Peripheral Defocus, Pupil Size, and Axial Eye Growth in Children Wearing Soft Multifocal Contact Lenses in the BLINK Study.

Purpose: The purpose of this study was to evaluate the relationship between peripheral defocus and pupil size on axial growth in children randomly assigned to wear either single vision contact lenses, +1.50 diopter (D), or +2.50 D addition multifocal contact lenses (MFCLs). Methods: Children 7 to 11 years old with myopia (-0.75 to -5.00 D; spherical component) and ≤1.00 D astigmatism were enrolled. Autorefraction (horizontal meridian; right eye) was measured annually wearing contact lenses centrally and ±20 degrees, ±30 degrees, and ±40 degrees from the line of sight at near and distance. Photopic and mesopic pupil size were measured. The effects of peripheral defocus, treatment group, and pupil size on the 3-year change in axial length were modeled using multiple variables that evaluated defocus across the retina. Results: Although several peripheral defocus variables were associated with slower axial growth with MFCLs, they were either no longer significant or not meaningfully associated with eye growth after the treatment group was included in the model. The treatment group assignment better explained the slower eye growth with +2.50 MFCLs than peripheral defocus. Photopic and mesopic pupil size did not modify eye growth with the +2.50 MFCL (all P ≥ 0.37). Conclusions: The optical signal causing slower axial elongation with +2.50 MFCLs is better explained by the lens type worn than by peripheral defocus. The signal might be something other than peripheral defocus, or there is not a linear dose-response relationship within treatment groups. We found no evidence to support pupil size as a criterion when deciding which myopic children to treat with MFCLs.

Quality of life after wearing multifocal contact lenses for myopia control for 2 weeks in the BLINK Study.

PURPOSE: To validate Pediatric Refractive Error Profile 2 (PREP2) subscales that can be used to evaluate contact lens wearers and compare vision-specific quality of life measurements between children wearing multifocal and single vision contact lenses for 2 weeks. METHODS: Two hundred and ninety-four myopic children aged 7-11 years (inclusive) were enrolled in the 3-year, double-masked Bifocal Lenses In Nearsighted Kids (BLINK) Study. Participants completed the PREP2 survey after having worn contact lenses for 2 weeks. The Vision, Symptoms, Activities and Overall PREP2 subscales were used to compare participants' subjective assessment while wearing +1.50 or +2.50 D add multifocal or single vision contact lenses. Rasch analysis was used to validate each subscale and to compare participants' subjective assessment of contact lens wear. RESULTS: Item fit to the Rasch model was good for all scales, with no individual items having infit mean square statistics outside the recommended range (0.7-1.3). Response category function was acceptable for all subscales, with ordered category thresholds. Measurement precision, assessed by the Rasch person reliability statistic, was less than ideal (≥0.8) for three of the subscales, but met the minimum acceptable standard of 0.5. Scores for the Vision subscale differed by treatment assignment (p = 0.03), indicating that participants with the highest add power reported statistically worse quality of vision, although the difference was only 3.9 units on a scale of 1-100. Girls reported fewer symptoms than boys (p = 0.006), but there were no other differences between boys and girls. CONCLUSIONS: Rasch analysis demonstrates that the PREP2 survey is a valid instrument for assessing refractive error-specific quality of life. These results suggest that vision-related quality of life is not meaningfully affected by 2 weeks of soft multifocal contact lens wear for myopia control.

Accommodation in Children after 4.7 Years of Multifocal Contact Lens Wear in the BLINK Study Randomized Clinical Trial.

SIGNIFICANCE: When worn for myopia control in children, soft multifocal contact lenses with a +2.50 D add reduced the accommodative response over a 3-year period, but wearing them for more than 4 years did not affect accommodative amplitudes, lag, or facility. PURPOSE: This study aimed to compare the accommodative response to a 3D stimulus between single-vision, +1.50-D add, and +2.50-D add multifocal contact lens wearers during 3 years of contact lens wear and then to compare accommodative amplitude, lag, and facility between the three groups after an average of 4.7 years of wear. METHODS: Bifocal Lenses In Nearsighted Kids study participants aged 7 to 11 years old were randomly assigned to wear single-vision, +1.50-D add, or +2.50-D add soft contact lenses (CooperVision, Pleasanton, CA). The accommodative response to a 3D stimulus was measured at baseline and annually for 3 years. After 4.7 years, we measured objective accommodative amplitudes, lead/lag, and binocular facility with ±2.00-D flippers. We compared the three accommodative measures using multivariate analysis of variance (MANOVA), adjusting for clinic site, sex, and age group (7 to 9 or 10 to 11 years). RESULTS: The +2.50-D add contact lens wearers exhibited lower accommodative response than the single-vision contact lens wearers for 3 years, but the +1.50-D add contact lens wearers exhibited only lower accommodative response than did the single-vision contact lens wearers for 2 years. After adjustment for clinic site, sex, and age group, there were no statistically significant or clinically meaningful differences between the three treatment groups for accommodative amplitude (MANOVA, P = .49), accommodative lag (MANOVA, P = .41), or accommodative facility (MANOVA, P = .87) after an average of 4.7 years of contact lens wear. CONCLUSIONS: Almost 5 years of multifocal contact lens wear did not affect the accommodative amplitude, lag, or facility of children.

Interventions for myopia control in children: a living systematic review and network meta-analysis.

