Efficacy in myopia control-The impact of rebound.

PURPOSE: When myopia control treatment is discontinued, progression will increase, but does it revert to expected values based on the age and race of the child or does it accelerate further? The latter scenario is considered a rebound. METHODS: A PubMed search was conducted with the words 'rebound' and 'myopia control', identifying further papers from reviews. Inclusion was limited to prospective studies with ≥6 months of treatment, ≥3 months of data following cessation and with axial length data, which allowed calculation of rebound. Nineteen studies were identified, comprising 24 treatment groups. In 10 studies, untreated control children were followed both throughout the treatment and cessation periods, allowing for a concurrent comparison group. In three studies, a control group was followed for 1 or 2 years and thereafter received the treatment under evaluation. Later, treatment ceased in the originally treated children. Finally, six studies were cross-over designs. For these latter two study designs, initial axial elongation and myopia progression in the control group were extrapolated to the cessation period, accounting for annual slowing. Values from durations of <1 year were annualised. RESULTS: The mean annualised rebound was +0.05 ± 0.10 mm and -0.09 ± 0.24 D for axial length and myopia progression, respectively, and these were correlated (r2 = 0.59, p < 0.001). Rebound was associated with 1-year treatment efficacy (r2 = 0.43, p < 0.001). The mean annualised rebound with optical corrections was -0.01 ± 0.03 mm. Five of the six highest rebound values (≥0.14 mm) were from red light therapy and atropine studies. Rebound ranged from +0.03 to +0.14 mm for overnight orthokeratology. CONCLUSIONS: Consistent with previous statements, no evidence for rebound was found for myopia control spectacles and soft contact lenses. Future research should explore the influence of age and magnitude of treatment efficacy on rebound.

Is the Change in Prevalence of High Myopia Compared to That of Myopia Really Disproportionate?

Purpose: It has been noted that, at higher prevalences, the rate of change in the prevalence of high myopia seems to be disproportionately greater compared with the rate of change in the prevalence of myopia. A simple, evidence-based explanation for this relationship is offered. Methods: Using a convenience sample of 41 datasets with prevalence estimates for at least two refractive error thresholds (e.g., -0.50 and -6.00 D) the common slope of the logit vs. refractive threshold was applied to model expected rates of high myopia across the myopia prevalence range and the corresponding ratio of change in high myopia to myopia prevalence. Results: The logit of high myopia is related linearly to the logit of myopia. The ratio of increase in high myopia prevalence to that for myopia prevalence increases with underlying prevalence. For example, an increase in myopia prevalence from 19% to 20% is modelled to be accompanied by a 0.1% increase in the prevalence of high myopia from 1.55% to 1.65%-a ratio of 0.1. Conversely, an increase in myopia prevalence from 79% to 80% is predicted to result in a 1% increase in the prevalence of high myopia from 20.6% to 21.6%-a ratio of 1.0. Conclusions: The increase in the prevalence of high myopia compared with that of myopia as the latter increases is merely a function of the underlying nature of refractive error probability distributions and requires no further investigation as to its origin. Translational Relevance: This study shows how the prevalence of myopia and high myopia are inter-related. A widespread effort to slow myopia progression will affect the prevalence of high myopia but not myopia in general. In contrast, efforts to delay myopia onset will affect both.

Can we really distinguish 'responders' from 'non-responders' to myopia control interventions?

