TB. Designing Clinical Research. 3rd ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2007.
Jones-Jordan LA, Hoppe ES. Putting Research into Clinical Practice. New York: Old Post Publishing; 2009.
Lin Z, Martinez A, Chen X, et al. Peripheral defocus with single-vision spectacle lenses in myopic children. Optom Vis Sci. 2010; 87: 4–9.
Moore KE, Benoit JS, Berntsen DA. Spherical soft contact lens designs and peripheral defocus in myopic eyes. Optom Vis Sci. 2017; 94: 370–379.
Tabernero J, Vazquez D, Seidemann A, Uttenweiler D, Schaeffel F. Effects of myopic spectacle correction and radial refractive gradient spectacles on peripheral refraction. Vision Res. 2009; 49: 2176–2186.
Kang P, Fan Y, Oh K, Trac K, Zhang F, Swarbrick H. Effect of single vision soft contact lenses on peripheral refraction. Optom Vis Sci. 2012; 89: 1014–1021.
Kwok E, Patel B, Backhouse S, Phillips JR. Peripheral refraction in high myopia with spherical soft contact lenses. Optom Vis Sci. 2012; 89: 263–270.
Walline JJ, Jones LA, Sinnott L, et al. A randomized trial of the effect of soft contact lenses on myopia progression in children. Invest Ophthalmol Vis Sci. 2008; 49: 4702–4706.
Horner DG, Soni PS, Salmon TO, Swartz TS. Myopia progression in adolescent wearers of soft contact lenses and spectacles. Optom Vis Sci. 1999; 76: 474–479.
Walline JJ, Jones LA, Mutti DO, Zadnik K. A randomized trial of the effects of rigid contact lenses on myopia progression. Arch Ophthalmol. 2004; 122: 1760–1766.
Manny RE, Hussein M, Scheiman M, Kurtz D, Niemann K, Zinzer K. Tropicamide (1%): an effective cycloplegic agent for myopic children. Invest Ophthalmol Vis Sci. 2001; 42: 1728–1735.
Egashira SM, Kish LL, Twelker JD, Mutti DO, Zadnik K, Adams AJ. Comparison of cyclopentolate versus tropicamide cycloplegia in children. Optom Vis Sci. 1993; 70: 1019–1026.
Chia A, Lu QS, Tan D. Five-year clinical trial on atropine for the treatment of myopia 2: myopia control with atropine 0.01% eyedrops. Ophthalmology. 2016; 123: 391–399.
Gwiazda J, Deng L, Manny R, Norton TT; COMET Study Group. Seasonal variations in the progression of myopia in children enrolled in the correction of myopia evaluation trial. Invest Ophthalmol Vis Sci. 2014; 55: 752–758.
Edwards IR, Biriell C. Harmonisation in pharmacovigilance. Drug Saf. 1994; 10: 93–102.
U.S. Food and Drug Administration. Guideline for Industry: Clinical Safety Data Management: Definitions and Standards for Expedited Reporting (1995). Available at: https://www.fda.gov/downloads/drugs/guidances/ucm073087.pdf. Accessed February 7, 2019.
Stark NJ. A new standard for medical device adverse event classification. J Clin Res Best Pract. 2009; 5. Available at: http://firstclinical.com/journal/2009/0912_ISO_14155.pdf. Accessed February 7, 2019.
Begley CG, Caffery B, Nichols KK, Chalmers R. Responses of contact lens wearers to a dry eye survey. Optom Vis Sci. 2000; 77: 40–46.
Holden BA, Sweeney DF, Vannas A, Nilsson KT, Efron N. Effects of long-term extended contact lens wear on the human cornea. Invest Ophthalmol Vis Sci. 1985; 26: 1489–1501.
Holden BA, Vannas A, Nilsson K, et al. Epithelial and endothelial effects from the extended wear of contact lenses. Curr Eye Res. 1985; 4: 739–742.
Liesegang TJ. Physiologic changes of the cornea with contact lens wear. CLAO J. 2002; 28: 12–27.
U.S. Food and Drug Administration. MedWatch Online Voluntary Reporting Form. Available at: https://www.fda.gov/Safety/MedWatch/HowToReport/DownloadForms/default.htm. Accessed February 7, 2019.
Chalmers RL, Keay L, Long B, Bergenske P, Giles T, Bullimore MA. Risk factors for contact lens complications in US clinical practices. Optom Vis Sci. 2010; 87: 725–735.
Bullimore MA. The safety of soft contact lenses in children. Optom Vis Sci. 2017; 94: 638–646.
Saw SM, Gazzard G, Au Eong KG, Tan DT. Myopia: attempts to arrest progression. Br J Ophthalmol. 2002; 86: 1306–1311.
Tan DT, Lam DS, Chua WH, Shu-Ping DF, Crockett RS; Asian Pirenzepine Study Group. One-year multicenter, double-masked, placebo-controlled, parallel safety and efficacy study of 2% pirenzepine ophthalmic gel in children with myopia. Ophthalmology. 2005; 112: 84–91.
Bartlett JD, Niemann K, Houde B, Allred T, Edmondson MJ, Crockett RS. A tolerability study of pirenzepine ophthalmic gel in myopic children. J Ocul Pharmacol Ther. 2003; 19: 271–279.
Assmann SF, Pocock SJ, Enos LE, Kasten LE. Subgroup analysis and other (mis)uses of baseline data in clinical trials. Lancet. 2000; 355: 1064–1069.
Pollack AL, Brodie SE. Diagnostic yield of the routine dilated fundus examination. Ophthalmology. 1998; 105: 382–386.
Jones D, Luensmann D. The prevalence and impact of high myopia. Eye Contact Lens. 2012; 38: 188–196.
Iwase A, Araie M, Tomidokoro A, et al. Prevalence and causes of low vision and blindness in a Japanese adult population: the Tajimi Study. Ophthalmology. 2006; 113: 1354–1362.
Xu L, Wang Y, Li Y, et al. Causes of blindness and visual impairment in urban and rural areas in Beijing: the Beijing Eye Study. Ophthalmology. 2006; 113: 1134.
Oku Y, Oku H, Park M, et al. Long axial length as risk factor for normal tension glaucoma. Graefes Arch Clin Exp Ophthalmol. 2009; 247: 781–787.
Vongphanit J, Mitchell P, Wang JJ. Prevalence and progression of myopic retinopathy in an older population. Ophthalmology. 2002; 109: 704–711.
Ogawa A, Tanaka M. The relationship between refractive errors and retinal detachment –analysis of 1,166 retinal detachment cases. Jpn J Ophthalmol. 1988; 32: 310–315.
Flitcroft DI. The complex interactions of retinal, optical and environmental factors in myopia aetiology. Prog Retin Eye Res. 2012; 31: 622–660.
Parisi ML, Scheiman M, Coulter RS. Comparison of the effectiveness of a nondilated versus dilated fundus examination in the pediatric population. J Am Optom Assoc. 1996; 67: 266–272.
Walling P, Pole J, Karpecki P, Colatrella N, Varanelli J. Condensing Lenses: Sharpen Your Skills in Choosing and Using. Available at: https://www.reviewofoptometry.com/article/condensing-lenses-sharpen-your-skills-in-choosing-and-using. Accessed February 7, 2019.
Quinn T. Slit Lamp Examination: Back to Basics. Available at: https://www.clspectrum.com/supplements/2006/february-2006/protecting-your-patient-s-eye-health/contact-lens-practive-pearls. Accessed February 7, 2019.
Gaston DC. The slit lamp biomicroscope in the contact lens examination. J Ophthalmic Nurs Technol. 1984; 3: 82–85.
Wolffsohn JS, Naroo SA, Christie C, et al. Anterior eye health recording. Cont Lens Anterior Eye. 2015; 38: 266–271.
Bodack MI, Chung I, Krumholtz I. An analysis of vision screening data from New York City public schools. Optometry. 2010; 81: 476–484.
Junghans B, Kiely PM, Crewther DP, Crewther SG. Referral rates for a functional vision screening among a large cosmopolitan sample of Australian children. Ophthalmic Physiol Opt. 2002; 22: 10–25.
Owsley C, Sloane ME. Contrast sensitivity, acuity, and the perception of ‘real-world'' targets. Br J Ophthalmol. 1987; 71: 791–796.
Gong CR, Troilo D, Richdale K. Accommodation and phoria in children wearing multifocal contact lenses. Optom Vis Sci. 2017; 94: 353–360.
Anstice NS, Phillips JR. Effect of dual-focus soft contact lens wear on axial myopia progression in children. Ophthalmology. 2011; 118: 1152–1161.
Kang P, Wildsoet CF. Acute and short-term changes in visual function with multifocal soft contact lens wear in young adults. Cont Lens Anterior Eye. 2016; 39: 133–140.
Loughman J, Flitcroft DI. The acceptability and visual impact of 0.01% atropine in a Caucasian population. Br J Ophthalmol. 2016; 100: 1525–1529.
Yu X, Zhang B, Bao J, et al. Design, methodology, and baseline data of the Personalized Addition Lenses Clinical Trial (PACT). Medicine (Baltimore). 2017; 96: e6069.
Bailey IL. Perspective: visual acuity – keeping it clear. Optom Vis Sci. 2012; 89: 1247–1248.
Li SM, Liu LR, Li SY, et al. Design, methodology and baseline data of a school-based cohort study in Central China: the Anyang Childhood Eye Study. Ophthalmic Epidemiol. 2013; 20: 348–359.
Zhao HL, Jiang J, Yu J, Xu HM. Role of short-wavelength filtering lenses in delaying myopia progression and amelioration of asthenopia in juveniles. Int J Ophthalmol. 2017; 10: 1261–1267.
Flitcroft DI, He M, Jonas JB, et al. IMI – Defining and classifying myopia: a proposed set of standards for clinical and epidemiologic studies. Invest Ophthalmol Vis Sci. 2019; 60: M20–M30.
Heyse JF. Outcome measures in clinical trials. In: Wiley StatsRef: Statistics Reference Online. John Wiley and Sons, Ltd; 2014.
Coster WJ. Making the best match: selecting outcome measures for clinical trials and outcome studies. Am J Occup Ther. 2013; 67: 162–170.