BACKGROUND: Myopia is a common refractive error, where elongation of the eyeball causes distant objects to appear blurred. The increasing prevalence of myopia is a growing global public health problem, in terms of rates of uncorrected refractive error and significantly, an increased risk of visual impairment due to myopia-related ocular morbidity. Since myopia is usually detected in children before 10 years of age and can progress rapidly, interventions to slow its progression need to be delivered in childhood. OBJECTIVES: To assess the comparative efficacy of optical, pharmacological and environmental interventions for slowing myopia progression in children using network meta-analysis (NMA). To generate a relative ranking of myopia control interventions according to their efficacy. To produce a brief economic commentary, summarising the economic evaluations assessing myopia control interventions in children. To maintain the currency of the evidence using a living systematic review approach.  SEARCH METHODS: We searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register), MEDLINE; Embase; and three trials registers. The search date was 26 February 2022.  SELECTION CRITERIA: We included randomised controlled trials (RCTs) of optical, pharmacological and environmental interventions for slowing myopia progression in children aged 18 years or younger. Critical outcomes were progression of myopia (defined as the difference in the change in spherical equivalent refraction (SER, dioptres (D)) and axial length (mm) in the intervention and control groups at one year or longer) and difference in the change in SER and axial length following cessation of treatment ('rebound').  DATA COLLECTION AND ANALYSIS: We followed standard Cochrane methods. We assessed bias using RoB 2 for parallel RCTs. We rated the certainty of evidence using the GRADE approach for the outcomes: change in SER and axial length at one and two years. Most comparisons were with inactive controls. MAIN RESULTS: We included 64 studies that randomised 11,617 children, aged 4 to 18 years. Studies were mostly conducted in China or other Asian countries (39 studies, 60.9%) and North America (13 studies, 20.3%). Fifty-seven studies (89%) compared myopia control interventions (multifocal spectacles, peripheral plus spectacles (PPSL), undercorrected single vision spectacles (SVLs), multifocal soft contact lenses (MFSCL), orthokeratology, rigid gas-permeable contact lenses (RGP); or pharmacological interventions (including high- (HDA), moderate- (MDA) and low-dose (LDA) atropine, pirenzipine or 7-methylxanthine) against an inactive control. Study duration was 12 to 36 months. The overall certainty of the evidence ranged from very low to moderate. Since the networks in the NMA were poorly connected, most estimates versus control were as, or more, imprecise than the corresponding direct estimates. Consequently, we mostly report estimates based on direct (pairwise) comparisons below. At one year, in 38 studies (6525 participants analysed), the median change in SER for controls was -0.65 D. The following interventions may reduce SER progression compared to controls: HDA (mean difference (MD) 0.90 D, 95% confidence interval (CI) 0.62 to 1.18), MDA (MD 0.65 D, 95% CI 0.27 to 1.03), LDA (MD 0.38 D, 95% CI 0.10 to 0.66), pirenzipine (MD 0.32 D, 95% CI 0.15 to 0.49), MFSCL (MD 0.26 D, 95% CI 0.17 to 0.35), PPSLs (MD 0.51 D, 95% CI 0.19 to 0.82), and multifocal spectacles (MD 0.14 D, 95% CI 0.08 to 0.21). By contrast, there was little or no evidence that RGP (MD 0.02 D, 95% CI -0.05 to 0.10), 7-methylxanthine (MD 0.07 D, 95% CI -0.09 to 0.24) or undercorrected SVLs (MD -0.15 D, 95% CI -0.29 to 0.00) reduce progression.  At two years, in 26 studies (4949 participants), the median change in SER for controls was -1.02 D. The following interventions may reduce SER progression compared to controls: HDA (MD 1.26 D, 95% CI 1.17 to 1.36), MDA (MD 0.45 D, 95% CI 0.08 to 0.83), LDA (MD 0.24 D, 95% CI 0.17 to 0.31), pirenzipine (MD 0.41 D, 95% CI 0.13 to 0.69), MFSCL (MD 0.30 D, 95% CI 0.19 to 0.41), and multifocal spectacles  (MD 0.19 D, 95% CI 0.08 to 0.30). PPSLs (MD 0.34 D, 95% CI -0.08 to 0.76) may also reduce progression, but the results were inconsistent. For RGP, one study found a benefit and another found no difference with control. We found no difference in SER change for undercorrected SVLs (MD 0.02 D, 95% CI -0.05 to 0.09). At one year, in 36 studies (6263 participants), the median change in axial length for controls was 0.31 mm. The following interventions may reduce axial elongation compared to controls: HDA (MD -0.33 mm, 95% CI -0.35 to 0.30), MDA (MD -0.28 mm, 95% CI -0.38 to -0.17), LDA (MD -0.13 mm, 95% CI -0.21 to -0.05), orthokeratology (MD -0.19 mm, 95% CI -0.23 to -0.15), MFSCL (MD -0.11 mm, 95% CI -0.13 to -0.09), pirenzipine (MD -0.10 mm, 95% CI -0.18 to -0.02), PPSLs (MD -0.13 mm, 95% CI -0.24 to -0.03), and multifocal spectacles (MD -0.06 mm, 95% CI -0.09 to -0.04). We found little or no evidence that RGP (MD 0.02 mm, 95% CI -0.05 to 0.10), 7-methylxanthine (MD 0.03 mm, 95% CI -0.10 to 0.03) or undercorrected SVLs (MD 0.05 mm, 95% CI -0.01 to 0.11) reduce axial length. At two years, in 21 studies (4169 participants), the median change in axial length for controls was 0.56 mm. The following interventions may reduce axial elongation compared to controls: HDA (MD -0.47mm, 95% CI -0.61 to -0.34), MDA (MD -0.33 mm, 95% CI -0.46 to -0.20), orthokeratology (MD -0.28 mm, (95% CI -0.38 to -0.19), LDA (MD -0.16 mm, 95% CI -0.20 to  -0.12), MFSCL (MD -0.15 mm, 95% CI -0.19 to -0.12), and multifocal spectacles (MD -0.07 mm, 95% CI -0.12 to -0.03). PPSL may reduce progression (MD -0.20 mm, 95% CI -0.45 to 0.05) but results were inconsistent. We found little or no evidence that undercorrected SVLs (MD -0.01 mm, 95% CI -0.06 to 0.03) or RGP (MD 0.03 mm, 95% CI -0.05 to 0.12) reduce axial length. There was inconclusive evidence on whether treatment cessation increases myopia progression. Adverse events and treatment adherence were not consistently reported, and only one study reported quality of life. No studies reported environmental interventions reporting progression in children with myopia, and no economic evaluations assessed interventions for myopia control in children. AUTHORS' CONCLUSIONS: Studies mostly compared pharmacological and optical treatments to slow the progression of myopia with an inactive comparator. Effects at one year provided evidence that these interventions may slow refractive change and reduce axial elongation, although results were often heterogeneous. A smaller body of evidence is available at two or three years, and uncertainty remains about the sustained effect of these interventions. Longer-term and better-quality studies comparing myopia control interventions used alone or in combination are needed, and improved methods for monitoring and reporting adverse effects.

