Predicting the onset of myopia in children by age, sex, and ethnicity: Results from the CLEERE Study.

SIGNIFICANCE: Clinicians and researchers would benefit from being able to predict the onset of myopia for an individual child. This report provides a model for calculating the probability of myopia onset, year-by-year and cumulatively, based on results from the largest, most ethnically diverse study of myopia onset in the United States. PURPOSE: This study aimed to model the probability of the onset of myopia in previously nonmyopic school-aged children. METHODS: Children aged 6 years to less than 14 years of age at baseline participating in the Collaborative Longitudinal Evaluation of Ethnicity and Refractive Error (CLEERE) Study who were nonmyopic and less hyperopic than +3.00 D (spherical equivalent) were followed up for 1 to 7 years through eighth grade. Annual measurements included cycloplegic autorefraction, keratometry, ultrasound axial dimensions, and parental report of children's near work and time spent in outdoor and/or sports activities. The onset of myopia was defined as the first visit with at least -0.75 D of myopia in each principal meridian. The predictive model was built using discrete time survival analysis and evaluated with C statistics. RESULTS: The model of the probability of the onset of myopia included cycloplegic spherical equivalent refractive error, the horizontal/vertical component of astigmatism (J0), age, sex, and race/ethnicity. Onset of myopia was more likely with lower amounts of hyperopia and less positive/more negative values of J0. Younger Asian American females had the highest eventual probability of onset, whereas older White males had the lowest. Model performance increased with older baseline age, with C statistics ranging from 0.83 at 6 years of age to 0.92 at 13 years. CONCLUSIONS: The probability of the onset of myopia can be estimated for children in the major racial/ethnic groups within the United States on a year-by-year and cumulative basis up to age 14 years based on a simple set of refractive error and demographic variables.

Talkin' 'bout my(opia) generation: The impact of Optometry and Vision Science.

VIRTUAL ISSUE EDITORIAL: This editorial fronts the first virtual issue for Optometry & Vision Science. Virtual issues are a collection of papers from previously published issues of the journal that are brought together in a single, online publication. They highlight the important contribution the journal has made in supporting myopia research. All the papers referenced and previously published in Optometry & Vision Science will be made free access for 1-month. The collection can be accessed here: https://journals.lww.com/optvissci/pages/collectiondetails.aspx?TopicalCollectionId=16.

Evaluation of Rinsing Options for Rigid Gas Permeable Contact Lenses.

OBJECTIVES: This study assessed the efficacy of various saline solutions as alternative methods to rinsing rigid gas permeable (RGP) lenses with tap water. METHODS: The exiting fluid pressure of five commercially available saline solutions was measured using a venous pressure transducer system. Rigid gas permeable lenses were cleaned with one of two commercially available cleaners and then rinsed with one of five saline solutions or with tap water. High-resolution imaging was performed after each rinse, and light transmission through the lens surface was determined by measuring the mean pixel count within a 1 mm by 1 mm square. RESULTS: The mean pixels/mm 2 and the rinsing method were correlated (Spearman rank order correlation, P <0.0001), that is, high pixel counts represented more lens surface deposits and residue, and as fluid pressure of the rinsing methods increased, mean pixels/mm 2 decreased. CONCLUSIONS: Measured fluid pressure relates to lens surface opacity suggesting that some products leave less residue than others. In addition, tap water, with its high exiting fluid pressure, seems to be the most effective option for removal of RGP cleaners from the contact lens surface. Despite these findings, tap water rinse is not encouraged because of its potential to lead to corneal inflammation and infection; therefore, the development of alternative procedures and products is needed.

Efficacy and Safety of 0.01% and 0.02% Atropine for the Treatment of Pediatric Myopia Progression Over 3 Years: A Randomized Clinical Trial.