Cho P, Cheung SW, Edwards MH. The longitudinal orthokeratology research in children (LORIC) in Hong Kong: a pilot study on refractive changes and myopic control. Curr Eye Res. 2005; 30: 71–80.
Cho P, Cheung SW. Discontinuation of orthokeratology on eyeball elongation (DOEE). Cont Lens Anterior Eye. 2017; 40: 82–87.
Cho P, Cheung SW. Protective role of orthokeratology in reducing risk of rapid axial elongation: a reanalysis of data from the ROMIO and TO-SEE Studies. Invest Ophthalmol Vis Sci. 2017; 58: 1411–1416.
Shih YF, Chen CH, Chou AC, Ho TC, Lin LLK, Hung PT. Effects of different concentrations of atropine on controlling myopia in myopic children. J Ocul Pharmacol Ther. 1999; 15: 85–90.
Sankaridurg P, Holden B, Smith EIII, et al. Decrease in rate of myopia progression with a contact lens designed to reduce relative peripheral hyperopia: one-year results. Invest Ophthalmol Vis Sci. 2011; 52: 9362–9367.
Chung K, Mohidin N, O'Leary DJ. Undercorrection of myopia enhances rather than inhibits myopia progression. Vision Res. 2002; 42: 2555–2559.
Fulk GW, Cyert LA, Parker DE. A randomized trial of the effect of single-vision vs. bifocal lenses on myopia progression in children with esophoria. Optom Vis Sci. 2000; 77: 395–401.
Yang Z, Lan W, Ge J, et al. The effectiveness of progressive addition lenses on the progression of myopia in Chinese children. Ophthalmic and Physiological Optics. 2009; 29: 41–48.
Walline JJ, Rah M, Jones LA. The children's overnight orthokeratology investigation (COOKI) pilot study. Optom Vis Sci. 2004; 81: 407–413.
Goss DA. Effect of bifocal lenses on the rate of childhood myopia progression. Am J Optom Physiol Opt. 1986; 63: 135–141.
Oakley KH, Young FA. Bifocal control of myopia. Am J Optom Physiol Opt. 1975; 52: 758–764.
Santodomingo-Rubido J, Mallen EA, Gilmartin B, Wolffsohn JS. A new non-contact optical device for ocular biometry. Br J Ophthalmol. 2002; 86: 458–462.
Buckhurst PJ, Wolffsohn JS, Shah S, Naroo SA, Davies LN, Berrow EJ. A new optical low coherence reflectometry device for ocular biometry in cataract patients. Br J Ophthalmol. 2009; 93: 949–953.
Bullimore MA, Fusaro RE, Adams CW. The repeatability of automated and clinician refraction. Optom Vis Sci. 1998; 75: 617–622.
Walline JJ, Lindsley K, Vedula SS, Cotter SA, Mutti DO, Twelker JD. Interventions to slow progression of myopia in children. Cochrane Database Syst Rev. 2011; 12: CD004916.
Olsen T, Arnarsson A, Sasaki H, Sasaki K, Jonasson F. On the ocular refractive components: the Reykjavik Eye Study. Acta Ophthalmol Scand. 2007; 85: 361–366.
Atchison DA, Jones CE, Schmid KL, et al. Eye shape in emmetropia and myopia. Invest Ophthalmol Vis Sci. 2004; 45: 3380–3386.
Stenstrom S. Investigation of the variation and the correlation of the optical elements of human eyes. Am J Optom Arch Am Acad Optom. 1948; 25: 496–504.
Richter GM, Wang M, Jiang X, et al. Ocular determinants of refractive error and its age- and sex-related variations in the Chinese American eye study. JAMA Ophthalmol. 2017; 135: 724–732.
Curtin BJ, Karlin DB. Axial length measurements and fundus changes of the myopic eye. Am J Ophthalmol. 1971; 71: 42–53.
Jonas JB, Ohno-Matsui K, Spaide RF, Holbach L, Panda-Jonas S. Macular Bruch's membrane defects and axial length: association with gamma zone and delta zone in peripapillary region. Invest Ophthalmol Vis Sci. 2013; 54: 1295–1302.
Jonas JB, Xu L. Histological changes of high axial myopia. Eye. 2014; 28: 113–117.
Wiesel TN, Raviola E. Myopia and eye enlargement after neonatal lid fusion in monkeys. Nature. 1977; 266: 66–68.
Schaeffel F, Glasser A, Howland HC. Accommodation, refractive error and eye growth in chickens. Vision Res. 1988; 28: 639–657.
Wallman J, Adams JI. Developmental aspects of experimental myopia in chicks. Vision Res. 1987; 27: 1139–1163.
Irving EL, Sivak JG, Callender MG. Refractive plasticity of the developing chick eye. Ophthalmic Physiol Opt. 1992; 12: 448–456.
Troilo D, Judge S. Ocular development and visual deprivation myopia in the common marmoset (Callithrix jacchus). Vision Res. 1993; 33: 1311–1324.
Smith ELIII. Environmentally induced refractive errors in animals. In: Rosenfield M, Gilmartin B, eds. Myopia and Nearwork. Oxford: Butterworth Heinemann; 1998: 57–90.
Kröger RHH, Wagner HJ. The eye of the blue acara (Aequidens pulcher, Cichlidae) grows to compensate for defocus due to chromatic aberration. J Comp Physiol A Neuroethol Sens Neural Behav Physiol. 1996; 179: 837–842.
Shaikh AW, Siegwart JT, Norton TT. Effect of interrupted lens wear on compensation for minus lens in tree shrews. Optom Vis Sci. 1999; 76: 308–315.
McFadden SA, Howlett MH, Mertz JR. Retinoic acid signals the direction of ocular elongation in the guinea pig eye. Vision Res. 2004; 44: 643–653.
Ikuno Y, Tano Y. Retinal and choroidal biometry in highly myopic eyes with spectral-domain optical coherence tomography. Invest Ophthalmol Vis Sci. 2009; 50: 3876–3880.
Li L-J, Cheung CY-L, Gazzard G, et al. Relationship of ocular biometry and retinal vascular caliber in preschoolers. Invest Ophthalmol Vis Sci. 2011; 52: 9561–9566.
Li M, Yang Y, Jiang H, et al. Retinal microvascular network and microcirculation assessments in high myopia. Am J Ophthalmol. 2017; 174: 56–67.
Read SA, Collins MJ, Vincent SJ, Alonso-Caneiro D. Choroidal thickness in myopic and nonmyopic children assessed with enhanced depth imaging optical coherence tomography. Invest Ophthalmol Vis Sci. 2013; 54: 7578–7586.
Maruko I, Iida T, Sugano Y, Oyamada H, Akiba M, Sekiryu T. Morphologic analysis in pathologic myopia using high-penetration optical coherence tomography. Invest Ophthalmol Vis Sci. 2012; 53: 3834–3838.
Read SA, Alonso-Caneiro D, Vincent SJ. Longitudinal changes in macular retinal layer thickness in pediatric populations: myopic vs, non-myopic eyes. PLoS One. 2017; 12: e0180462.
Pierro L, Camesasca FI, Mischi M, Brancato R. Peripheral retinal changes and axial myopia. Retina. 1992; 12: 12–17.
Saw SM, Chua WH, Gazzard G, Koh D, Tan DT, Stone RA. Eye growth changes in myopic children in Singapore. Br J Ophthalmol. 2005; 89: 1489–1494.
Stone RA, Quinn GE, Francis EL, et al. Diurnal axial length fluctuations in human eyes. Invest Ophthalmol Vis Sci. 2004; 45: 63–70.
Read SA, Collins MJ, Iskander DR. Diurnal variation of axial length, intraocular pressure, and anterior eye biometrics. Invest Ophthalmol Vis Sci. 2008; 49: 2911–2918.
Drexler W, Findl O, Schmetterer L, Hitzenberger CK, Fercher AF. Eye elongation during accommodation in humans: differences between emmetropes and myopes. Invest Ophthalmol Vis Sci. 1998; 39: 2140–2147.
Read SA, Collins MJ, Woodman EC, Cheong SH. Axial length changes during accommodation in myopes and emmetropes. Optom Vis Sci. 2010; 87: 656–662.
Leydolt C, Findl O, Drexler W. Effects of change in intraocular pressure on axial eye length and lens position. Eye (Lond). 2008; 22: 657–661.
Read SA, Collins MJ, Annis-Brown T, et al. The short-term influence of elevated intraocular pressure on axial length. Ophthalmic Physiol Opt. 2011; 31: 398–403.
Chakraborty R, Read SA, Collins MJ. Diurnal variations in axial length, choroidal thickness, intraocular pressure, and ocular biometrics. Invest Ophthalmol Vis Sci. 2011; 52: 5121–5129.
Jansson F. Determination of the axis length of the eye roentgenologically and by ultrasound. Acta ophthalmologica. 1963; 41: 236–246.
Mundt GHJr, Hughes WFJr. Ultrasonics in ocular diagnosis. Am J Ophthalmol. 1956; 41: 488–498.
Luo HD, Gazzard G, Fong A, et al. Myopia, axial length, and OCT characteristics of the macula in Singaporean children. Invest Ophthalmol Vis Sci. 2006; 47: 2773–2781.
Saw SM, Zhang MZ, Hong RZ, Fu ZF, Pang MH, Tan DT. Near-work activity, night-lights, and myopia in the Singapore-China study. Arch Ophthalmol. 2002; 120: 620–627.
Olsen T. The accuracy of ultrasonic determination of axial length in pseudophakic eyes. Acta ophthalmologica. 1989; 67: 141–144.
Trivedi RH, Wilson ME. Axial length measurements by contact and immersion techniques in pediatric eyes with cataract. Ophthalmology. 2011; 118: 498–502.
Hussin HM, Spry PG, Majid MA, Gouws P. Reliability and validity of the partial coherence interferometry for measurement of ocular axial length in children. Eye (Lond). 2006; 20: 1021–1024.
Chan B, Cho P, Cheung SW. Repeatability and agreement of two A-scan ultrasonic biometers and IOLMaster in non-orthokeratology participants and post-orthokeratology children. Clin Exp Optom. 2006; 89: 160–168.
Rudnicka AR, Steele CF, Crabb DP, Edgar DF. Repeatability, reproducibility and intersession variability of the Allergan Humphrey ultrasonic biometer. Acta Ophthalmol. 1992; 70: 327–334.
Findl O, Kriechbaum K, Sacu S, et al. Influence of operator experience on the performance of ultrasound biometry compared to optical biometry before cataract surgery. J Cataract Refract Surg. 2003; 29: 1950–1955.