ANTECEDENTES: La miopía es un defecto de refracción frecuente, en el que el alargamiento del globo ocular hace que los objetos lejanos aparezcan borrosos. La creciente prevalencia de la miopía es un problema de salud pública mundial cada vez mayor, en cuanto a tasas de defectos de refracción no corregidos y un significativamente mayor riesgo de discapacidad visual debido a la morbilidad ocular relacionada con la miopía. Dado que la miopía se suele detectar en niños antes de los 10 años y puede evolucionar rápidamente, las intervenciones para frenar su avance se deben realizar en la infancia. OBJETIVOS: Evaluar la eficacia comparativa de las intervenciones ópticas, farmacológicas y ambientales para frenar la progresión de la miopía en niños mediante un metanálisis en red (MAR). Generar una clasificación relativa de las intervenciones de control de la miopía en función de su eficacia. Elaborar un breve comentario económico que resuma las evaluaciones económicas de las intervenciones de control de la miopía en niños. Mantener la vigencia de la evidencia mediante un enfoque de revisión sistemática continua. MÉTODOS DE BÚSQUEDA: Se realizaron búsquedas en CENTRAL (que contiene el Registro de ensayos del Grupo Cochrane de Salud ocular y de la visión [Cochrane Eyes and Vision]), MEDLINE; Embase; y en tres registros de ensayos. La fecha de búsqueda fue el 26 de febrero de 2022. CRITERIOS DE SELECCIÓN: Se incluyeron ensayos controlados aleatorizados (ECA) de intervenciones ópticas, farmacológicas y ambientales para retrasar la progresión de la miopía en niños de hasta 18 años. Los desenlaces fundamentales fueron la progresión de la miopía (definida como la diferencia en el cambio del equivalente esférico de la refracción [EER, dioptrías (D)] y la longitud axial [mm] en los grupos de intervención y control al año o más) y la diferencia en el cambio del EER y la longitud axial tras el cese del tratamiento ("rebote"). OBTENCIÓN Y ANÁLISIS DE LOS DATOS: Se utilizaron los métodos Cochrane estándar. El sesgo se evaluó mediante la herramienta RoB 2 en el caso de los ECA paralelos. La certeza de la evidencia se calificó mediante el método GRADE para los desenlaces: cambio del EER y la longitud axial al año y a los dos años. La mayoría de las comparaciones se realizaron con controles inactivos. RESULTADOS PRINCIPALES: Se incluyeron 64 estudios que asignaron al azar a 11 617 niños de cuatro a 18 años de edad. Los estudios se realizaron principalmente en China u otros países asiáticos (39 estudios; 60,9%) y Norteamérica (13 estudios; 20,3%). Cincuenta y siete estudios (89%) compararon intervenciones de control de la miopía (gafas multifocales, gafas periféricas plus [PPSL por sus siglas en inglés], gafas monofocales [SVL por sus siglas en inglés] subcorregidas, lentes de contacto multifocales blandas [MFSCL por sus siglas en inglés], ortoqueratología, lentes de contacto rígidas permeables al gas [RGP por sus siglas en inglés]); o intervenciones farmacológicas (incluidas atropina a dosis alta, media y baja, pirenzipina o 7­metilxantina) contra un control inactivo. La duración de los estudios fue de 12 a 36 meses. La certeza global de la evidencia varió entre muy baja y moderada. Debido a que las redes del MAR estaban mal conectadas, la mayoría de las estimaciones versus control fueron tan imprecisas o más que las correspondientes estimaciones directas. En consecuencia, a continuación se presentan principalmente estimaciones basadas en comparaciones directas (por pares). Al año, en 38 estudios (6525 participantes analizados), la mediana del cambio del EER para los controles fue de ­0,65 D. Las siguientes intervenciones podrían reducir la progresión del EER en comparación con los controles: atropina a dosis alta (diferencia de medias [DM] 0,90 D; intervalo de confianza [IC] del 95%: 0,62 a 1,18), atropina a dosis media (DM 0,65 D; IC del 95%: 0,27 a 1,03), atropina a dosis baja (DM 0,38 D; IC del 95%: 0,10 a 0,66), pirenzipina (DM 0,32 D; IC del 95%: 0,15 a 0,49), MFSCL (DM 0,26 D; IC del 95%: 0,17 a 0,35), PPSL (DM 0,51 D; IC del 95%: 0,19 a 0,82) y gafas multifocales (DM 0,14 D; IC del 95%: 0,08 a 0,21). Por el contrario, hubo poca o ninguna evidencia de que las RGP (DM 0,02 D; IC del 95%: ­0,05 a 0,10), la 7­metilxantina (DM 0,07 D; IC del 95%: ­0,09 a 0,24) o las SVL subcorregidas (DM ­0,15 D; IC del 95%: ­0,29 a 0,00) redujeran la progresión. A los dos años, en 26 estudios (4949 participantes), el cambio medio del EER para los controles fue de ­1,02 D. Las siguientes intervenciones podrían reducir la progresión del EER en comparación con los controles: atropina a dosis alta (DM 1,26 D; IC del 95%: 1,17 a 1,36), atropina a dosis media (DM 0,45 D; IC del 95%: 0,08 a 0,83), atropina a dosis baja (DM 0,24 D; IC del 95%: 0,17 a 0,31), pirenzipina (DM 0,41 D; IC del 95%: 0,13 a 0,69), MFSCL (DM 0,30 D; IC del 95%: 0,19 a 0,41) y gafas multifocales (DM 0,19 D; IC del 95%: 0,08 a 0,30). Las PPSL (DM 0,34 D; IC del 95%: ­0,08 a 0,76) también podrían reducir la progresión, pero los resultados no fueron consistentes. Para las RGP, un estudio encontró un efecto beneficioso y otro no encontró diferencias con el control. No se observaron diferencias en el cambio del EER para las SVL subcorregidas (DM 0,02 D; IC del 95%: ­0,05 a 0,09). Al año, en 36 estudios (6.263 participantes), el cambio medio en la longitud axial de los controles fue de 0,31 mm. Las siguientes intervenciones podrían reducir la elongación axial en comparación con los controles: atropina a dosis alta (DM ­0,33 mm; IC 95%: ­0,35 a 0,30), atropina a dosis media (DM ­0,28 mm; IC 95%: ­0,38 a ­0,17), atropina a dosis baja (DM ­0,13 mm; IC 95%: ­0,21 a ­0,05), ortoqueratología (DM ­0,19 mm; IC 95%: ­0,23 a ­0,15), MFSCL (DM ­0,11 mm; IC del 95%: ­0,13 a ­0,09), pirenzipina (DM ­0,10 mm; IC del 95%: ­0,18 a ­0,02), PPSL (DM ­0,13 mm; IC del 95%: ­0,24 a ­0,03) y gafas multifocales (DM ­0,06 mm; IC del 95%: ­0,09 a ­0,04). Se encontró poca o ninguna evidencia de que las RGP (DM 0,02 mm; IC del 95%: ­0,05 a 0,10), la 7­metilxantina (DM 0,03 mm; IC del 95%: ­0,10 a 0,03) o las SVL subcorregidas (DM 0,05 mm; IC del 95%: ­0,01 a 0,11) reduzcan la longitud axial. A los dos años, en 21 estudios (4169 participantes), la mediana del cambio en la longitud axial de los controles fue de 0,56 mm. Las siguientes intervenciones podrían reducir la elongación axial en comparación con los controles: atropina a dosis alta (DM ­0,47 mm; IC del 95%: ­0,61 a ­0,34), atropina a dosis media (DM ­0,33 mm; IC del 95%: ­0,46 a ­0,20), ortoqueratología (DM ­0,28 mm; IC del 95%: ­0,38 a ­0,19), atropina a dosis baja (DM ­0,16 mm; IC del 95%: ­0,20 a ­0,12), MFSCL (DM ­0,15 mm; IC del 95%: ­0,19 a ­0,12) y gafas multifocales (DM ­0,07 mm; IC del 95%: ­0,12 a ­0,03). Las PPSL podrían reducir la progresión (DM ­0,20 mm; IC del 95%: ­0,45 a 0,05), pero los resultados no fueron consistentes. Se encontró poca o ninguna evidencia de que las SVL subcorregidas (DM ­0,01 mm; IC del 95%: ­0,06 a 0,03) o las RGP (DM 0,03 mm; IC del 95%: ­0,05 a 0,12) reduzcan la longitud axial. No hubo evidencia concluyente sobre si el abandono del tratamiento aumenta la progresión de la miopía. Los eventos adversos y la adherencia al tratamiento no se comunicaron de forma consistente, y solo un estudio informó sobre la calidad de vida. Ningún estudio proporcionó información sobre intervenciones ambientales que informaran sobre la progresión en niños con miopía y ninguna evaluación económica analizó intervenciones para el control de la miopía en niños. CONCLUSIONES DE LOS AUTORES: La mayoría de los estudios compararon tratamientos farmacológicos y ópticos para enlentecer la progresión de la miopía con un comparador inactivo. Los efectos al año demostraron que estas intervenciones podrían ralentizar el cambio refractivo y reducir el alargamiento axial, aunque a menudo los resultados fueron heterogéneos. El conjunto de evidencia disponible a los dos o tres años fue más escaso, y persiste la incertidumbre sobre el efecto sostenido de estas intervenciones. Se necesitan estudios a más largo plazo y de mejor calidad que comparen las intervenciones para el control de la miopía utilizadas solas o en combinación, así como métodos mejorados de seguimiento y notificación de los efectos adversos.