PURPOSE: It is common to hear talk of 'responders' and 'non-responders' with respect to myopia control interventions. We consider the reality of distinguishing these sub-groups using data from the first year of the Low-concentration Atropine for Myopia Progression (LAMP) study. METHODS: The first year of the LAMP study was a robustly designed, placebo-controlled trial of three different low concentrations of atropine using a large sample size (N > 100 randomised to each group). The authors subsequently published mean axial elongation and myopia progression rates by age group. We used these data to calculate efficacy in terms of both absolute reduction in myopic progression and absolute reduction in axial elongation for each of the different atropine concentrations at each age group. We then compared these efficacy data to the overall progression for each of the two progression metrics. RESULTS: Plotting efficacy as a function of overall myopia progression and axial elongation for each of the different atropine concentrations demonstrates the invariant nature of efficacy, in terms of clinically meaningful reduction in progression, despite a substantial range of underlying overall progression. That is, faster progressors-the so-called non-responders-achieved similar reduction in axial elongation and myopia progression as the slower progressors-the so-called responders-within the various atropine treatment groups. CONCLUSION: The use of the terms, responders and non-responders, during myopia progression interventions is not supported by evidence. Those designated as such may simply be slower or faster progressors, who, on average achieve the same benefit from treatment.

Influence of age and race on axial elongation in myopic children: A systematic review and meta-regression.

PURPOSE: Axial elongation is the basis of progression in primary myopia and the preferred metric to monitor its evolution. We conducted a meta-regression to model axial elongation and its associated factors in children with low to moderate myopia. METHODS: A comprehensive electronic systematic search was performed using Ovid Medline, EMBASE, and Cochrane Central Register of Controlled Trials of studies conducted up until October 2021. The mean rate of axial elongation was analyzed using a multivariate linear mixed-effects meta-regression model, with backward stepwise elimination of nonsignificant covariates. The model included three levels of random effects, allowing both prediction and confidence intervals to be estimated. RESULTS: A total of 64 studies with 83 subpopulations and 142 evaluations of mean axial change from baseline met our inclusion criteria and had no missing significant covariates in the final model. A separate analysis including all populations with axial length data (202 evaluations) but missing variance or covariate data produced a similar model to that for the analysis with complete data. The mean axial elongation is 38% greater in Asian children (95% confidence interval, 19 to 61%; p<0.01) compared with non-Asians, but both groups show a 15% decline per year as age increases (95% confidence interval, 12 to 17% p<0.0001). Prediction intervals indicate substantial variability around the axial elongation estimates. CONCLUSIONS: This analysis provides mean values of axial elongation for evaluation of efficacy of myopia control. The broad prediction intervals emphasize the large range of individual axial elongation rates in the population, illustrating the challenge in managing individual children. Interpretation of the analysis is limited by the use of aggregated data rather than individual subject data.

BCLA CLEAR Presbyopia: Definitions.

Presbyopia is often the first sign of ageing experienced by humans. Standardising terminology and adopting it across the BCLA CLEAR Presbyopia reports, improves consistency in the communication of the evidence-based understanding of this universal physiological process. Presbyopia can be functionally and psychologically debilitating, especially for those with poor access to eyecare. Presbyopia was defined as occurring when the physiologically normal age-related reduction in the eye's focusing range reaches a point that, when optimally corrected for far vision, the clarity of vision at near is insufficient to satisfy an individual's requirements. Accommodation is the change in optical power of the eye due to a change in crystalline lens shape and position, whereas pseudo-accommodation is the attainment of functional near vision in an emmetropic or far-corrected eye without changing the refractive power of the eye. Other definitions specific to vision and lenses for presbyopia were also defined. It is recommended that these definitions be consistently adopted in order to standardise future research, clinical evaluations and education.

Myopia control: Seeing beyond efficacy.

SIGNIFICANCE: The availability of a range of effective myopia control modalities enables the clinician to exercise judgment when discussing the treatment plan with the patient and their parents. This article outlines important considerations beyond efficacy.Clinically meaningful myopia control may be attained with some spectacle lenses, select soft contact lenses, some concentrations of atropine, and overnight orthokeratology. Given that satisfactory efficacy can be achieved with a range of modalities, other factors should be considered when deciding upon the best intervention for a given child. Four key factors-compliance, quality of vision, quality of life, and safety-are discussed in this review. Compliance directly impacts efficacy regardless of the modality and is the most important consideration, as it is influenced by quality of vision and comfort. Daily disposal myopia control contact lenses and overnight orthokeratology are generally associated with high compliance, provide better vision-related quality of life than spectacles, and carry a very low risk when used appropriately. A further benefit of overnight orthokeratology is the elimination of a need for optical correction during the day.