Hitzenberger CK. Optical measurement of the axial eye length by laser Doppler interferometry. Invest Ophthalmol Vis Sci. 1991; 32: 616–624.
Hitzenberger CK, Drexler W, Dolezal C, et al. Measurement of the axial length of cataract eyes by laser Doppler interferometry. Invest Ophthalmol Vis Sci. 1993; 34: 1886–1893.
Atchison DA, Smith G. Possible errors in determining axial length changes during accommodation with the IOLMaster. Optom Vis Sci. 2004; 81: 283–286.
Drexler W, Findl O, Menapace R, et al. Partial coherence interferometry: a novel approach to biometry in cataract surgery. Am J Ophthalmol. 1998; 126: 524–534.
Haigis W, Lege B, Miller N, Schneider B. Comparison of immersion ultrasound biometry and partial coherence interferometry for intraocular lens calculation according to Haigis. Graefes Arch Clin Exp Ophthalmol. 2000; 238: 765–773.
Cruysberg LP, Doors M, Verbakel F, Berendschot TT, De Brabander J, Nuijts RM. Evaluation of the Lenstar LS 900 non-contact biometer. Br J Ophthalmol. 2010; 94: 106–110.
Huang J, Savini G, Li J, et al. Evaluation of a new optical biometry device for measurements of ocular components and its comparison with IOLMaster. Br J Ophthalmol. 2014; 98: 1277–1281.
Mandal P, Berrow EJ, Naroo SA, et al. Validity and repeatability of the Aladdin ocular biometer. Br J Ophthalmol. 2014; 98: 256–258.
Ventura BV, Ventura MC, Wang L, Koch DD, Weikert MP. Comparison of biometry and intraocular lens power calculation performed by a new optical biometry device and a reference biometer. J Cataract Refract Surg. 2017; 43: 74–79.
Shajari M, Cremonese C, Petermann K, Singh P, Muller M, Kohnen T. Comparison of axial length, corneal curvature, and anterior chamber depth measurements of 2 recently introduced devices to a known biometer. Am J Ophthalmol. 2017; 178: 58–64.
Wojtkowski M, Leitgeb R, Kowalczyk A, Bajraszewski T, Fercher AF. In vivo human retinal imaging by Fourier domain optical coherence tomography. J Biomed Opt. 2002; 7: 457–463.
Dai C, Zhou C, Fan S, et al. Optical coherence tomography for whole eye segment imaging. Opt Express. 2012; 20: 6109–6115.
Zhong J, Tao A, Xu Z, et al. Whole eye axial biometry during accommodation using ultra-long scan depth optical coherence tomography. Am J Ophthalmol. 2014; 157: 1064–1069.
Ruggeri M, Uhlhorn SR, De Freitas C, Ho A, Manns F, Parel JM. Imaging and full-length biometry of the eye during accommodation using spectral domain OCT with an optical switch. Biomed Opt Express. 2012; 3: 1506–1520.
Grulkowski I, Liu JJ, Potsaid B, et al. Retinal, anterior segment and full eye imaging using ultrahigh speed swept source OCT with vertical-cavity surface emitting lasers. Biomed Opt Express. 2012; 3: 2733–2751.
Kunert KS, Peter M, Blum M, et al. Repeatability and agreement in optical biometry of a new swept-source optical coherence tomography-based biometer versus partial coherence interferometry and optical low-coherence reflectometry. J Cataract Refract Surg. 2016; 42: 76–83.
Shammas HJ, Ortiz S, Shammas MC, Kim SH, Chong C. Biometry measurements using a new large-coherence-length swept-source optical coherence tomographer. J Cataract Refract. Surg. 2016; 42: 50–61.
Huang J, Savini G, Hoffer KJ, et al. Repeatability and interobserver reproducibility of a new optical biometer based on swept-source optical coherence tomography and comparison with IOLMaster. Br J Ophthalmol. 2017; 101: 493–498.
McAlinden C, Wang Q, Pesudovs K, et al. Axial length measurement failure rates with the IOLMaster and Lenstar LS 900 in eyes with cataract. PLoS One. 2015; 10: e0128929.
Sankaridurg P, He X, Naduvilath T, et al. Comparison of noncycloplegic and cycloplegic autorefraction in categorizing refractive error data in children. Acta Ophthalmol. 2017; 95: e633–e640.
Twelker JD, Mutti DO. Retinoscopy in infants using a near noncycloplegic technique, cycloplegia with tropicamide 1%, and cycloplegia with cyclopentolate 1%. Optom Vis Sci. 2001; 78: 215–222.
Yazdani N, Sadeghi R, Momeni-Moghaddam H, Zarifmahmoudi L, Ehsaei A. Comparison of cyclopentolate versus tropicamide cycloplegia: a systematic review and meta-analysis. J Optom. 2018; 11: 135–143.
Mutti DO, Zadnik K, Egashira S, Kish L, Twelker JD, Adams AJ. The effect of cycloplegia on measurement of the ocular components. Invest Ophthalmol Vis Sci. 1994; 35: 515–527.
Swarbrick HA, Alharbi A, Watt K, Lum E, Kang P. Myopia control during orthokeratology lens wear in children using a novel study design. Ophthalmology. 2015; 122: 620–630.
Ward PA, Charman WN. Measurements of cycloplegia and mydriasis induced by three common ophthalmic drugs. Clin Exp Optom. 1986; 69: 62–70.
Lovasik JV, Kergoat H. Time course of cycloplegia induced by a new phenylephrine-tropicamide combination drug. Optom Vis Sci. 1990; 67: 352–358.
Lee TT, Cho P. Repeatability of relative peripheral refraction in untreated and orthokeratology-treated eyes. Optom Vis Sci. 2012; 89: 1477–1486.
Moore KE, Berntsen DA. Central and peripheral autorefraction repeatability in normal eyes. Optom Vis Sci. 2014; 91: 1106–1112.
Pesudovs K, Parker KE, Cheng H, Applegate RA. The precision of wavefront refraction compared to participantive refraction and autorefraction. Optom Vis Sci. 2007; 84: 387–392.
Sheppard AL, Davies LN. Clinical evaluation of the Grand Seiko Auto Ref/Keratometer WAM-5500. Ophthalmic Physiol Opt. 2010; 30: 143–151.
Davies LN, Mallen EA, Wolffsohn JS, Gilmartin B. Clinical evaluation of the Shin-Nippon NVision-K 5001/Grand Seiko WR-5100K autorefractor. Optom Vis Sci. 2003; 80: 320–324.
Mallen EA, Gilmartin B, Wolffsohn JS, Tsujimura S. Clinical evaluation of the Shin-Nippon SRW-5000 autorefractor in adults: an update. Ophthalmic Physiol Opt. 2015; 35: 622–627.
Cheng X, Himebaugh NL, Kollbaum PS, Thibos LN, Bradley A. Validation of a clinical Shack-Hartmann aberrometer. Optom Vis Sci. 2003; 80: 587–595.
Cheng X, Himebaugh NL, Kollbaum PS, Thibos LN, Bradley A. Test-retest reliability of clinical Shack-Hartmann measurements. Invest Ophthalmol Vis Sci. 2004; 45: 351–360.
Iskander DR, Nam J, Thibos LN. The statistics of refractive error maps: managing wavefront aberration analysis without Zernike polynomials. Ophthalmic Physiol Opt. 2009; 29: 292–299.
Campbell MC, Bobier WR, Roorda A. Effect of monochromatic aberrations on photorefractive patterns. J Opt Soc Am A Opt Image Sci Vis. 1995; 12: 1637–1646.
Roorda A, Bobier WR. Geometrical technique to determine the influence of monochromatic aberrations on retinoscopy. J Opt Soc Am A Opt Image Sci Vis. 1996; 13: 3–11.
Bradley A, Xu R, Thibos L, Marin G, Hernandez M. Influence of spherical aberration, stimulus spatial frequency, and pupil apodisation on participantive refractions. Ophthalmic Physiol Opt. 2014; 34: 309–320.
Chamberlain P, Back A, Jones L, et al. Parental perspectives on their child wearing daily disposable soft contact lenses in a multicentre clinical study. Presented at: the American Academy of Optometry Annual Meeting. Chicago, Illinois; 2017: program 165325.
Chamberlain P, Back A, Woods J, et al. Wearer experience and participantive responses with a dual-focus myopia control soft contact lens. Presented at: the American Academy of Optometry Annual Meeting. Chicago, Illinois; 2017: program 165326.
Back A, Grant T, Hine N, Holden BA. Twelve-month success rates with a hydrogel diffractive bifocal contact lens. Optom Vis Sci. 1992; 69: 941–947.
Martin JA, Roorda A. Predicting and assessing visual performance with multizone bifocal contact lenses. Optom Vis Sci. 2003; 80: 812–819.
Charman WN, Walsh G. Retinal image quality with different designs of bifocal contact lens. Cont Lens Anterior Eye. 1986; 9: 13–19.
Kollbaum PS, Dietmeier BM, Jansen ME, Rickert ME. Quantification of ghosting produced with presbyopic contact lens correction. Eye Contact Lens. 2012; 38: 252–259.
Tein J-Y, Roosa MW, Michaels M . Agreement between parent and child reports on parental behaviors. J Marr Fam. 1994; 56: 341–355.
Upton P, Lawford J, Eiser C. Parent–child agreement across child health-related quality of life instruments: a review of the literature. Qual Life Res. 2008; 17: 895.
Pullar T, Kumar S, Feely M. Compliance in clinical trials. Ann Rheum Dis. 1989; 48: 871–875.
Robiner WN. Enhancing adherence in clinical research. Contemp Clin Trials. 2005; 26: 59–77.
Czobor P, Skolnick P. The secrets of a successful clinical trial: compliance, compliance, and compliance. Mol Interv. 2011; 11: 107–110.
Skolnick P, Basile AS. Triple reuptake inhibitors (“broad spectrum” antidepressants). CNS Neurol Disord Drug Targets. 2007; 6: 141–149.
Smith DL. Patient nonadherence in clinical trials: could there be a link to postmarketing patient safety? Drug Inf J. 2012; 46: 27–34.
