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Respiratory Medicine Oct 2020Regular physical activity is strongly recommended to prevent chronic respiratory diseases, including asthma. On the other hand, vigorous physical training may trigger...
Regular physical activity is strongly recommended to prevent chronic respiratory diseases, including asthma. On the other hand, vigorous physical training may trigger airway symptoms and bronchoconstriction. The transient airway narrowing occurring because of exercise is named exercise-induced bronchoconstriction (EIB). Despite management according to guidelines, a significant proportion of patients experiences uncontrolled EIB, which thus represents a relevant unmet medical need. In particular, although prevention and treatment of EIB are effectively based on the use of beta-2 bronchodilator drugs, high heterogeneity in individual responses has been reported. Furthermore, even though beta-2 adrenergic drugs remain the mainstay of EIB management, occurrence of tolerance and side effects, as well as doping concerns have been reported with their use. In regard to this, inhaled antimuscarinics could represent an alternative or additional effective and safe bronchodilator therapeutic option for achieving optimal EIB control and minimize adverse events. The present systematic review aims to collect and provide the most updated and evidence-based literature findings on the efficacy and safety of short- and long-acting inhaled anti-muscarinic drugs for the preventive treatment of EIB in both children and adults. Take-Home Message: Anti-muscarinic drugs are effective and safe in preventing EIB, despite response variability is reported. Further studies should focus on long-acting molecules, chronic administration and phenotype-driven effects.
Topics: Administration, Inhalation; Adolescent; Adult; Bronchoconstriction; Bronchodilator Agents; Child; Delayed-Action Preparations; Female; Humans; Male; Muscarinic Antagonists; Physical Conditioning, Human; Respiratory Hypersensitivity; Young Adult
PubMed: 32911137
DOI: 10.1016/j.rmed.2020.106128 -
International Journal of Chronic... 2020This literature review assessed comparative efficacy and safety of long-acting muscarinic antagonist/long-acting β-agonist (LAMA/LABA) fixed-dose combinations (FDCs) in...
Efficacy and Safety of LAMA/LABA Fixed-Dose Combination Therapies in Chronic Obstructive Pulmonary Disease: A Systematic Review of Direct and Indirect Treatment Comparisons.
BACKGROUND
This literature review assessed comparative efficacy and safety of long-acting muscarinic antagonist/long-acting β-agonist (LAMA/LABA) fixed-dose combinations (FDCs) in patients with COPD and moderate-to-very severe airflow limitation, using evidence from direct (head-to-head) and indirect treatment comparisons.
METHODS
Two systematic literature reviews were conducted to identify direct comparisons (head-to-head randomized controlled trials [RCTs]) and indirect comparisons (network meta-analyses [NMAs]; indirect treatment comparisons; meta-analyses) in patients with COPD with moderate-to-very severe airflow limitation. Study/Analysis characteristics, eligibility criteria, patient characteristics, and overall conclusions were extracted from relevant publications. The review of indirect comparisons focused on NMAs reporting efficacy outcomes at 12 and 24 weeks of treatment (established durations of symptomatic studies in COPD recommended by regulators).
RESULTS
Four RCTs that provided head-to-head comparisons of LAMA/LABA FDCs were identified, and these varied in their study design, included patient population and reported endpoints. While some differences in lung function outcomes were noted, where assessed, LAMA/LABA FDCs had comparable efficacy in improving symptoms, health status, exacerbations, and comparable safety profiles. However, the differences in study methodology and patient characteristics between these studies made it difficult to draw generalizable conclusions regarding the comparative effectiveness of LAMA/LABA FDCs from the direct comparisons alone. Six NMAs were identified that reported indirect comparisons between LAMA/LABA FDCs; five of these were within the pre-defined scope of this review. Although the scope of each NMA varied, all five concluded that LAMA/LABA FDCs were generally comparable in terms of lung function improvements, patient-reported outcomes, and safety (where assessed).
CONCLUSION
Although there were some inconsistencies between the outcomes of RCTs and NMAs for lung function, the totality of lung function, symptoms, exacerbations, and safety data suggests that currently available LAMA/LABA FDCs have comparable efficacy and safety in patients with COPD and moderate-to-very severe airflow limitation.