Optical interventions for myopia control.

A range of optical interventions have been developed to slow the progression of myopia. This review summarizes key studies and their outcomes. Peer-reviewed, randomized controlled clinical trials of at least 18 months duration were identified. Randomized clinical trials were identified and summarised: 13 for spectacles, 5 for overnight orthokeratology, 5 for soft contact lenses, and 3 for orthokeratology combined with low concentration atropine. Overnight orthokeratology trials were the most consistent with 2-year slowing of axial elongation between 0.24 and 0.32 mm. Other modalities were more variable due to the wide range of optical designs. Among spectacle interventions, progressive addition lenses were the least effective, slowing axial elongation and myopia progression by no more than 0.11 mm and 0.31 D, respectively. In contrast, novel designs with peripheral lenslets slow 2-year elongation and progression by up to 0.35 mm and 0.80 D. Among soft contact lens interventions, medium add concentric bifocals slow 3-year elongation and progression by only 0.07 mm and 0.16 D, while a dual-focus design slows 3-year elongation and progression by 0.28 mm and 0.67 D. In summary, all three optical interventions have the potential to significantly slow myopia progression. Quality of vision is largely unaffected, and safety is satisfactory. Areas of uncertainty include the potential for post-treatment acceleration of progression and the benefit of adding atropine to optical interventions.

Juvenile-onset myopia-who to treat and how to evaluate success.

The risk of eye diseases such as myopic macular degeneration increases with the level of myopia, but there is no safe level of myopia and the burden of lower degrees of myopia remains considerable. Effective treatments are available that slow progression and thus limit the final degree of myopia. In this review, the rationale for slowing progression is summarized, and a case made for treating all myopic children. Measurement of refractive error and axial length is reviewed, stressing the precision of optical biometry, but also the need for cycloplegic autorefraction. The factors influencing progression are considered and the available tools for interpretation of progression rate are discussed. Finally, the need to set attainable treatment goals is emphasized.

Low concentration atropine and myopia: a narrative review of the evidence for United Kingdom based practitioners.

The prevalence of myopia is increasing across the world. Controlling myopia progression would be beneficial to reduce adverse outcomes such as retinal detachment and myopic maculopathy which are associated with increased axial length. Pharmacological control of myopia progression with atropine has been investigated since the 19th century and the benefits of slowing myopia progression are considered against the side-effects of near blur and photophobia. More recently, randomised trials have focused on determining the optimum concentration of atropine leading to low-concentration atropine being used to manage myopia progression by practitioners across the world. Currently, in the United Kingdom, there is no licensed pharmacological intervention for myopia management. The aim of this review is to interpret the available data to inform clinical practice. We conducted a narrative review of the literature and identified peer-reviewed randomised controlled trials using the search terms 'myopia' and 'atropine', limited to the English language. We identified two key studies, which were the Atropine in the Treatment Of Myopia (ATOM) and Low-concentration Atropine for Myopia Progression (LAMP). Further studies were identified using the above search terms and the references from the identified literature. Atropine 0.01% has a modest effect on controlling axial length progression. Atropine 0.05% appears to be superior to atropine 0.01% in managing myopia progression. There is a dose-dependent rebound effect when treatment is stopped. Atropine is a well-tolerated, safe, and effective intervention. Treatment would be needed for several years and into adolescence, until axial length progression is stable.

The underestimated role of myopia in uncorrectable visual impairment in the United States.