Rand CS, Wise RA, Nides M, et al. Metered-dose inhaler adherence in a clinical trial. Am Rev Respir Dis. 1992; 146: 1559–1564.
Jonasson G, Carlsen KH, Mowinckel P. Asthma drug adherence in a long term clinical trial. Arch Dis Child. 2000; 83: 330–333.
Jones-Jordan LA, Sinnott LT, Cotter SA, et al. Time outdoors, visual activity, and myopia progression in juvenile-onset myopes. Invest Ophthalmol Vis Sci. 2012; 53: 7169–7175.
Saw SM, Shankar A, Tan SB, et al. A cohort study of incident myopia in Singaporean children. Invest Ophthalmol Vis Sci. 2006; 47: 1839–1844.
Stone AA, Shiffman S, Schwartz JE, Broderick JE, Hufford MR. Patient non-compliance with paper diaries. BMJ. 2002; 324: 1193–1194.
Lester RT, Ritvo P, Mills EJ, et al. Effects of a mobile phone short message service on antiretroviral treatment adherence in Kenya (WelTel Kenya1): a randomised trial. Lancet. 2010; 376: 1838–1845.
Miloh T, Annunziato R, Arnon R, et al. Improved adherence and outcomes for pediatric liver transplant recipients by using text messaging. Pediatrics. 2009; 124: e844–e850.
Vervloet M, Linn AJ, van Weert JC, de Bakker DH, Bouvy ML, van Dijk L. The effectiveness of interventions using electronic reminders to improve adherence to chronic medication: a systematic review of the literature. J Am Med Inform Assoc. 2012; 19: 696–704.
Morgan PB, Maldonado-Codina C, Chatterjee N, Moody KL. Elicitation of participantive responses via SMS (text) messaging in contact lens clincial trials. Optom Vis Sci. 2007; 84 E0754143.
Woods CA, Dumbleton K, Jones L, Fonn D. Patient use of smartphones to communicate participantive data in clinical trials. Optom Vis Sci. 2011; 88: 290–294.
Merriam-Webster. Gamification. Available at: https://www.merriam-webster.com/dictionary/gamification. Accessed February 7, 2019.
King D, Greaves F, Exeter C, Darzi A. ‘Gamification': influencing health behaviours with games. J R Soc Med. 2013; 106: 76–78.
Primack BA, Carroll MV, McNamara M, et al. Role of video games in improving health-related outcomes: a systematic review. Am J Prev Med. 2012; 42: 630–638.
Theng Y-L, Lee JWY, Patinadan PV, Foo SSB. The use of videogames, gamification, and virtual environments in the self-management of diabetes: a systematic review of evidence. Games Health J. 2015; 4: 352–361.
Rowbotham MC, Astin J, Greene K, Cummings SR. Interactive informed consent: randomized comparison with paper consents. PLoS One. 2013; 8: e58603.
Comstock J. Cyberdoctor Takes New Angle on Medication Adherence. Available at: http://www.mobihealthnews.com/26182/cyberdoctor-takes-new-angle-on-medication-adherence. Accessed February 7, 2019.
Andrews JEM, Moore JB. Mobile technology in human research. J Clin Res Best Pract. 2015; 11. Available at: https://www.firstclinical.com/journal/2015/1502_Mobile.pdf. Accessed February 7, 2019.
Research2Guidance. Mobile Health App Economics: How Digital Intruders are Taking Over the Healthcare Market. Available at: https://research2guidance.com/wp-content/uploads/2017/10/1-mHealth-Status-And-Trends-Reports.pdf. https://research2guidance.com/wp-content/uploads/2017/10/1-mHealth-Status-And-Trends-Reports.pdf. Accessed February 7, 2019.
Verkicharla PK, Ramamurthy D, Nguyen QD, et al. Development of the FitSight fitness tracker to increase time outdoors to prevent myopia. Trans Vis Sci Tech. 2017; 6 (3): 20.
Dharani R, Lee CF, Theng ZX, et al. Comparison of measurements of time outdoors and light levels as risk factors for myopia in young Singapore children. Eye (Lond). 2012; 26: 911–918.
Gross D, Fogg L. Clinical trials in the 21st century: the case for participant-centered research. Res Nurs Health. 2001; 24: 530–539.
Gul RB, Ali PA. Clinical trials: the challenge of recruitment and retention of participants. J Clin Nurs. 2010; 19: 227–233.
Comprehensive Working Group on Informed Consent in Cancer Clinical Trials. Recommendations for the Development of Informed Consent Documents for Cancer Clinical Trials. Bethesda, MD: National Cancer Institute; 1998.
Roter DL, Rudd RE, Comings J. Patient literacy. A barrier to quality of care. J Gen Intern Med. 1998; 13: 850–851.
Young DR, Hooker DT, Freeberg FE. Informed consent documents: increasing comprehension by reducing reading level. IRB. 1990; 12: 1–5.
Davis TC, Holcombe RF, Berkel HJ, Pramanik S, Divers SG. Informed consent for clinical trials: a comparative study of standard versus simplified forms. J Natl Cancer Inst. 1998; 90: 668–674.
Young T. On the mechanism of the eye. Phil Trans Roy Soc A. 1801; 91 (part 1): 23–88.
Hoogerheide J, Rempt F, Hoogenboom WP. Acquired myopia in young pilots. Ophthalmologica. 1971; 163: 209–215.
Hung LF, Crawford ML, Smith EL. Spectacle lenses alter eye growth and the refractive status of young monkeys. Nat Med. 1995; 1: 761–765.
Whatham AR, Judge SJ. Compensatory changes in eye growth and refraction induced by daily wear of soft contact lenses in young marmosets. Vision Res. 2001; 41: 267–273.
Smith EL, Ramamirtham R, Qiao-Grider Y, et al. Effects of foveal ablation on emmetropization and form-deprivation myopia. Invest Ophthalmol Vis Sci. 2007; 48: 3914–3922.
Smith EL, Hung LF, Huang J, Blasdel TL, Humbird TL, Bockhorst KH. Effects of optical defocus on refractive development in monkeys: evidence for local, regionally selective mechanisms. Invest Ophthalmol Vis Sci. 2010; 51: 3864–3873.
Smith EL, Kee CS, Ramamirtham R, Qiao-Grider Y, Hung LF. Peripheral vision can influence eye growth and refractive development in infant monkeys. Invest Ophthalmol Vis Sci. 2005; 46: 3965–3972.
Wallman J, Winawer J. Homeostasis of eye growth and the question of myopia. Neuron. 2004; 43: 447–468.
Lundström L, Rosén R. Peripheral aberrations. In: Handbook of Visual Optics. Fundamentals and Eye Optics. Vol. 1. London: CRC Press; 2017: 313–335.
Thibos LN, Wheeler W, Horner D. Power vectors: an application of Fourier analysis to the description and statistical analysis of refractive error. Optom Vis Sci. 1997; 74: 367–375.
Atchison DA, Rosén R. The possible role of peripheral refraction in development of myopia. Optom Vis Sci. 2016; 93: 1042–1044.
Lee T-T, Cho P. Relative peripheral refraction in children: twelve month changes in eyes with different ametropias. Ophthalmic Physiol Opt. 2013; 33: 283–293.
Sng CC, Lin XY, Gazzard G, et al. Change in peripheral refraction over time in Singapore Chinese children. Invest Ophthalmol Vis Sci. 2011; 52: 7880–7887.
Rotolo M, Montani G, Martin R. Myopia onset and role of peripheral refraction Clinical Optometry. 2017; 9: 105–111.
Mathur A, Atchison DA. Peripheral refraction patterns out to large field angles. Optom Vis Sci. 2013; 90: 140–147.
Rosén R, Jaeken B, Lindskoog Petterson A, Artal P, Unsbo P, Lundström L. Evaluating the peripheral optical effect of multifocal contact lenses. Ophthalmic Physiol Opt. 2012; 32: 527–534.
Atchison DA, Pritchard N, Schmid KL. Peripheral refraction along the horizontal and vertical visual fields in myopia. Vision Res. 2006; 46: 1450–1458.
Lundström L, Gustafsson J, Unsbo P. Population distribution of wavefront aberrations in the peripheral human eye. J Opt Soc Am A. 2009; 26: 2192–2198.
Berntsen DA, Barr CD, Mutti DO, Zadnik K. Peripheral defocus and myopia progression in myopic children randomly assigned to wear single vision and progressive addition lenses. Invest Ophthalmol Vis Sci. 2013; 54: 5761–5770.
Backhouse S, Fox S, Ibrahim B, Phillips JR. Peripheral refraction in myopia corrected with spectacles versus contact lenses. Ophthalmic Physiol Opt. 2012; 32: 294–303.
Berntsen DA, Kramer CE. Peripheral defocus with spherical and multifocal soft contact lenses. Optom Vis Sci. 2013; 90: 1215–1224.
Kang P, Swarbrick H. Peripheral refraction in myopic children wearing orthokeratology and gas-permeable lenses. Optom Vis Sci. 2011; 88: 476–482.
Fedtke C, Ehrmann K, Holden BA. A review of peripheral refraction techniques. Optom Vis Sci. 2009; 86: 429–446.
Lundström L, Gustafsson J, Svensson I, Unsbo P. Assessment of objective and participantive eccentric refraction. Optom Vis Sci. 2005; 82: 298–306.
Millodot M, Lamont A. Letter: refraction of the periphery of the eye. J Opt Soc Am. 1974; 64: 110–111.
Wang YZ, Thibos LN, Lopez N, Salmon T, Bradley A. Participantive refraction of the peripheral field using contrast detection acuity. J Am Optom Assoc. 1996; 67: 584–589.
Ames A, Proctor CA. Dioptrics of the eye. J Opt Soc Am. 1921; 5: 22–84.
Zadnik K, Mutti DO, Adams AJ. The repeatability of measurement of the ocular components. Invest Ophthalmol Vis Sci. 1992; 33: 2325–2333.
Ferree CE, Rand G, Hardy C. Refraction for the peripheral field of vision. Arch Ophthalmol. 1931; 5: 717–731.
Ferree CE, Rand G, Hardy C. Refractive asymmetry in the temporal and nasal halves of the visual field. Am J Ophthalmol. 1932; 15: 513–522.