Importance: The global prevalence of myopia is predicted to approach 50% by 2050, increasing the risk of visual impairment later in life. No pharmacologic therapy is approved for treating childhood myopia progression. Objective: To assess the safety and efficacy of NVK002 (Vyluma), a novel, preservative-free, 0.01% and 0.02% low-dose atropine formulation for treating myopia progression. Design, Setting, and Participants: This was a double-masked, placebo-controlled, parallel-group, randomized phase 3 clinical trial conducted from November 20, 2017, through August 22, 2022, of placebo vs low-dose atropine, 0.01% and 0.02% (2:2:3 ratio). Participants were recruited from 26 clinical sites in North America and 5 countries in Europe. Enrolled participants were 3 to 16 years of age with -0.50 diopter (D) to -6.00 D spherical equivalent refractive error (SER) and no worse than -1.50 D astigmatism. Interventions: Once-daily placebo, low-dose atropine, 0.01%, or low-dose atropine, 0.02%, eye drops for 36 months. Main Outcomes and Measures: The primary, prespecified end point was the proportion of participants' eyes responding to 0.02% atropine vs placebo therapy (<0.50 D myopia progression at 36 months [responder analysis]). Secondary efficacy end points included responder analysis for atropine, 0.01%, and mean change from baseline in SER and axial length at month 36 in a modified intention-to-treat population (mITT; participants 6-10 years of age at baseline). Safety measurements for treated participants (3-16 years of age) were reported. Results: A total of 576 participants were randomly assigned to treatment groups. Of these, 573 participants (99.5%; mean [SD] age, 8.9 [2.0] years; 315 female [54.7%]) received trial treatment (3 participants who were randomized did not receive trial drug) and were included in the safety set. The 489 participants (84.9%) who were 6 to 10 years of age at randomization composed the mITT set. At month 36, compared with placebo, low-dose atropine, 0.02%, did not significantly increase the responder proportion (odds ratio [OR], 1.77; 95% CI, 0.50-6.26; P = .37) or slow mean SER progression (least squares mean [LSM] difference, 0.10 D; 95% CI, -0.02 D to 0.22 D; P = .10) but did slow mean axial elongation (LSM difference, -0.08 mm; 95% CI, -0.13 mm to -0.02 mm; P = .005); however, at month 36, compared with placebo, low-dose atropine, 0.01%, significantly increased the responder proportion (OR, 4.54; 95% CI, 1.15-17.97; P = .03), slowed mean SER progression (LSM difference, 0.24 D; 95% CI, 0.11 D-0.37 D; P < .001), and slowed axial elongation (LSM difference, -0.13 mm; 95% CI, -0.19 mm to -0.07 mm; P < .001). There were no serious ocular adverse events and few serious nonocular events; none was judged as associated with atropine. Conclusions and Relevance: This randomized clinical trial found that 0.02% atropine did not significantly increase the proportion of participants' eyes responding to therapy but suggested efficacy for 0.01% atropine across all 3 main end points compared with placebo. The efficacy and safety observed suggest that low-dose atropine may provide a treatment option for childhood myopia progression. Trial Registration: ClinicalTrials.gov Identifier: NCT03350620.

2020 Charles F. Prentice Lecture: I Can See Clearly Now.

ABSTRACT: The Charles F. Prentice Medal, which was first given the year I was born, is the highest research honor bestowed by the American Academy of Optometry. I received the Prentice Medal in 2020 and gave my presentation at the 2020 American Academy of Optometry meeting, which was entirely virtual. As the first female optometrist to receive the Prentice Medal, I am honored to be given the opportunity to provide this summary of my presentation.Myopia treatment choices to slow the progression of juvenile-onset myopia, especially in the first year of treatment, range from spectacles to contact lenses to pharmaceuticals. The value of the work described here that aims to predict the onset of myopia in children based on measurements that could be made by the optometrist is about to become more relevant than ever. What if the age-specific cutpoints could be used to use a low-risk treatment that would actually prevent the development of myopia altogether?

Compensation for Vitreous Chamber Elongation in Infancy and Childhood.