Symptoms and ocular findings associated with administration of 0.01% atropine in young adults.

CLINICAL RELEVANCE: This paper provides eye care practitioners with important information about the potential side effects of 0.01% atropine. BACKGROUND: Eye care practitioners routinely administer 0.01% atropine eye drops nightly to slow the progression of myopia, but nobody has assessed accommodative lag or facility, near phoria, intraocular pressure or comfort of drop administration. METHODS: All 21- to 30-year-old adults with no history of accommodative issues or therapy were eligible. During the baseline visit, participants underwent testing related to potential side effects. Participants then administered one drop of 0.01% atropine nightly to both eyes, and all tests were repeated 1 week later. RESULTS: The average ± standard deviation age of the 31 participants was 23.9 ± 1.6 years, 71% were female, and 81% were Caucasian. The only significant changes were an increase in photopic pupil size from 4.9 ± 0.8 at baseline to 5.1 ± 0.6 mm after 1 week (paired sample t-test, p = 0.002) and an increase of the average intraocular pressure of the two eyes from 15.6 ± 2.7 to 16.7 ± 3.1 mmHg (paired-sample t-test, p = 0.003), but neither of these changes was clinically meaningful. There were no other statistically significant differences before and after 1-week administration of 0.01% atropine for any of the vision, accommodation, reading speed or subjective side effects. When asked how likely they would be to take the atropine drops to delay the onset of myopia on a scale from 1 (definitely not) to 10 (definitely would), participants replied with an average of 8.2 ± 2.0 after taking atropine eye drops for 1 week (paired-sample t-test, p = 0.81). CONCLUSION: Nightly administration of 0.01% atropine did not result in any clinically meaningful symptoms, so patients would be very likely to take the drops to delay the onset of myopia.

The Effect of Multifocal Soft Contact Lens Wear on Axial and Peripheral Eye Elongation in the BLINK Study.

Purpose: The purpose of this study was to compare axial and peripheral eye elongation during myopia therapy with multifocal soft contact lenses. Methods: Participants were 294 children (177 [60.2%] girls) age 7 to 11 years old with between -0.75 diopters (D) and -5.00 D of myopia (spherical component) and less than 1.00 D astigmatism at baseline. Children were randomly assigned to Biofinity soft contact lenses for 3 years: D-designs with a +2.50 D addition, +1.50 D addition, or single vision. Five measurements of eye length were averaged at the fovea, ±20°, and ±30° in the horizontal and vertical meridians of the right eye using the Haag-Streit Lenstar LS 900. Results: Axial elongation over 3 years with single vision contact lenses was greater than peripheral elongation in the superior and temporal retinal qeuadrants by 0.07 mm (95% confidence interval [CI] = 0.05 to 0.09 mm) and 0.06 mm (95% CI = 0.03 to 0.09 mm) and similar in the inferior and nasal quadrants. Axial elongation with +2.50 D addition multifocal contact lenses was similar to peripheral elongation in the superior retinal quadrant and less than peripheral elongation in the inferior and nasal quadrants by -0.04 mm (95% CI = -0.06 to -0.01 mm) and -0.06 mm (95% CI = -0.09 to -0.02 mm). Conclusions: Wearing +2.50 D addition multifocal contact lenses neutralized or reversed the increase in retinal steepness with single vision lenses. The mismatch between greater inhibition of elongation at the fovea than peripherally despite greater peripheral myopic defocus suggests that optical myopia therapy may operate through extensive spatial integration or mechanisms other than local defocus.