Seidemann A, Schaeffel F, Guirao A, Lopez-Gil N, Artal P. Peripheral refractive errors in myopic, emmetropic, and hyperopic young participants. J Opt Soc Am A. 2002; 19: 2363–2373.
Lundström L, Mira-Agudelo A, Artal P. Peripheral optical errors and their change with accommodation differ between emmetropic and myopic eyes. J Vis. 2009; 9: 17.
Radhakrishnan H, Charman WN. Peripheral refraction measurement: does it matter if one turns the eye or the head? Ophthalmic Physiol Opt. 2008; 28: 73–82.
Mathur A, Atchison DA, Kasthurirangan S, et al. The influence of oblique viewing on axial and peripheral refraction for emmetropes and myopes. Ophthalmic Physiol Opt. 2009; 29: 155–161.
El-Nimri NW, Walline JJ. Centration and decentration of contact lenses during peripheral gaze. Optom Vis Sci. 2017; 94: 1029–1035.
Jaeken B, Lundström L, Artal P. Fast scanning peripheral wave-front sensor for the human eye. Opt Express. 2011; 19: 7903–7913.
Fedtke C, Ehrmann K, Falk D, Bakaraju RC, Holden BA. The BHVI-EyeMapper: peripheral refraction and aberration profiles. Optom Vis Sci. 2014; 91: 1199–1207.
Liu T, Sreenivasan V, Thibos LN. Uniformity of accommodation across the visual field. J Vis. 2016; 16: 6.
Altoaimi BH, Kollbaum P, Meyer D, Bradley A. Experimental investigation of accommodation in eyes fit with multifocal contact lenses using a clinical auto-refractor. Ophthalmic Physiol Opt. 2018; 38: 152–163.
Ma L, Atchison DA, Charman WN. Off-axis refraction and aberrations following conventional laser in situ keratomileusis. J Cataract Refract Surg. 2005; 31: 489–498.
Queirós A, Villa-Collar C, Jorge J, Gutiérrez AR, González-Meijome JM. Peripheral refraction in myopic eyes after LASIK surgery. Optom Vis Sci. 2012; 89: 977–983.
Mathur A, Atchison DA. Effect of orthokeratology on peripheral aberrations of the eye. Optom Vis Sci. 2009; 86: 476–484.
Queiros A, Gonzalez-Meijome JM, Jorge J, Villa-Collar C, Gutierrez AR. Peripheral refraction in myopic patients after orthokeratology. Optom Vis Sci. 2010; 87: 323–329.
Kang P, Swarbrick H. Time course of the effects of orthokeratology on peripheral refraction and corneal topography. Ophthalmic Physiol Opt. 2013; 33: 277–282.
Berntsen DA, Mutti DO, Zadnik K. Study of theories about myopia progression (STAMP) design and baseline data. Optom Vis Sci. 2010; 87: 823–832.
Ehsaei A, Mallen EA, Chisholm CM, Pacey IE. Cross-sectional sample of peripheral refraction in four meridians in myopes and emmetropes. Invest Ophthalmol Vis Sci. 2011; 52: 7574–7585.
Osuagwu UL, Suheimat M, Atchison DA. Mirror symmetry of peripheral monochromatic aberrations in fellow eyes of isomyopes and anisomyopes. Invest Ophthalmol Vis Sci. 2016; 57: 3422–3428.
Charman WN, Mathur A, Scott DH, Hartwig A, Atchison DA. Specifying peripheral aberrations in visual science. J Biomed Opt. 2012; 17: 025004.
Southwell WH. Wave-front estimation from wave-front slope measurements. J Opt Soc Am. 1980; 70: 998–1006.
Nam J, Thibos LN, Iskander DR. Describing ocular aberrations with wavefront vergence maps. Clin Exp Optom. 2009; 92: 194–205.
Lundström L, Rosén R, Baskaran K, et al. Symmetries in peripheral ocular aberrations. J Mod Opt. 2011; 58: 1690–1695.
International Standards Organisation. Ophthalmic Optics and Instruments – Reporting Aberrations of the Human Eye. ISO 24157. Geneva, Switzerland; 2008.
Fedtke C, Ehrmann K, Thomas V, Bakaraju RC. Peripheral refraction and aberration profiles with multifocal lenses. Optom Vis Sci. 2017; 94: 876–885.
Atchison DA, Smith G. Optics of the Human Eye. Oxford: Butterworth-Heinemann; 2000.
Manny RE, Chandler DL, Scheiman MM, et al.; Correction of Myopia Evaluation Trial 2 Study Group for the Pediatric Eye Disease Investigator Group. Accommodative lag by autorefraction and two dynamic retinoscopy methods. Optom Vis Sci. 2009; 86: 233–243.
Koomson NY, Amedo AO, Opoku-Baah C, Ampeh PB, Ankamah E, Bonsu K. Relationship between reduced accommodative lag and myopia progression. Optom Vis Sci. 2016; 93: 683–691.
Li SM, Kang MT, Peng XX, et al. Efficacy of Chinese eye exercises on reducing accommodative lag in school-aged children: a randomized controlled trial. PLoS One. 2015; 10: e0117552.
Nakatsuka C, Hasebe S, Nonaka F, Ohtsuki H. Accommodative lag under habitual seeing conditions: comparison between myopic and emmetropic children. Jpn J Ophthalmol. 2005; 49: 189–194.
Yeo AC, Kang KK, Tang W. Accommodative stimulus response curve of emmetropes and myopes. Ann Acad Med Singapore. 2006; 35: 868–874.
Schilling T, Ohlendorf A, Varnas SR, Wahl S. Peripheral design of progressive addition lenses and the lag of accommodation in myopes. Invest Ophthalmol Vis Sci. 2017; 58: 3319–3324.
Thibos LN, Bradley A, Lopez-Gil N. Modelling the impact of spherical aberration on accommodation. Ophthalmic Physiol Opt. 2013; 33: 482–496.
Kotulak JC, Schor CM. The effects of optical vergence, contrast, and luminance on the accommodative response to spatially bandpass filtered targets. Vision Res. 1987; 27: 1797–1806.
Felipe-Marquez G, Nombela-Palomo M, Cacho I, Nieto-Bona A. Accommodative changes produced in response to overnight orthokeratology. Graefes Arch Clin Exp Ophthalmol. 2015; 253: 619–626.
Wolffsohn JS, Gilmartin B, Mallen EA, Tsujimura S. Continuous recording of accommodation and pupil size using the Shin-Nippon SRW-5000 autorefractor. Ophthalmic Physiol Opt. 2001; 21: 108–113.
Wolffsohn JS, O'Donnell C, Charman WN, Gilmartin B. Simultaneous continuous recording of accommodation and pupil size using the modified Shin-Nippon SRW-5000 autorefractor. Ophthalmic Physiol Opt. 2004; 24: 142–147.
Wolffsohn JS, Ukai K, Gilmartin B. Dynamic measurement of accommodation and pupil size using the portable Grand Seiko FR-5000 autorefractor. Optom Vis Sci. 2006; 83: 306–310.
Bhatt UK, Sheppard AL, Shah S, et al. Design and validity of a miniaturized open-field aberrometer. J Cataract Refract Surg. 2013; 39: 36–40.
Goss DA, Grosvenor T. Rates of childhood myopia progression with bifocals as a function of nearpoint phoria: consistency of three studies. Optom Vis Sci. 1990; 67: 637–640.
Felipe-Marquez G, Nombela-Palomo M, Palomo-Alvarez C, Cacho I, Nieto-Bona A. Binocular function changes produced in response to overnight orthokeratology. Graefes Arch Clin Exp Ophthalmol. 2017; 255: 179–188.
Li SM, Li SY, Liu LR, et al. Full correction and undercorrection of myopia evaluation Trial: design and baseline data of a randomized, controlled, double-blind trial. Clin Exp Ophthalmol. 2013; 41: 329–338.
Hyman L, Gwiazda J, Marsh-Tootle WL, Norton TT, Hussein M; COMET Group. The Correction of Myopia Evaluation Trial (COMET): design and general baseline characteristics. Control Clin Trials. 2001; 22: 573–592.
Cheng D, Woo GC, Drobe B, Schmid KL. Effect of bifocal and prismatic bifocal spectacles on myopia progression in children: three-year results of a randomized clinical trial. JAMA Ophthalmol. 2014; 132: 258–264.
Hasebe S, Nonaka F, Nakatsuka C, Ohtsuki H. Myopia control trial with progressive addition lenses in Japanese schoolchildren: baseline measures of refraction, accommodation, and heterophoria. Jpn J Ophthalmol. 2005; 49: 23–30.
Brown B, Edwards MH, Leung JT. Is esophoria a factor in slowing of myopia by progressive lenses? Optom Vis Sci. 2002; 79: 638–642.
Bao J, Wang Y, Zhuo Z, et al. Influence of progressive addition lenses on reading posture in myopic children. Br J Ophthalmol. 2016; 100: 1114–1117.
Sanker N, Prabhu A, Ray A. A comparison of near-dissociated heterophoria tests in free space. Clin Exp Optom. 2012; 95: 638–642.
Rainey BB, Schroeder TL, Goss DA, Grosvenor TP. Inter-examiner repeatability of heterophoria tests. Optom Vis Sci. 1998; 75: 719–726.
Faria-Ribeiro M, Navarro R, Gonzalez-Meijome JM. Effect of pupil size on wavefront refraction during orthokeratology. Optom Vis Sci. 2016; 93: 1399–1408.
Chia A, Chua WH, Wen L, Fong A, Goon YY, Tan D. Atropine for the treatment of childhood myopia: changes after stopping atropine 0.01%, 0.1% and 0.5%. Am J Ophthalmol. 2014; 157: 451–457.
Fedtke C, Bakaraju RC, Ehrmann K, Chung J, Thomas V, Holden BA. Visual performance of single vision and multifocal contact lenses in non-presbyopic myopic eyes. Cont Lens Anterior Eye. 2016; 39: 38–46.
Gedik S, Koktekir BE, Bakbak B, Gonul S. Comparison of pupil diameter measurement with Lenstar LS 900 and OPD Scan II. Not interchangeable devices. Saudi Med J. 2012; 33: 1239–1240.
Santodomingo-Rubido J, Villa-Collar C, Gilmartin B, Gutierrez-Ortega R. Factors preventing myopia progression with orthokeratology correction. Optom Vis Sci. 2013; 90: 1225–1236.
Holden BA, Fricke TR, Wilson DA, et al. Global prevalence of myopia and high myopia and temporal trends from 2000 through 2050. Ophthalmology. 2016; 11: 25–27.