We estimate the US prevalence of uncorrectable visual impairment in 2050 accounting for the changing distribution of both age and myopia. Age projections of the US population (from an estimated total of 379 million in 2050), were taken from the US census website. The distribution of myopia, by severity, was calculated from literature-derived prevalence estimates of 58.4% (≤ - 0.50 D, 2050 projection) and 33.1% (≤ - 1.00 D, 1999-2004 estimate) to provide predicted and conservative estimates, respectively. Uncorrectable visual impairment as a function of age and refractive error was modelled by multiple linear regression. Finally, the likely number of individuals in the US with visual impairment in 2050 was calculated. For a projected myopia prevalence of 58.4%, 222 million are projected to be myopic and 48 million will have high myopia (- 5 D or worse). The projected total number with uncorrectable visual impairment is 11.4 million of which 4.9 million cases (43%) of visual impairment will be directly attributed to increased risk of eye disease associated with myopia. For a projected myopia prevalence of 33.1%, 8.9 million are projected to have uncorrectable visual impairment of which 2.4 million cases (27%) will be directly attributed to myopia. It is predicted that between 27 and 43% of uncorrectable visual impairment in the US population in 2050 will be directly attributable to myopia. Failure to account for the increasing prevalence of myopia among the aging population leads to a substantial underestimate of the prevalence of visual impairment.

Efficacy of the Euclid orthokeratology lens in slowing axial elongation.

PURPOSE: The Euclid Emerald lens designs for orthokeratology have been available in global markets for over 20 years and is used extensively by clinicians for slowing myopia progression in children. This paper comprehensively reviews data from published studies of the efficacy of this lens. METHODS: A comprehensive systematic search was performed in March 2023 using Medline with the following search terms: orthokeratology AND myopi* AND (axial or elong*) NOT (review or meta). RESULTS: The original search identified 189 articles, of which 140 reported axial elongation. Of those, 49 reported data on the Euclid Emerald design. Unique axial elongation data could be extracted from 37 papers-14 of which included an untreated control group. Among these, the mean 12-month efficacy-the difference in axial elongation between orthokeratology wearers and controls-was 0.18 mm (range: 0.05-0.29 mm), and the mean 24-month efficacy was 0.28 mm (range: 0.17-0.38 mm). The orthokeratology wearers in 23 studies without an untreated comparison group showed similar axial elongation to those in the 14 studies with a control group. For example, the mean 12-month axial elongation for the studies with controls was 0.20 ± 0.06 mm compared with 0.20 ± 0.07 mm for the studies without controls. CONCLUSIONS: This extensive body of literature on a single device for myopia control is unique and demonstrates the efficacy of this design in slowing axial elongation in myopic children.

IMI 2023 Digest.

Myopia is a dynamic and rapidly moving field, with ongoing research providing a better understanding of the etiology leading to novel myopia control strategies. In 2019, the International Myopia Institute (IMI) assembled and published a series of white papers across relevant topics and updated the evidence with a digest in 2021. Here, we summarize findings across key topics from the previous 2 years. Studies in animal models have continued to explore how wavelength and intensity of light influence eye growth and have examined new pharmacologic agents and scleral cross-linking as potential strategies for slowing myopia. In children, the term premyopia is gaining interest with increased attention to early implementation of myopia control. Most studies use the IMI definitions of ≤-0.5 diopters (D) for myopia and ≤-6.0 D for high myopia, although categorization and definitions for structural consequences of high myopia remain an issue. Clinical trials have demonstrated that newer spectacle lens designs incorporating multiple segments, lenslets, or diffusion optics exhibit good efficacy. Clinical considerations and factors influencing efficacy for soft multifocal contact lenses and orthokeratology are discussed. Topical atropine remains the only widely accessible pharmacologic treatment. Rebound observed with higher concentration of atropine is not evident with lower concentrations or optical interventions. Overall, myopia control treatments show little adverse effect on visual function and appear generally safe, with longer wear times and combination therapies maximizing outcomes. An emerging category of light-based therapies for children requires comprehensive safety data to enable risk versus benefit analysis. Given the success of myopia control strategies, the ethics of including a control arm in clinical trials is heavily debated. IMI recommendations for clinical trial protocols are discussed.