Effect of Combining 0.01% Atropine with Soft Multifocal Contact Lenses on Myopia Progression in Children.

SIGNIFICANCE: Combining 0.01% atropine with soft multifocal contact lenses (SMCLs) failed to demonstrate better myopia control than SMCLs alone. PURPOSE: The Bifocal & Atropine in Myopia (BAM) Study investigated whether combining 0.01% atropine and SMCLs with +2.50-D add power leads to greater slowing of myopia progression and axial elongation than SMCLs alone. METHODS: Participants of the BAM Study wore SMCLs with +2.50-D add power daily and administered 0.01% atropine eye drops nightly (n = 46). The BAM subjects (bifocal-atropine) were age-matched to 46 participants in the Bifocal Lenses in Nearsighted Kids Study who wore SMCLs with +2.50-D add power (bifocal) and 46 Bifocal Lenses in Nearsighted Kids participants who wore single-vision contact lenses (single vision). The primary outcome was the 3-year change in spherical equivalent refractive error determined by cycloplegic autorefraction, and the 3-year change in axial elongation was also evaluated. RESULTS: Of the total 138 subjects, the mean ± standard deviation age was 10.1 ± 1.2 years, and the mean ± standard deviation spherical equivalent was -2.28 ± 0.89 D. The 3-year adjusted mean myopia progression was -0.52 D for bifocal-atropine, -0.55 D for bifocal, and -1.09 D for single vision. The difference in myopia progression was 0.03 D (95% confidence interval [CI], -0.14 to 0.21 D) for bifocal-atropine versus bifocal and 0.57 D (95% CI, 0.38 to 0.77 D) for bifocal-atropine versus single vision. The 3-year adjusted axial elongation was 0.31 mm for bifocal-atropine, 0.39 mm for bifocal, and 0.68 mm for single vision. The difference in axial elongation was -0.08 mm (95% CI, -0.16 to 0.002 mm) for bifocal-atropine versus bifocal and -0.37 mm (95% CI, -0.46 to -0.28 mm) for bifocal-atropine versus single vision. CONCLUSIONS: Adding 0.01% atropine to SMCLs with +2.50-D add power failed to demonstrate better myopia control than SMCLs alone.

Ocular and Nonocular Adverse Events during 3 Years of Soft Contact Lens Wear in Children.

SIGNIFICANCE: Children are being fitted at younger ages with soft contact lenses for myopia control. This 3-year investigation of adverse events related to contact lens wear in 7- to 11-year-old participants helps optometrists understand what to expect when fitting children with soft contact lenses. PURPOSE: The purpose of this article is to report the frequency and type of ocular and nonocular adverse events related to soft contact lens wear in children. METHODS: Seven- to 11-year-old children wore soft contact lenses for 3 years. Adverse events were defined by a slit-lamp examination finding of grade 3 or worse; parental report of a clinically meaningful change (determined by the examiner) in eyes, vision, or health; or a clinically meaningful response (determined by examiner) to a symptom checklist. Adverse events were categorized and reported by examiners and finalized by the Executive Committee. The presence or absence of an infiltrate and a list of diagnoses was determined at the conclusion of the study. RESULTS: The 294 participants wore their contact lenses 73.0 ± 26.5 hours per week, and 220 (74.8%) encountered at least 1 adverse event. Of the 432 adverse events, 75.2% were ocular, and 24.8% were nonocular. Contact lens wear was probably or definitely related to 60.6% of the ocular and 2.8% of the nonocular adverse events. None of the ocular adverse events were serious or severe or caused permanent contact lens discontinuation. The corneal infiltrate incidence was 185 cases per 10,000 patient-years of wear (95% confidence interval, 110 to 294). The incidence of moderate ocular adverse events that were definitely or probably related to contact lens wear was 405 cases per 10,000 patient-years of wear (95% confidence interval, 286 to 557). CONCLUSIONS: The adverse events experienced by 7- to 11-year-old myopic children rarely required meaningful treatment and never led to permanent discontinuation of contact lens wear or loss of best-corrected vision.

Visual Performance with Spherical and Multifocal Contact Lenses in a Pediatric Population.

SIGNIFICANCE: This pilot study compared subjective and objective vision of children wearing single-vision and +2.00, +3.00, and +4.00 D add power soft multifocal contact lenses to determine whether the higher add power-thought to provide better myopia control-resulted in visual compromise. PURPOSE: This study aimed to determine the maximum add power children wearing center-distance soft multifocal contact lenses could accept objectively and subjectively. METHODS: Myopic children were assigned in random order to wear omafilcon A single-vision or multifocal "D" contact lenses with +2.00, +3.00, or +4.00 D add power for 1 week each. High-contrast distance and near visual acuity, low-contrast distance visual acuity, and contrast sensitivity were measured at each visit along with a quality of vision questionnaire to assess their vision. The Friedman test was performed to evaluate the impact of add power on all outcome measures. RESULTS: Eleven subjects were enrolled, and nine subjects completed the study. The median age of completed subjects was 11 years. Median logMAR low-contrast distance visual acuity was reduced in the +3.00 (+0.20) and +4.00 (+0.28) D add lenses compared with the +2.00 (+0.16) D add and single-vision lenses (+0.10, P < .001). All three multifocal lenses resulted in reduced contrast sensitivity (+1.35 to +1.40) compared with single-vision lenses (+1.60, P < .001). In general, +3.00 and +4.00 D add lenses resulted in worse glare/starbursts, ghost images, computer vision, changing fixation distance, and overall vision, but results varied. There were no differences among the lenses with respect to subjective assessments of distance vision, near vision, strain or tiredness, contact lens comfort, or sporting activities. CONCLUSIONS: The +3.00 D and higher add powers result in more objective and subjective vision-related issues than single-vision lenses, but the +2.00 D add multifocal lenses were well tolerated.