He M, Zeng J, Liu Y, Xu J, Pokharel GP, Ellwein LB. Refractive error and visual impairment in urban children in southern China. Invest Ophthalmol Vis Sci. 2004; 45: 793–799.
Saw SM, Carkeet A, Chia KS, Stone RA, Tan DT. Component dependent risk factors for ocular parameters in Singapore Chinese children. Ophthalmology. 2002; 109: 2065–2071.
Lin LL, Shih YF, Hsiao CK, Chen CJ. Prevalence of myopia in Taiwanese schoolchildren: 1983 to 2000. Ann Acad Med Singapore. 2004; 33: 27–33.
Klein AP, Duggal P, Lee KE, Klein R, Bailey-Wilson JE, Klein BE. Support for polygenic influences on ocular refractive error. Invest Ophthalmol Vis Sci. 2005; 46: 442–446.
Ip JM, Huynh SC, Robaei D, et al. Ethnic differences in the impact of parental myopia: findings from a population-based study of 12-year-old Australian children. Invest Ophthalmol Vis Sci. 2007; 48: 2520–2528.
Ip JM, Rose KA, Morgan IG, Burlutsky G, Mitchell P. Myopia and the urban environment: findings in a sample of 12-year-old Australian school children. Invest Ophthalmol Vis Sci. 2008; 49: 3858–3863.
Wu HM, Seet B, Yap EP, Saw SM, Lim TH, Chia KS. Does education explain ethnic differences in myopia prevalence? A population-based study of young adult males in Singapore. Optom Vis Sci. 2001; 78: 234–239.
Dolgin E. The myopia boom. Nature. 2015; 519: 276–278.
Troilo D, Smith EL III, Nickla DL, et al. IMI – Report on Experimental Models of Emmetropization and Myopia. Invest Ophthalmol Vis Sci. 2019; 60: M31–M88.
Adams DW, McBrien NA. Prevalence of myopia and myopic progression in a population of clinical microscopists. Optom Vis Sci. 1992; 69: 467–473.
Barrett BT, Bradley A, Candy TR. The relationship between anisometropia and amblyopia. Prog Retin Eye Res. 2013; 36: 120–158.
Wildsoet C, Chia A, Cho P, et al. IMI – Interventions for Controlling Myopia Onset and Progression Report. Invest Ophthalmol Vis Sci. 2019; 60: M106–M131.
Li Y, Liu J, Qi P. The increasing prevalence of myopia in junior high school students in the Haidian District of Beijing, China: a 10-year population-based survey. BMC Ophthalmol. 2017; 17: 88.
Mutti DO, Mitchell GL, Moeschberger ML, Jones LA, Zadnik K. Parental myopia, near work, school achievement, and children's refractive error. Invest Ophthalmol Vis Sci. 2002; 43: 3633–3640.
Rose KA, Morgan IG, Ip J, et al. Outdoor activity reduces the prevalence of myopia in children. Ophthalmology. 2008; 115: 1279–1285.
French AN, Morgan IG, Mitchell P, Rose KA. Risk factors for incident myopia in Australian schoolchildren: the Sydney adolescent vascular and eye study. Ophthalmology. 2013; 120: 2100–2108.
Xiong S, Sankaridurg P, Naduvilath T, et al. Time spent in outdoor activities in relation to myopia prevention and control: a meta-analysis and systematic review. Acta Ophthalmol. 2017; 95: 551–566.
Alvarez AA, Wildsoet CF. Quantifying light exposure patterns in young adult students. J Mod Opt. 2013; 60: 1200–1208.
Walline JJ, Lindsley K, Vedula SS, Cotter SA, Mutti DO, Twelker JD. Interventions to slow progression of myopia in children. Cochrane Database Syst Rev. 2011; 12:CD004916.
Read SA, Collins MJ, Vincent SJ. Light exposure and physical activity in myopic and emmetropic children. Optom Vis Sci. 2014; 91: 330–341.
Cooper AR, Page AS, Wheeler BW, Hillsdon M, Griew P, Jago R. Patterns of GPS measured time outdoors after school and objective physical activity in English children: the PEACH project. Int J Behav Nutr Phys Act. 2010; 7: 31.
Schmid KL, Leyden K, Chiu YH, et al. Assessment of daily light and ultraviolet exposure in young adults. Optom Vis Sci. 2013; 90: 148–155.
Read SA, Collins MJ, Vincent SJ. Light exposure and eye growth in childhood. Invest Ophthalmol Vis Sci. 2015; 56: 6779–6787.
Ostrin LA. Objectively measured light exposure in emmetropic and myopic adults. Optom Vis Sci. 2017; 94: 229–238.
Ulaganathan S, Read SA, Collins MJ, Vincent SJ. Measurement duration and frequency impact objective light exposure measures. Optom Vis Sci. 2017; 94: 588–597.
Sprague WW, Cooper EA, Reissier S, Yellapragada B, Banks MS. The natural statistics of blur. J Vis. 2016; 16 (10): 23.
Jaskulski M, Marin-Franch I, Bernal-Molina P, Lopez-Gil N. The effect of longitudinal chromatic aberration on the lag of accommodation and depth of field. Ophthalmic Physiol Opt. 2016; 36: 657–663.
Garcia MG, Ohlendorf A, Schaeffel F, Wahl S. Dioptric defocus maps across the visual field for different indoor environments. Biomed Opt Express. 2018; 9: 347–359.
He M, Xiang F, Zeng Y, et al. Effect of time spent outdoors at school on the development of myopia among children in China: a randomized clinical trial. JAMA Ophthalmol. 2015; 314: 1142–1148.
Wu PC, Tsai CL, Wu HL, Yang YH, Kuo HK. Outdoor activity during class recess reduces myopia onset and progression in school children. Ophthalmology. 2013; 120: 1080–1085.
Jin JX, Hua WJ, Jiang X, et al. Effect of outdoor activity on myopia onset and progression in school-aged children in northeast China: the Sujiatun Eye Care Study. BMC Ophthalmol. 2015; 15: 73.
Cotter SA. Management of childhood hyperopia: a pediatric optometrist's perspective. Optom Vis Sci. 2007; 84: 103–109.
Mutti DO, Hayes JR, Mitchell GL, et al. Refractive error, axial length, and relative peripheral refractive error before and after the onset of myopia. Invest Ophthalmol Vis Sci. 2007; 48: 2510–2519.
Godar DE, Wengraitis SP, Shreffler J, Sliney DH. UV doses of Americans. Photochem Photobiol. 2001; 73: 621–629.
Vanos JK, McKercher GR, Naughton K, Lochbaum M. Schoolyard shade and sun exposure: assessment of personal monitoring during children's physical activity. Photochem Photobiol. 2017; 93: 1123–1132.
Jones LA, Sinnott LT, Mutti DO, Mitchell GL, Moeschberger ML, Zadnik K. Parental history of myopia, sports and outdoor activities, and future myopia. Invest Ophthalmol Vis Sci. 2007; 48: 3524–3532.
Lundberg K, Suhr Thykjaer A, Sogaard Hansen R, et al. Physical activity and myopia in Danish children – The CHAMPS Eye Study. Acta Ophthalmol. 2017; 3: 13513.
Chang SW, Tsai IL, Hu FR, Lin LL, Shih YF. The cornea in young myopic adults. Br J Ophthalmol. 2001; 85: 916–920.
Goss DA, Van Veen HG, Rainey BB, Feng B. Ocular components measured by keratometry, phakometry, and ultrasonography in emmetropic and myopic optometry students. Optom Vis Sci. 1997; 74: 489–495.
Fledelius HC, Goldschmidt E. Oculometry findings in high myopia at adult age: considerations based on oculometric follow-up data over 28 years in a cohort-based Danish high-myopia series. Acta Ophthalmol. 2010; 88: 472–478.
Park SH, Park KH, Kim JM, Choi CY. Relation between axial length and ocular parameters. Ophthalmologica. 2010; 224: 188–193.
Ucakhan OO, Gesoglu P, Ozkan M, Kanpolat A. Corneal elevation and thickness in relation to the refractive status measured with the Pentacam Scheimpflug system. J Cataract Refract Surg. 2008; 34: 1900–1905.
Cho P, Lam C. Factors affecting the central corneal thickness of Hong Kong-Chinese. Curr Eye Res. 1999; 18: 368–374.
Carney LG, Mainstone JC, Henderson BA. Corneal topography and myopia. A cross-sectional study. Invest Ophthalmol Vis Sci. 1997; 38: 311–320.
Hosny M, Alio JL, Claramonte P, Attia WH, Perez-Santonja JJ. Relationship between anterior chamber depth, refractive state, corneal diameter, and axial length. J Refract Surg. 2000; 16: 336–340.
Orucoglu F, Akman M, Onal S. Analysis of age, refractive error and gender related changes of the cornea and the anterior segment of the eye with Scheimpflug imaging. Cont Lens Anterior Eye. 2015; 38: 345–350.
Kasahara K, Maeda N, Fujikado T, et al. Characteristics of higher-order aberrations and anterior segment tomography in patients with pathologic myopia. Int Ophthalmol. 2017; 37: 1279–1288.
Zong Y, Xu Q, Jiang C, Zhu H, Yu J, Sun X. Measurement of and factors associated with the anterior chamber volume in healthy Chinese adults. J Ophthalmol. 2017; 2017: 6762047.
Mutti DO. Hereditary and environmental contributions to emmetropization and myopia. Optom Vis Sci. 2010; 87: 255–259.
Oliveira C, Tello C, Liebmann JM, Ritch R. Ciliary body thickness increases with increasing axial myopia. Am J Ophthalmol. 2005; 140: 324–325.
Muftuoglu O, Hosal BM, Zilelioglu G. Ciliary body thickness in unilateral high axial myopia. Eye (Lond). 2009; 23: 1176–1181.
Lewis HA, Kao CY, Sinnott LT, Bailey MD. Changes in ciliary muscle thickness during accommodation in children. Optom Vis Sci. 2012; 89: 727–737.
Buckhurst H, Gilmartin B, Cubbidge RP, Nagra M, Logan NS. Ocular biometric correlates of ciliary muscle thickness in human myopia. Ophthalmic Physiol Opt. 2013; 33: 294–304.
Sheppard AL, Davies LN. In vivo analysis of ciliary muscle morphologic changes with accommodation and axial ametropia. Invest Ophthalmol Vis Sci. 2010; 51: 6882–6889.