SIGNIFICANCE: The ratios of diopters of change in refractive error produced per millimeter of eye elongation (D/mm) are rarely those predicted from geometric optics because of changes in other ocular components. Quantifying this optical compensation in millimeters instead of ratios reveals some important principles about eye growth and refractive error. PURPOSE: The study purpose was to sort total vitreous chamber elongation into millimeters that either contributed (uncompensated) or did not contribute to change in refractive error (compensated). METHODS: Participants were infants in the Berkeley Infant Biometry Study (n = 271, ages 3 months to 6 years) or schoolchildren in the Collaborative Longitudinal Evaluation of Ethnicity and Refractive Error (n = 456 emmetropes and 522 myopes, ages 6 to 14 years). Refractive error was measured using cycloplegic retinoscopy in infants (cyclopentolate 1%) and cycloplegic autorefraction in schoolchildren (tropicamide 1% or combined with cyclopentolate 1%). Axial dimensions were assessed using A-scan ultrasonography. Uncompensated millimeters were estimated from ratios of change in refractive error per millimeter of elongation using Gullstrand eye models. Compensated millimeters were the difference between measured elongation and uncompensated millimeters. RESULTS: Compensated millimeters exceeded uncompensated millimeters in emmetropic children across ages, but uncompensated millimeters exceeded compensated millimeters in myopic children. Compensated millimeters were highest in infancy and decreased with age, reaching less than 0.10 mm per year by age 10 years in both myopic and emmetropic children. There were no statistically significant differences in compensated millimeters between myopic and emmetropic children between ages 8 and 14 years ( P values from .17 to .73). CONCLUSIONS: The ability of the ocular components, primarily crystalline lens, to compensate for vitreous elongation is independent of the higher demands of myopic eye growth. The limited compensation after age 10 years suggests the target for elongation in myopia control needed to arrest myopia progression may be that seen in emmetropes or less.

The Limited Value of Prior Change in Predicting Future Progression of Juvenile-onset Myopia.

SIGNIFICANCE: Identifying children at highest risk for rapid myopia progression and/or rapid axial elongation could help prioritize who should receive clinical treatment or be enrolled in randomized clinical trials. Our models suggest that these goals are difficult to accomplish. PURPOSE: This study aimed to develop models predicting future refractive error and axial length using children's baseline data and history of myopia progression and axial elongation. METHODS: Models predicting refractive error and axial length were created using randomly assigned training and test data sets from 916 myopic participants in the Collaborative Longitudinal Evaluation of Ethnicity and Refractive Error Study. Subjects were 7 to 14 years of age at study entry with three consecutive annual visits that included cycloplegic A-scan ultrasound and autorefraction. The effect of adding prior change in axial length and refractive error was evaluated for each model. RESULTS: Age, ethnicity, and greater myopia were significant predictors of future refractive error and axial length, whereas prior progression or elongation, near work, time outdoors, and parental myopia were not. The 95% limits for the difference between actual and predicted change were ±0.22 D and ±0.14 mm without prior change data compared with ±0.26 D and ±0.16 mm with prior change data. Sensitivity and specificity for identifying fast progressors were between 60.8 and 63.2%, respectively, when the cut points were close to the sample average. Positive predictive value and sample yield were even lower when the cut points were more extreme. CONCLUSIONS: Young, more myopic Asian American children in the Collaborative Longitudinal Evaluation of Ethnicity and Refractive Error Study were the most likely to progress rapidly. Clinical trials should expect average progression rates that reflect sample demographics and may have difficulty recruiting generalizable samples that progress faster than that average. Knowing progression or elongation history does not seem to help the clinical decision regarding initiating myopia control.

Myopia Progression as a Function of Sex, Age, and Ethnicity.

Purpose: To model juvenile-onset myopia progression as a function of race/ethnicity, age, sex, parental history of myopia, and time spent reading or in outdoor/sports activity. Methods: Subjects were 594 children in the Collaborative Longitudinal Evaluation of Ethnicity and Refractive Error (CLEERE) Study with at least three study visits: one visit with a spherical equivalent (SPHEQ) less myopic/more hyperopic than -0.75 diopter (D), the first visit with a SPHEQ of -0.75 D or more myopia (onset visit), and another after myopia onset. Myopia progression from the time of onset was modeled using cubic models as a function of age, race/ethnicity, and other covariates. Results: Younger children had faster progression of myopia; for example, the model-estimated 3-year progression in an Asian American child was -1.93 D when onset was at age 7 years compared with -1.43 D when onset was at age 10 years. Annual progression for girls was 0.093 D faster than for boys. Asian American children experienced statistically significantly faster myopia progression compared with Hispanic (estimated 3-year difference of -0.46 D), Black children (-0.88 D), and Native American children (-0.48 D), but with similar progression compared with White children (-0.19 D). Parental history of myopia, time spent reading, and time spent in outdoor/sports activity were not statistically significant factors in multivariate models. Conclusions: Younger age, female sex, and racial/ethnic group were the factors associated with faster myopic progression. This multivariate model can facilitate the planning of clinical trials for myopia control interventions by informing the prediction of myopia progression rates.