IMI Prevention of Myopia and Its Progression.

The prevalence of myopia has markedly increased in East and Southeast Asia, and pathologic consequences of myopia, including myopic maculopathy and high myopia-associated optic neuropathy, are now some of the most common causes of irreversible blindness. Hence, strategies are warranted to reduce the prevalence of myopia and the progression to high myopia because this is the main modifiable risk factor for pathologic myopia. On the basis of published population-based and interventional studies, an important strategy to reduce the development of myopia is encouraging schoolchildren to spend more time outdoors. As compared with other measures, spending more time outdoors is the safest strategy and aligns with other existing health initiatives, such as obesity prevention, by promoting a healthier lifestyle for children and adolescents. Useful clinical measures to reduce or slow the progression of myopia include the daily application of low-dose atropine eye drops, in concentrations ranging between 0.01% and 0.05%, despite the side effects of a slightly reduced amplitude of accommodation, slight mydriasis, and risk of an allergic reaction; multifocal spectacle design; contact lenses that have power profiles that produce peripheral myopic defocus; and orthokeratology using corneal gas-permeable contact lenses that are designed to flatten the central cornea, leading to midperipheral steeping and peripheral myopic defocus, during overnight wear to eliminate daytime myopia. The risk-to-benefit ratio needs to be weighed up for the individual on the basis of their age, health, and lifestyle. The measures listed above are not mutually exclusive and are beginning to be examined in combination.

IMI Impact of Myopia.

The global burden of myopia is growing. Myopia affected nearly 30% of the world population in 2020 and this number is expected to rise to 50% by 2050. This review aims to analyze the impact of myopia on individuals and society; summarizing the evidence for recent research on the prevalence of myopia and high myopia, lifetime pathological manifestations of myopia, direct health expenditure, and indirect costs such as lost productivity and reduced quality of life (QOL). The principal trends are a rising prevalence of myopia and high myopia, with a disproportionately greater increase in the prevalence of high myopia. This forecasts a future increase in vision loss due to uncorrected myopia as well as high myopia-related complications such as myopic macular degeneration. QOL is affected for those with uncorrected myopia, high myopia, or complications of high myopia. Overall the current global cost estimates related to direct health expenditure and lost productivity are in the billions. Health expenditure is greater in adults, reflecting the added costs due to myopia-related complications. Unless the current trajectory for the rising prevalence of myopia and high myopia change, the costs will continue to grow. The past few decades have seen the emergence of several novel approaches to prevent and slow myopia. Further work is needed to understand the life-long impact of myopia on an individual and the cost-effectiveness of the various novel approaches in reducing the burden.

Contact Lens Adaption in Neophytes.

SIGNIFICANCE: Clinicians commonly either recommend patients begin contact lens (CL) wear full time or suggest that patients should gradually increase their wear times during the first few days of wear. This study found no differences between these two wear schedules, suggesting that patient preference may be the best schedule. PURPOSE: The purpose of this study was to determine if there are any clinical differences in neophyte, 2-week, reusable soft CL wearers who were randomized to either a full-time or a gradually increasing wear time schedule. METHODS: This was an investigator-masked, three-visit, randomized, clinical trial. Participants were randomized to wear their CLs full time starting on the first day or gradually starting with 2 hours of wear on the first day and increasing wear by 2 hours each day until 8 hours or more of wear per day was achieved. Symptoms (Ocular Surface Disease Index and visual analog scale) and ocular surface signs (tear breakup time, extent of corneal staining, and Schirmer test I) were evaluated at each visit. RESULTS: A total of 25 participants were randomized, with 21 participants completing at least 1 week of follow-up. Completed participants had a mean ± standard deviation age of 23.5 ± 3.0 years, and 48% were female. No significant between-group differences were found when comparing the full-time and gradual wear time schedule groups at 2 weeks (all, P > .32): Ocular Surface Disease Index (10.8 ± 8.5 vs. 16.3 ± 18.8), visual analog scale (89.0 ± 9.7 vs. 81.8 ± 18.7), tear breakup time (11.7 ± 7.0 vs. 9.8 ± 2.7), extent of corneal staining (0.0 ± 0.1 vs. 0.3 ± 0.5), or Schirmer test I (15.9 ± 8.8 vs. 21.2 ± 12.5). CONCLUSIONS: No between-group differences were found for any metric evaluated, which suggests that the best wear schedule may be the one that best suits the neophyte CL wearer's lifestyle.

Effect of High Add Power, Medium Add Power, or Single-Vision Contact Lenses on Myopia Progression in Children: The BLINK Randomized Clinical Trial.

Importance: Slowing myopia progression could decrease the risk of sight-threatening complications. Objective: To determine whether soft multifocal contact lenses slow myopia progression in children, and whether high add power (+2.50 D) slows myopia progression more than medium (+1.50 D) add power lenses. Design, Setting, and Participants: A double-masked randomized clinical trial that took place at 2 optometry schools located in Columbus, Ohio, and Houston, Texas. A total of 294 consecutive eligible children aged 7 to 11 years with -0.75 D to -5.00 D of spherical component myopia and less than 1.00 D astigmatism were enrolled between September 22, 2014, and June 20, 2016. Follow-up was completed June 24, 2019. Interventions: Participants were randomly assigned to wear high add power (n = 98), medium add power (n = 98), or single-vision (n = 98) contact lenses. Main Outcomes and Measures: The primary outcome was the 3-year change in cycloplegic spherical equivalent autorefraction, as measured by the mean of 10 autorefraction readings. There were 11 secondary end points, 4 of which were analyzed for this study, including 3-year eye growth. Results: Among 294 randomized participants, 292 (99%) were included in the analyses (mean [SD] age, 10.3 [1.2] years; 177 [60.2%] were female; mean [SD] spherical equivalent refractive error, -2.39 [1.00] D). Adjusted 3-year myopia progression was -0.60 D for high add power, -0.89 D for medium add power, and -1.05 D for single-vision contact lenses. The difference in progression was 0.46 D (95% CI, 0.29-0.63) for high add power vs single vision, 0.30 D (95% CI, 0.13-0.47) for high add vs medium add power, and 0.16 D (95% CI, -0.01 to 0.33) for medium add power vs single vision. Of the 4 secondary end points, there were no statistically significant differences between the groups for 3 of the end points. Adjusted mean eye growth was 0.42 mm for high add power, 0.58 mm for medium add power, and 0.66 mm for single vision. The difference in eye growth was -0.23 mm (95% CI, -0.30 to -0.17) for high add power vs single vision, -0.16 mm (95% CI, -0.23 to -0.09) for high add vs medium add power, and -0.07 mm (95% CI, -0.14 to -0.01) for medium add power vs single vision. Conclusions and Relevance: Among children with myopia, treatment with high add power multifocal contact lenses significantly reduced the rate of myopia progression over 3 years compared with medium add power multifocal and single-vision contact lenses. However, further research is needed to understand the clinical importance of the observed differences. Trial Registration: ClinicalTrials.gov Identifier: NCT02255474.