Richdale K, Bullimore MA, Sinnott LT, Zadnik K. The effect of age, accommodation, and refractive error on the adult human eye. Optom Vis Sci. 2016; 93: 3–11.
Malyugin BE, Shpak AA, Pokrovskiy DF. Accommodative changes in anterior chamber depth in patients with high myopia. J Cataract Refract Surg. 2012; 38: 1403–1407.
Tsukiyama J, Miyamoto Y, Higaki S, Fukuda M, Shimomura Y. Changes in the anterior and posterior radii of the corneal curvature and anterior chamber depth by orthokeratology. Eye Contact Lens. 2008; 34: 17–20.
Queiros A, Villa-Collar C, Gutierrez AR, et al. Anterior and posterior corneal elevation after orthokeratology and standard and customized LASIK surgery. Eye Contact Lens. 2011; 37: 354–358.
Gonzalez-Mesa A, Villa-Collar C, Lorente-Velazquez A, Nieto-Bona A. Anterior segment changes produced in response to long-term overnight orthokeratology. Curr Eye Res. 2013; 38: 862–870.
Chen D, Lam AK, Cho P. Posterior corneal curvature change and recovery after 6 months of overnight orthokeratology treatment. Ophthalmic Physiol Opt. 2010; 30: 274–280.
Cheung SW, Cho P. Validity of axial length measurements for monitoring myopic progression in orthokeratology. Invest Ophthalmol Vis Sci. 2013; 54: 1613–1615.
Cheung SW, Cho P. Long-term effect of orthokeratology on the anterior segment length. Cont Lens Anterior Eye. 2016; 39: 262–265.
Zhong Y, Chen Z, Xue F, Miao H, Zhou X. Central and peripheral corneal power change in myopic orthokeratology and its relationship with 2-year axial length change. Invest Ophthalmol Vis Sci. 2015; 56: 4514–4519.
Lam DS, Leung KS, Mohamed S, et al. Regional variations in the relationship between macular thickness measurements and myopia. Invest Ophthalmol Vis Sci. 2007; 48: 376–382.
Read SA, Alonso-Caneiro D, Vincent SJ, Collins MJ. Peripapillary choroidal thickness in childhood. Exp Eye Res. 2015; 135: 164–173.
Samarawickrama C, Mitchell P, Tong L, et al. Myopia-related optic disc and retinal changes in adolescent children from singapore. Ophthalmology. 2011; 118: 2050–2057.
Verkicharla PK, Ohno-Matsui K, Saw SM. Current and predicted demographics of high myopia and an update of its associated pathological changes. Ophthalmic Physiol Opt. 2015; 35: 465–475.
Verkicharla PK, Suheimat M, Schmid KL, Atchison DA. Peripheral refraction, peripheral eye length, and retinal shape in myopia. Optom Vis Sci. 2016; 93: 1072–1078.
Mrejen S, Spaide RF. Optical coherence tomography: imaging of the choroid and beyond. Surv Ophthalmol. 2013; 58: 387–429.
Odell D, Dubis AM, Lever JF, Stepien KE, Carroll J. Assessing errors inherent in OCT-derived macular thickness maps. J Ophthalmol. 2011; 2011: 692574.
Choi JA, Kim JS, Park HY, Park H, Park CK. The foveal position relative to the optic disc and the retinal nerve fiber layer thickness profile in myopia. Invest Ophthalmol Vis Sci. 2014; 55: 1419–1426.
Marmor MF, Kellner U, Lai TY, Melles RB, Mieler WF. Recommendations on screening for chloroquine and hydroxychloroquine retinopathy (2016 revision). Ophthalmology. 2016; 123: 1386–1394.
Luu CD, Lau AM, Koh AH, Tan D. Multifocal electroretinogram in children on atropine treatment for myopia. Br J Ophthalmol. 2005; 89: 151–153.
Kuo AN, Verkicharla PK, McNabb RP, et al. Posterior eye shape measurement with retinal OCT compared to MRI. Invest Ophthalmol Vis Sci. 2016; 57: 196–203.
Verkicharla PK, Mathur A, Mallen EA, Pope JM, Atchison DA. Eye shape and retinal shape, and their relation to peripheral refraction. Ophthalmic Physiol Opt. 2012; 32: 184–199.
Gilmartin B, Nagra M, Logan NS. Shape of the posterior vitreous chamber in human emmetropia and myopia. Invest Ophthalmol Vis Sci. 2013; 54: 7240–7251.
Verkicharla PK, Suheimat M, Pope JM, et al. Validation of a partial coherence interferometry method for estimating retinal shape. Biomed Opt Express. 2015; 6: 3235–3247.
Pope JM, Verkicharla PK, Sepehrband F, Suheimat M, Schmid KL, Atchison DA. Three-dimensional MRI study of the relationship between eye dimensions, retinal shape and myopia. Biomed Opt Express. 2017; 8: 2386–2395.
Atchison DA, Pritchard N, Schmid KL, Scott DH, Jones CE, Pope JM. Shape of the retinal surface in emmetropia and myopia. Invest Ophthalmol Vis Sci. 2005; 46: 2698–2707.
Curtin BJ. Physiologic vs pathologic myopia: genetics vs environment. Ophthalmology. 1979; 86: 681–691.
Avetisov ES, Savitskaya NF, Vinetskaya MI, Iomdina EN. A study of biochemical and biomechanical qualities of normal and myopic eye sclera in humans of different age groups. Metab Pediatr Syst Ophthalmol. 1983; 7: 183–188.
McBrien NA, Gentle A. Role of the sclera in the development and pathological complications of myopia. Prog Retin Eye Res. 2003; 22: 307–338.
Saka N, Moriyama M, Shimada N, et al. Changes of axial length measured by IOL master during 2 years in eyes of adults with pathologic myopia. Graefes Arch Clin Exp Ophthalmol. 2013; 251: 495–499.
Ho LC, Sigal IA, Jan NJ, et al. Magic angle-enhanced MRI of fibrous microstructures in sclera and cornea with and without intraocular pressure loading. Invest Ophthalmol Vis Sci. 2014; 55: 5662–5672.
Buckhurst HD, Gilmartin B, Cubbidge RP, Logan NS. Measurement of scleral thickness in humans using anterior segment optical coherent tomography. PLoS One. 2015; 10: e0132902.
Patel H, Gilmartin B, Cubbidge RP, Logan NS. In vivo measurement of regional variation in anterior scleral resistance to Schiotz indentation. Ophthalmic Physiol Opt. 2011; 31: 437–443.
Hommer A, Fuchsjager-Mayrl G, Resch H, Vass C, Garhofer G, Schmetterer L. Estimation of ocular rigidity based on measurement of pulse amplitude using pneumotonometry and fundus pulse using laser interferometry in glaucoma. Invest Ophthalmol Vis Sci. 2008; 49: 4046–4050.
Detorakis ET, Drakonaki EE, Tsilimbaris MK, Pallikaris IG, Giarmenitis S. Real-time ultrasound elastographic imaging of ocular and periocular tissues: a feasibility study. Ophthalmic Surg Lasers Imaging. 2010; 41: 135–141.
Sergienko NM, Shargorogska I. The scleral rigidity of eyes with different refractions. Graefes Arch Clin Exp Ophthalmol. 2012; 250: 1009–1012.
Ebneter A, Wagels B, Zinkernagel MS. Non-invasive biometric assessment of ocular rigidity in glaucoma patients and controls. Eye (Lond). 2009; 23: 606–611.
Detorakis ET, Pallikaris IG. Ocular rigidity: biomechanical role, in vivo measurements and clinical significance. Clin Exp Ophthalmol. 2013; 41: 73–81.
McMonnies CW. An examination of the relation between intraocular pressure, fundal stretching and myopic pathology. Clin Exp Optom. 2016; 99: 113–119.
Liu TX, Wang Z. Collagen crosslinking of porcine sclera using genipin. Acta Ophthalmol. 2013; 91: e253–e257.
Dotan A, Kremer I, Gal-Or O, et al. Scleral cross-linking using riboflavin and ultraviolet-A radiation for prevention of axial myopia in a rabbit model. J Vis Exp. 2016; e53201.
Song Y, Congdon N, Li L, et al. Corneal hysteresis and axial length among Chinese secondary school children: the Xichang pediatric refractive error study (X-PRES) report no. 4. Am J Ophthalmol. 2008; 145: 819–826.
Plakitsi A, O'Donnell C, Miranda MA, Charman WN, Radhakrishnan H. Corneal biomechanical properties measured with the Ocular Response Analyser in a myopic population. Ophthalmic Physiol Opt. 2011; 31: 404–412.
Fontes BM, Ambrosio RJr, Alonso RS, Jardim D, Velarde GC, Nose W. Corneal biomechanical metrics in eyes with refraction of −19.00 to +9.00 D in healthy Brazilian patients. J Refract Surg. 2008; 24: 941–945.
Lee R, Chang RT, Wong IY, Lai JS, Lee JW, Singh K. Assessment of corneal biomechanical parameters in myopes and emmetropes using the Corvis ST. Clin Exp Optom. 2016; 99: 157–162.
Chen D, Lam AK, Cho P. A pilot study on the corneal biomechanical changes in short-term orthokeratology. Ophthalmic Physiol Opt. 2009; 29: 464–471.
Gonzalez-Meijome JM, Villa-Collar C, Queiros A, Jorge J, Parafita MA. Pilot study on the influence of corneal biomechanical properties over the short term in response to corneal refractive therapy for myopia. Cornea. 2008; 27: 421–426.
Prasad A, Fry K, Hersh PS. Relationship of age and refraction to central corneal thickness. Cornea. 2011; 30: 553–555.
AlMahmoud T, Priest D, Munger R, Jackson WB. Correlation between refractive error, corneal power, and thickness in a large population with a wide range of ametropia. Invest Ophthalmol Vis Sci. 2011; 52: 1235–1242.
Kang P, Swarbrick H. New perspective on myopia control with orthokeratology. Optom Vis Sci. 2016; 93: 497–503.
Qiu K, Lu X, Zhang R, Wang G, Zhang M. Corneal biomechanics determination in healthy myopic participants. J Ophthalmol. 2016; 2016: 2793516.
Matalia J, Francis M, Gogri P, Panmand P, Matalia H, Roy AS. Correlation of corneal biomechanical stiffness with refractive error and ocular biometry in a pediatric population. Cornea. 2017; 36: 1221–1226.
Figure 1
 