Predicting the onset of myopia in children: results from the CLEERE study.

Research often attempts to identify risk factors associated with prevalent disease or that change the probability of developing disease. These factors may also help in predicting which individuals may go on to develop the condition of interest. However, risk factors may not always serve as the best predictive factors and not all predictive factors should be considered as risk factors. A child's current refractive error, parental history of myopia, and the amount of time children spend outdoors are excellent examples. Parental myopia and time outdoors are meaningful risk factors because they alter the probability of developing myopia and point to important hereditary and environmental influences. A child's current refractive error points to no particular mechanism and is therefore a poor risk factor. However, it serves as an excellent predictive factor for identifying children likely to develop future myopia. Risk factors may explain how a child reached a particular level of refractive error, but knowledge of that history may not be needed in order to make an accurate prediction about future refractive error. Current refractive error alone may be sufficient. This difference between risk factors and predictive factors is not always appreciated in the literature, including a recent publication in BMC Ophthalmology. This letter attempts to make that distinction and to explain why parental myopia and time outdoors are significant risk factors in the Collaborative Longitudinal Evaluation of Ethnicity and Refractive Error, yet are not significant for predicting future myopia in a multivariate model that contains current refractive error.

Uncorrected Refractive Error and Distance Visual Acuity in Children Aged 6 to 14 Years.

SIGNIFICANCE: This study presents the relationship between distance visual acuity and a range of uncorrected refractive errors, a complex association that is fundamental to clinical eye care and the identification of children needing refractive correction. PURPOSE: This study aimed to analyze data from the Collaborative Longitudinal Evaluation of Ethnicity and Refractive Error Study to describe the relationship between distance uncorrected refractive error and visual acuity in children. METHODS: Subjects were 2212 children (51.2% female) 6 to 14 years of age (mean ± standard deviation, 10.2 ± 2.1 years) participating in the Collaborative Longitudinal Evaluation of Ethnicity and Refractive Error Study between 2000 and 2010. Uncorrected distance visual acuity was measured using a high-contrast projected logMAR chart. Cycloplegic refractive error was measured using the Grand Seiko WR-5100K autorefractor. The ability of logMAR acuity to detect various categories of refractive error was examined using receiver operating characteristic curves. RESULTS: Isoacuity curves show that increasing myopic spherical refractive errors, increasing astigmatic refractive errors, or a combination of both reduces distance visual acuity. Visual acuity was reduced by approximately 0.5 minutes of MAR per 0.30 to 0.40 D of spherical refractive error and by approximately 0.5 minutes of MAR per 0.60 to 0.90 D of astigmatism. Higher uncorrected hyperopic refractive error had little effect on distance visual acuity. Receiver operating characteristic curve analysis suggests that a logMAR distance acuity of 0.20 to 0.32 provides the best balance between sensitivity and specificity for detecting refractive errors other than hyperopia. Distance acuity alone was ineffective for detecting hyperopic refractive errors. CONCLUSIONS: Higher myopic and/or astigmatic refractive errors were associated with predictable reductions in uncorrected distance visual acuity. The reduction in acuity per diopter of cylindrical error was about half that for spherical myopic error. Although distance acuity may be a useful adjunct to the detection of myopic spherocylindrical refractive errors, accommodation presumably prevents acuity from assisting in the detection of hyperopia. Alternate procedures need to be used to detect hyperopia.

An Analysis of the Optometric Applicant Pool Relative to Matriculants.