Interventions to slow progression of myopia in children.

BACKGROUND: Nearsightedness (myopia) causes blurry vision when one is looking at distant objects. Interventions to slow the progression of myopia in children include multifocal spectacles, contact lenses, and pharmaceutical agents. OBJECTIVES: To assess the effects of interventions, including spectacles, contact lenses, and pharmaceutical agents in slowing myopia progression in children. SEARCH METHODS: We searched CENTRAL; Ovid MEDLINE; Embase.com; PubMed; the LILACS Database; and two trial registrations up to February 2018. A top up search was done in February 2019. SELECTION CRITERIA: We included randomized controlled trials (RCTs). We excluded studies when most participants were older than 18 years at baseline. We also excluded studies when participants had less than -0.25 diopters (D) spherical equivalent myopia. DATA COLLECTION AND ANALYSIS: We followed standard Cochrane methods. MAIN RESULTS: We included 41 studies (6772 participants). Twenty-one studies contributed data to at least one meta-analysis. Interventions included spectacles, contact lenses, pharmaceutical agents, and combination treatments. Most studies were conducted in Asia or in the United States. Except one, all studies included children 18 years or younger. Many studies were at high risk of performance and attrition bias. Spectacle lenses: undercorrection of myopia increased myopia progression slightly in two studies; children whose vision was undercorrected progressed on average -0.15 D (95% confidence interval [CI] -0.29 to 0.00; n = 142; low-certainty evidence) more than those wearing fully corrected single vision lenses (SVLs). In one study, axial length increased 0.05 mm (95% CI -0.01 to 0.11) more in the undercorrected group than in the fully corrected group (n = 94; low-certainty evidence). Multifocal lenses (bifocal spectacles or progressive addition lenses) yielded small effect in slowing myopia progression; children wearing multifocal lenses progressed on average 0.14 D (95% CI 0.08 to 0.21; n = 1463; moderate-certainty evidence) less than children wearing SVLs. In four studies, axial elongation was less for multifocal lens wearers than for SVL wearers (-0.06 mm, 95% CI -0.09 to -0.04; n = 896; moderate-certainty evidence). Three studies evaluating different peripheral plus spectacle lenses versus SVLs reported inconsistent results for refractive error and axial length outcomes (n = 597; low-certainty evidence). Contact lenses: there may be little or no difference between vision of children wearing bifocal soft contact lenses (SCLs) and children wearing single vision SCLs (mean difference (MD) 0.20D, 95% CI -0.06 to 0.47; n = 300; low-certainty evidence). Axial elongation was less for bifocal SCL wearers than for single vision SCL wearers (MD -0.11 mm, 95% CI -0.14 to -0.08; n = 300; low-certainty evidence). Two studies investigating rigid gas permeable contact lenses (RGPCLs) showed inconsistent results in myopia progression; these two studies also found no evidence of difference in axial elongation (MD 0.02mm, 95% CI -0.05 to 0.10; n = 415; very low-certainty evidence). Orthokeratology contact lenses were more effective than SVLs in slowing axial elongation (MD -0.28 mm, 95% CI -0.38 to -0.19; n = 106; moderate-certainty evidence). Two studies comparing spherical aberration SCLs with single vision SCLs reported no difference in myopia progression nor in axial length (n = 209; low-certainty evidence). Pharmaceutical agents: at one year, children receiving atropine eye drops (3 studies; n = 629), pirenzepine gel (2 studies; n = 326), or cyclopentolate eye drops (1 study; n = 64) showed significantly less myopic progression compared with children receiving placebo: MD 1.00 D (95% CI 0.93 to 1.07), 0.31 D (95% CI 0.17 to 0.44), and 0.34 (95% CI 0.08 to 0.60), respectively (moderate-certainty evidence). Axial elongation was less for children treated with atropine (MD -0.35 mm, 95% CI -0.38 to -0.31; n = 502) and pirenzepine (MD -0.13 mm, 95% CI -0.14 to -0.12; n = 326) than for those treated with placebo (moderate-certainty evidence) in two studies. Another study showed favorable results for three different doses of atropine eye drops compared with tropicamide eye drops (MD 0.78 D, 95% CI 0.49 to 1.07 for 0.1% atropine; MD 0.81 D, 95% CI 0.57 to 1.05 for 0.25% atropine; and MD 1.01 D, 95% CI 0.74 to 1.28 for 0.5% atropine; n = 196; low-certainty evidence) but did not report axial length. Systemic 7-methylxanthine had little to no effect on myopic progression (MD 0.07 D, 95% CI -0.09 to 0.24) nor on axial elongation (MD -0.03 mm, 95% CI -0.10 to 0.03) compared with placebo in one study (n = 77; moderate-certainty evidence). One study did not find slowed myopia progression when comparing timolol eye drops with no drops (MD -0.05 D, 95% CI -0.21 to 0.11; n = 95; low-certainty evidence). Combinations of interventions: two studies found that children treated with atropine plus multifocal spectacles progressed 0.78 D (95% CI 0.54 to 1.02) less than children treated with placebo plus SVLs (n = 191; moderate-certainty evidence). One study reported -0.37 mm (95% CI -0.47 to -0.27) axial elongation for atropine and multifocal spectacles when compared with placebo plus SVLs (n = 127; moderate-certainty evidence). Compared with children treated with cyclopentolate plus SVLs, those treated with atropine plus multifocal spectacles progressed 0.36 D less (95% CI 0.11 to 0.61; n = 64; moderate-certainty evidence). Bifocal spectacles showed small or negligible effect compared with SVLs plus timolol drops in one study (MD 0.19 D, 95% CI 0.06 to 0.32; n = 97; moderate-certainty evidence). One study comparing tropicamide plus bifocal spectacles versus SVLs reported no statistically significant differences between groups without quantitative results. No serious adverse events were reported across all interventions. Participants receiving antimuscarinic topical medications were more likely to experience accommodation difficulties (Risk Ratio [RR] 9.05, 95% CI 4.09 to 20.01) and papillae and follicles (RR 3.22, 95% CI 2.11 to 4.90) than participants receiving placebo (n=387; moderate-certainty evidence). AUTHORS' CONCLUSIONS: Antimuscarinic topical medication is effective in slowing myopia progression in children. Multifocal lenses, either spectacles or contact lenses, may also confer a small benefit. Orthokeratology contact lenses, although not intended to modify refractive error, were more effective than SVLs in slowing axial elongation. We found only low or very low-certainty evidence to support RGPCLs and sperical aberration SCLs.