IMI-Onset and Progression of Myopia in Young Adults.

Myopia typically starts and progresses during childhood, but onset and progression can occur during adulthood. The goals of this review are to summarize published data on myopia onset and progression in young adults, aged 18 to 40 years, to characterize myopia in this age group, to assess what is currently known, and to highlight the gaps in the current understanding. Specifically, the peer-reviewed literature was reviewed to: characterize the timeline and age of stabilization of juvenile-onset myopia; estimate the frequency of adult-onset myopia; evaluate the rate of myopia progression in adults, regardless of age of onset, both during the college years and later; describe the rate of axial elongation in myopic adults; identify risk factors for adult onset and progression; report myopia progression and axial elongation in adults who have undergone refractive surgery; and discuss myopia management and research study design. Adult-onset myopia is common, representing a third or more of all myopia in western populations, but less in East Asia, where onset during childhood is high. Clinically meaningful myopia progression continues in early adulthood and may average 1.00 diopters (D) between 20 and 30 years. Higher levels of myopia are associated with greater absolute risk of myopia-related ocular disease and visual impairment, and thus myopia in this age group requires ongoing management. Modalities established for myopia control in children would be options for adults, but it is difficult to predict their efficacy. The feasibility of studies of myopia control in adults is limited by the long duration required.

Compounded 0.01% Atropine-What's in the Bottle?

OBJECTIVE: To describe the labeling, packaging practices, and characteristics of compounded 0.01% ophthalmic atropine. METHODS: A convenience sample of parents of children who had previously been prescribed low-concentration atropine for myopia management were randomized to obtain 0.01% atropine ophthalmic solution from one of nine compounding pharmacies. The products were analyzed for various important quality attributes. The main outcomes were labeling practices, concentration of atropine and degradant product tropic acid, pH, osmolarity, viscosity, and excipients in 0.01% atropine samples obtained from nine US compounding pharmacies. RESULTS: Twenty-four samples from nine pharmacies were analyzed. The median bottle size was 10 mL (range 3.5-15 mL), and eight of nine pharmacies used clear plastic bottles. Storage recommendations varied and were evenly split between refrigeration (33%), room temperature (33%), and cool, dark, dry location (33%). Beyond use dates ranged from 7 to 175 days (median, 91 days). Median pH of samples was 7.1 (range, 5.5-7.8). Median measured concentration relative to the prescribed concentration was 93.3% (70.4%-104.1%). One quarter of samples were under the 90% minimum target concentration of 0.01%. CONCLUSIONS: An inconsistent and wide variety of formulation and labeling practices exist for compounding 0.01% atropine prescribed to slow pediatric myopia progression.

The future of clinical trials of myopia control.

In the field of myopia control, effective optical or pharmaceutical therapies are now available to patients in many markets. This creates challenges for the conduct of placebo-controlled, randomised clinical trials, including ethics, recruitment, retention, selective loss of faster progressors and non-protocol treatments: Ethics: It is valid to question whether withholding treatment in control subjects is ethical. Recruitment: Availability of treatments is making recruitment into clinical trials more difficult. Retention: If masking is not possible, parents may immediately withdraw their child if randomised to no treatment. Selective loss: Withdrawal of fast progressors in the control group leading to a control group biased towards low progression. Non-protocol treatment: Parents may access other myopia treatments in addition to those within the trial. We propose that future trials may adopt one of the following designs: Non-inferiority trials using an approved drug or device as the control. The choice will depend on whether a regulatory agency has approved the drug or device. Short conventional efficacy trials where data are subsequently entered into a model created from previous clinical trials, which allows robust prediction of long-term treatment efficacy from the initial efficacy. Virtual control group trials based on data relating to axial elongation, myopia progression or both, accounting for subject's age and race. Short-term control data from a cohort, for example, 1 year or less, and applying an appropriate, proportional annual reduction in axial elongation to that population and extrapolating to subsequent years. Time-to-treatment-failure trials using survival analysis; once a treated or control subject progresses or elongates by a given amount, they exit the study and can be offered treatment. In summary, the future development of new treatments in myopia control will be hampered if significant changes are not made to the design of clinical trials in this area.