SIGNIFICANCE: The interplay of applicants to optometry school and matriculants has not been explored systematically. It is vital that the profession examines these trends to ensure a viable pipeline of future doctors of optometry. PURPOSE: The purpose of this study was to describe the demographics and academic qualifications of entering optometry classes from autumn 2010 through autumn 2018 of U.S.-based optometric institutions' application pool and matriculants (enrollees). METHODS: Data were gathered from reports generated from accredited schools and colleges of optometry in the United States and compiled by the Association of Schools and Colleges of Optometry (publicly available) and the Optometry Centralized Application Service. Metrics included the annual number of verified applicants, the annual number of matriculants, the home region of U.S.-based applicants, and the Optometry Admission Test (OAT) performance and grade point average of verified applicants. RESULTS: The number of verified applicants for autumn 2018 was 0.95% higher than that for autumn 2010, yet the number of matriculants in 2018 compared with 2010 increased by 11.2% with an applicant-to-matriculant ratio in 2010 of 1.53 compared with 1.39 in 2018. Grade point average and academic average OAT scores were stable from 2010 to 2018. The ratios of verified applicants with an academic average OAT score of at least 300 to matriculants were 0.87 for autumn 2018 and 0.92 for autumn 2010. The ratios of verified applicants with a grade point average of at least 3.00 to matriculants were 1.13 for autumn 2018 and 1.23 for autumn 2015. CONCLUSIONS: Evidence supports the conclusion that the applicant pool has remained essentially flat for the last decade, whereas the number of matriculants has increased substantially; thus, the number of qualified applicants to matriculants has logically decreased. In the last 2 years, optometric programs have responded by decreasing their institution's number of matriculants to accommodate the national trends.

Intrastromal corneal ring segments for treating keratoconus.

BACKGROUND: Keratoconus is a degenerative condition of the cornea that profoundly affects vision and vision-specific quality of life. The axial cornea thins and protrudes, resulting in irregularity and, eventually, scarring of the cornea. There are multiple options available for treating keratoconus. Intrastromal corneal ring segments are small, crescent-shaped plastic rings that are placed in the deep, peripheral corneal stroma in order to flatten the cornea. They are made of polymethylmethacrylate (PMMA). The procedure does not involve corneal tissue nor does it invade the central optical zone. Intrastromal corneal ring segments are approved for use when contact lenses or spectacles are no longer adequate. OBJECTIVES: To evaluate the effectiveness and safety of intrastromal corneal ring segments as a treatment for keratoconus. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (2018, Issue 1); Ovid MEDLINE; Embase.com; PubMed; Latin American and Caribbean Health Sciences Literature Database (LILACS); ClinicalTrials.gov and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP). We did not implement any date or language restrictions in the electronic search for trials. We last searched the electronic databases on 25 January 2018. SELECTION CRITERIA: Two review authors independently assessed records from the electronic searches to identify randomized controlled trials (RCTs). Disagreements were resolved by discussion. DATA COLLECTION AND ANALYSIS: We planned for two authors to independently review full-text reports, using standard methodological procedures expected by Cochrane. MAIN RESULTS: We found no RCTs comparing intrastromal corneal ring segments with spectacles or contact lenses. AUTHORS' CONCLUSIONS: In the absence of eligible RCTs to review, no conclusions can be drawn.

The Response AC/A Ratio Before and After the Onset of Myopia.

Purpose: To investigate the ratio of accommodative convergence per diopter of accommodative response (AC/A ratio) before, during, and after myopia onset. Methods: Subjects were 698 children aged 6 to 14 years who became myopic and 430 emmetropic children participating in the Collaborative Longitudinal Evaluation of Ethnicity and Refractive Error. Refractive error was measured using cycloplegic autorefraction, near work by parent survey, and the AC/A ratio by simultaneously monitoring convergence and accommodative response. The response AC/A ratios of children who became myopic were compared with age-, sex-, and ethnicity-matched model estimates for emmetropic children from 5 years before through 5 years after the onset of myopia. Results: The response AC/A ratio was not significantly different between the two groups 5 years before onset, then increased monotonically in children who became myopic until reaching a plateau at myopia onset of about 7 Δ/D compared to about 4 Δ/D for children who remained emmetropic (differences between groups significant at P < 0.01 from 4 years before onset through 5 years after onset). A higher AC/A ratio was associated with greater accommodative lag but not with the rate of myopia progression regardless of the level of near work. Conclusions: An increasing AC/A ratio is an early sign of becoming myopic, is related to greater accommodative lag, but does not affect the rate of myopia progression. The association with accommodative lag suggests that the AC/A ratio increase is from greater neural effort needed per diopter of accommodation rather than change in the accommodative convergence crosslink gain relationship.

The Effect of Age, Accommodation, and Refractive Error on the Adult Human Eye.