Bifocal & Atropine in Myopia Study: Baseline Data and Methods.

SIGNIFICANCE: The Bifocal & Atropine in Myopia (BAM) study aims to determine whether combining 0.01% atropine and +2.50-diopter add center-distance soft bifocal contact lenses (SBCL) slows myopia progression more than SBCL alone. The results could provide significant information on the myopia control effect of combining optical and pharmacological treatments. PURPOSE: This article describes the subject characteristics at baseline, the study methods, and the short-term effects of this combination treatment on visual acuity (VA) and vision-related outcomes. METHODS: Subjects from the BAM study who met the baseline eligibility criteria were dispensed the combination treatment for 2 weeks to determine final eligibility. Outcome measures included VA at near and distance (Bailey-Lovie logMAR charts), near phoria (modified Thorington), accommodative lag (Grand Seiko WAM-5500), and pupil size (NeurOptics VIP-200 Pupillometer). Compliance was monitored using surveys. Two subgroups in the Bifocal Lenses In Nearsighted Kids study, single-vision contact lens wearers and those who wore +2.50-diopter add SBCL, will serve as the age-matched historical controls for BAM study. RESULTS: Forty-nine BAM subjects (9.6 ± 1.4 years) were enrolled; mean spherical equivalent cycloplegic autorefraction was -2.33 ± 1.03 diopters. After 2 weeks of treatment, the best-corrected low-contrast (10% Michelson) distance VA was reduced (pre-treatment, +0.09 ± 0.07; post-treatment, +0.16 ± 0.08; P < .0001), but the high-contrast VA at near or distance was unaffected. Near phoria increased by approximately 2 in the exo direction (P = .01), but the accommodative lag was unchanged. The pupil size was not significantly different between pre-treatment and post-treatment of either the photopic or mesopic condition. Surveys indicated that the subjects wore SBCL 77 ± 22% of waking hours and used atropine 6.4 ± 0.7 days per week. CONCLUSIONS: Two weeks of combination treatment reduced low-contrast distance VA and increased near exophoria slightly, but the subjects were compliant and tolerated the treatment well.

Peripheral Refraction and Eye Lengths in Myopic Children in the Bifocal Lenses In Nearsighted Kids (BLINK) Study.

PURPOSE: Provide a detailed assessment of peripheral refractive error and peripheral eye length in myopic children. METHODS: Subjects were 294 children aged 7 to 11 years with -0.75 to -5.00 diopter (D) of myopia by cycloplegic autorefraction. Peripheral refraction and eye length were measured at ±20° and ±30° horizontally and vertically, with peripheral refraction also measured at ±40° horizontally. RESULTS: Relative peripheral refraction became more hyperopic in the horizontal meridian and more myopic in the vertical meridian with increasing field angle. Peripheral eye length became shorter in both meridians with increasing field angle, more so horizontally than vertically with correlations between refraction and eye length ranging from -0.40 to -0.57 (all P < 0.001). Greater foveal myopia was related to more peripheral hyperopia (or less peripheral myopia), shorter peripheral eye lengths, and a consistent average asymmetry between meridians. CONCLUSIONS: Peripheral refractive errors in children do not appear to exert strong local control of peripheral eye length given that their correlation is consistently negative and the degree of meridional asymmetry is similar across the range of refractive errors. The BLINK study will provide longitudinal data to determine whether peripheral myopia and additional peripheral myopic defocus from multifocal contact lenses affect the progression of myopia in children. TRANSLATIONAL RELEVANCE: Local retinal control of ocular growth has been demonstrated numerous times in animal experimental myopia models but has not been explored in detail in human myopia development. These BLINK baseline results suggest that children's native peripheral optical signals may not be a strong stimulus for local growth responses.

IMI - Interventions Myopia Institute: Interventions for Controlling Myopia Onset and Progression Report.

Myopia has been predicted to affect approximately 50% of the world's population based on trending myopia prevalence figures. Critical to minimizing the associated adverse visual consequences of complicating ocular pathologies are interventions to prevent or delay the onset of myopia, slow its progression, and to address the problem of mechanical instability of highly myopic eyes. Although treatment approaches are growing in number, evidence of treatment efficacy is variable. This article reviews research behind such interventions under four categories: optical, pharmacological, environmental (behavioral), and surgical. In summarizing the evidence of efficacy, results from randomized controlled trials have been given most weight, although such data are very limited for some treatments. The overall conclusion of this review is that there are multiple avenues for intervention worthy of exploration in all categories, although in the case of optical, pharmacological, and behavioral interventions for preventing or slowing progression of myopia, treatment efficacy at an individual level appears quite variable, with no one treatment being 100% effective in all patients. Further research is critical to understanding the factors underlying such variability and underlying mechanisms, to guide recommendations for combined treatments. There is also room for research into novel treatment options.