Schematic of considerations that influence the clinically meaningful effect size.
Figure 1
 
Schematic of considerations that influence the clinically meaningful effect size.
Figure 2
 
Spot diagrams for a distance-center bifocal contact lens combined with the Navarro schematic eye,276 as a function of horizontal visual field angle. Out of the eye raytracing, distance power 0D, addition +2D, center zone diameter 2 mm, refractive index 1.43, pupil size 3 mm, back surface of contact lens is that of the cornea at 7.72 mm. Drawn with Zemax OpticStudio 16.5 SP1 (Zemax, LLC, Kirkland, WA, USA).
Figure 2
 
Spot diagrams for a distance-center bifocal contact lens combined with the Navarro schematic eye,276 as a function of horizontal visual field angle. Out of the eye raytracing, distance power 0D, addition +2D, center zone diameter 2 mm, refractive index 1.43, pupil size 3 mm, back surface of contact lens is that of the cornea at 7.72 mm. Drawn with Zemax OpticStudio 16.5 SP1 (Zemax, LLC, Kirkland, WA, USA).
Figure 3
 
Wave aberration maps in the exit pupil plane for a distance-center bifocal contact lens combined with the Navarro schematic eye. Conditions are the same as for Figure 2. Drawn with Zemax OpticStudio 16.5 SP1 (Zemax, LLC).
Figure 3
 
Wave aberration maps in the exit pupil plane for a distance-center bifocal contact lens combined with the Navarro schematic eye. Conditions are the same as for Figure 2. Drawn with Zemax OpticStudio 16.5 SP1 (Zemax, LLC).
Table 1
 
Selection Criteria in Recent Myopia Control Clinical Trials
Table 1
 
Selection Criteria in Recent Myopia Control Clinical Trials
Table 2
 
Typical Inclusion/Exclusion Criteria, Although Should Be Altered to Address Specific Study Hypothesis
Table 2
 
Typical Inclusion/Exclusion Criteria, Although Should Be Altered to Address Specific Study Hypothesis
Table 3
 
Control Group, Randomization, and Masking
Table 3
 
Control Group, Randomization, and Masking
Table 4
 
Sample Size Calculations for Different Modalities of Myopia Control Treatment Based on Axial Length Effect Size
Table 4
 
Sample Size Calculations for Different Modalities of Myopia Control Treatment Based on Axial Length Effect Size
Table 5
 
Expected Minimum Data Set for Each Treatment Modality
Table 5
 
Expected Minimum Data Set for Each Treatment Modality
×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×