PURPOSE: To quantify changes in ocular dimensions associated with age, refractive error, and accommodative response, in vivo, in 30- to 50-year-old human subjects. METHODS: The right eyes of 91 adults were examined using ultrasonography, phakometry, keratometry, pachymetry, interferometry, anterior segment optical coherence tomography, and high-resolution magnetic resonance imaging. Accommodation was measured subjectively with a push-up test and objectively using open-field autorefraction. Regression analyses were used to assess differences in ocular parameters with age, refractive error, and accommodation. RESULTS: With age, crystalline lens thickness increased (0.03 mm/yr), anterior lens curvature steepened (0.11 mm/yr), anterior chamber depth decreased (0.02 mm/yr), and lens equivalent refractive index decreased (0.001/yr) (all p < 0.01). With increasing myopia, there were significant increases in axial length (0.37 mm/D), vitreous chamber depth (0.34 mm/D), vitreous chamber height (0.09 mm/D), and ciliary muscle ring diameter (0.10 mm/D) (all p < 0.05). Increasing myopia was also associated with steepening of both the cornea (0.16 mm/D) and anterior lens surface (0.011 mm/D) (both p < 0.04). With accommodation, the ciliary muscle ring diameter decreased (0.08 mm/D) and the muscle thinned posteriorly (0.008 mm/D), allowing the lens to shorten equatorially (0.07 mm/D) and thicken axially (0.06 mm/D) (all p < 0.03). CONCLUSIONS: Refractive error is significantly correlated with not only the axial dimensions but also the anterior equatorial dimension of the adult eye. Further testing and development of accommodating intraocular lenses should account for differences in patients' preoperative refractive error.

Who Says There's Nothing New under the Sun?

The time since our first publication in 2007 describing time spent outdoors as protective for juvenile myopia onset to clinical trials incorporating outdoor light interventions has been short. The time outdoors/myopia example highlights the incorporation of clinical or epidemiologic evidence to translational research that may eventually change clinical practice and/or behavior.

Prediction of Juvenile-Onset Myopia.

IMPORTANCE: Myopia (nearsightedness) has its onset in childhood and affects about one-third of adults in the United States. Along with its high prevalence, myopia is expensive to correct and is associated with ocular diseases that include glaucoma and retinal detachment. OBJECTIVE: To determine the best set of predictors for myopia onset in school-aged children. DESIGN, SETTING, AND PARTICIPANTS: The Collaborative Longitudinal Evaluation of Ethnicity and Refractive Error (CLEERE) Study was an observational cohort study of ocular development and myopia onset conducted at 5 clinical sites from September 1, 1989, through May 22, 2010. Data were collected from 4512 ethnically diverse, nonmyopic school-aged children from grades 1 through 8 (baseline grades 1 through 6) (ages 6 through 13 years [baseline, 6 through 11 years]). MAIN OUTCOMES AND MEASURES: We evaluated 13 candidate risk factors for their ability to predict the onset of myopia. Myopia onset was defined as -0.75 diopters or more of myopia in each principal meridian in the right eye as measured by cycloplegic autorefraction at any visit after baseline until grade 8 (age 13 years). We evaluated risk factors using odds ratios from discrete time survival analysis, the area under the curve, and cross validation. RESULTS: A total of 414 children became myopic from grades 2 through 8 (ages 7 through 13 years). Of the 13 factors evaluated, 10 were associated with the risk for myopia onset (P < .05). Of these 10 factors, 8 retained their association in multivariate models: spherical equivalent refractive error at baseline, parental myopia, axial length, corneal power, crystalline lens power, ratio of accommodative convergence to accommodation (AC/A ratio), horizontal/vertical astigmatism magnitude, and visual activity. A less hyperopic/more myopic baseline refractive error was consistently associated with risk of myopia onset in multivariate models (odds ratios from 0.02 to 0.13, P < .001), while near work, time outdoors, and having myopic parents were not. Spherical equivalent refractive error was the single best predictive factor that performed as well as all 8 factors together, with an area under the curve (C statistic) ranging from 0.87 to 0.93 (95% CI, 0.79-0.99). CONCLUSIONS AND RELEVANCE: Future myopia can be predicted in a nonmyopic child using a simple, single measure of refractive error. Future trials for prevention of myopia should target the child with low hyperopia as the child at risk.