Incidence of Corneal Adverse Events in Children Wearing Soft Contact Lenses.

OBJECTIVES: There is increasing interest in fitting children with soft contact lenses, in part due to the increase in prescribing of designs to slow the progression of myopia. This literature review summarizes large prospective and retrospective studies that include data on the incidence of microbial keratitis and corneal infiltrative events (CIEs) in children wearing soft contact lenses. METHODS: Peer-reviewed prospective and retrospective studies that report contact lens-related complications in children with at least one year of wear and at least 100 patient years of wear were identified. RESULTS: Seven prospective studies published between 2004 and 2022 were identified representing 3,752 patient years of wear in 1,756 children, nearly all of whom were fitted at age 12 years or younger. Collectively, they report one case of microbial keratitis and 53 CIEs, of which 16 were classified as symptomatic. The overall incidence of microbial keratitis was 2.7 per 10,000 patient years (95% CI: 0.5-15), and the incidence of symptomatic CIEs was 42 per 10,000 patient years (95% CI: 26-69). Two retrospective studies were identified representing 2,545 patient years of wear in 1,025 children, fitted at age 12 years or younger. One study reports two cases of microbial keratitis giving an incidence of 9.4 per 10,000 patient years (95% CI: 0.5-15). CONCLUSIONS: Accurate classification of CIEs is challenging, particularly in retrospective studies. The incidence of microbial keratitis in children wearing soft lenses is no higher than in adults, and the incidence of CIEs seems to be markedly lower.

Epidemiology and Burden of Astigmatism: A Systematic Literature Review.

SIGNIFICANCE: This is the first literature review to report the epidemiology, patient burden, and economic burden of astigmatism in the general adult population. The unmet needs of astigmatism patients with coexisting ocular conditions (cataract, glaucoma, dry eye, presbyopia, or macular degeneration) and risks associated with untreated astigmatism are also reviewed and reported. PURPOSE: This study aimed to identify, report, and summarize the published literature on epidemiology, patient burden, and economic burden of astigmatism using a systematic literature review. METHODS: MEDLINE, EMBASE, and Cochrane Library databases were searched (January 1996 to May 2021). Search results were limited to the English language. Proceedings (2018 to 2021) from ophthalmology congresses were searched along with gray literature using the Google Scholar platform. RESULTS: The literature search yielded 6804 citations, of which 125 met the inclusion criteria (epidemiology, 68; patient burden, 60; economic burden, 6). Astigmatism prevalence in the general population varied from 8 to 62%, with higher rates in individuals 70 years or older. The prevalence of with-the-rule astigmatism was higher in individuals 40 years or younger, whereas rates of against-the-rule and oblique astigmatism increased with age. Astigmatic patients experienced decreased vision quality, increased glare (53 to 77%), haloes (28 to 80%), night-time driving difficulties (66%), falls, and spectacle dependence (45 to 85%). Astigmatic patients performed vision-related tasks slower (1 D, 9% slower; 2 D, 29% slower) and made more errors (1 D, 38% more errors; 2 D, 370% more errors) compared with fully corrected individuals. In cataract patients with astigmatism, the annual mean per-patient productivity loss costs ranged from €55 ($71) to €84 ($108), and mean informal care costs ranged from €30 ($39) to €55 ($71) with a mean of 2.3 to 4.1 hours spent on informal care. CONCLUSIONS: Uncorrected astigmatism decreases patients' vision-related quality of life, decreases productivity among working-age adults, and poses an economic burden on patients and their families.