Topics: Administration, Inhalation; Adrenergic beta-2 Receptor Agonists; Bronchodilator Agents; Drug Combinations; Humans; Lung; Muscarinic Antagonists; Pulmonary Disease, Chronic Obstructive
PubMed: 32669839
DOI: 10.2147/COPD.S230955 -
Therapeutic Advances in Respiratory... 2020Long-acting muscarinic antagonist (LAMA) monotherapy is recommended for chronic obstructive pulmonary disease (COPD) patients with high risk of exacerbations. It is... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Long-acting muscarinic antagonist (LAMA) monotherapy is recommended for chronic obstructive pulmonary disease (COPD) patients with high risk of exacerbations. It is unclear whether long-acting β2-agonist (LABA)/LAMA fixed-dose combinations (FDCs) are more effective than LAMAs alone in preventing exacerbations. The aim of this study was to systematically review the literature to investigate whether LABA/LAMA FDCs are more effective than LAMA monotherapy in preventing exacerbations.
METHODS
We searched several databases and manufacturers' websites to identify relevant randomized clinical trials comparing LABA/LAMA FDC treatment with LAMAs alone ⩾24 weeks. Outcomes of interest were time to first exacerbation and rates of moderate to severe, severe and all exacerbations.
RESULTS
We included 10 trials in 9 articles from 2013 to 2018 with a total of 19,369 patients for analysis in this study. Compared with LAMA monotherapy, LABA/LAMA FDCs demonstrated similar efficacy in terms of time to first exacerbation [hazard ratio, 0.96; 95% confidence interval (CI) 0.79-1.18; = 0.71], moderate to severe exacerbations [risk ratio (RR), 0.96; 95% CI 0.90-1.03; = 0.28], severe exacerbations (RR, 0.92; 95% CI 0.81-1.03; = 0.15), and a marginal superiority in terms of all exacerbations (RR, 0.92; 95% CI 0.86-1.00; = 0.04). The incidence of all exacerbation events was lower in the LABA/LAMA FDC group for the COPD patients with a history of previous exacerbations and those with a longer treatment period (52-64 weeks).
CONCLUSION
This study provides evidence that LABA/LAMA FDCs are marginally superior in the prevention of all exacerbations compared with LAMA monotherapy in patients with COPD.
Topics: Adrenergic beta-2 Receptor Agonists; Aged; Bronchodilator Agents; Disease Progression; Drug Combinations; Female; Humans; Lung; Male; Middle Aged; Muscarinic Antagonists; Pulmonary Disease, Chronic Obstructive; Randomized Controlled Trials as Topic; Time Factors; Treatment Outcome
PubMed: 32643547
DOI: 10.1177/1753466620937194 -
BMC Ophthalmology May 2020Many treatments are currently available for amblyopic patients; although, the comparative efficacy of these therapies is unclear. We conducted a systematic review and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Many treatments are currently available for amblyopic patients; although, the comparative efficacy of these therapies is unclear. We conducted a systematic review and network meta-analysis (NMA) to establish the relative efficacy of these treatments for amblyopia.
METHODS
Electronic databases (MEDLINE, EMBASE, Cochrane Library) were systematically searched from inception to Sep. 2019. Only Randomized clinical trials comparing any two or three of the following treatments were included: refractive correction (spectacles alone), patching of 2 h per day (patch 2H), patch 6H, patch 12H, patch 2H + near activities (N), patch 2H + distant activities (D), atropine (Atr) daily, Atr weekly, Atr weekly + plano lens over the sound eye (Plano), optical penalization and binocular therapy. The reviewers independently extracted the data according to the PRISMA guidelines; assessed study quality by Cochrane risk-of-bias tool for randomized trials. The primary outcome measure was the change in best-corrected visual acuity (BCVA) expressed as log MAR lines. Direct comparisons and a Bayesian meta-analysis were performed to synthesize data.
RESULTS
Twenty-three studies with 3279 patients were included. In the network meta-analysis, optical penalization was the least effective of all the treatments for the change of visual acuity, spectacles (mean difference [MD], 2.9 Log MAR lines; 95% credibility interval [CrI], 1.8-4.0), patch 2H (MD, 3.3; 95% CrI, 2.3-4.3), patch 6H (MD, 3.6; 95% CrI, 2.6-4.6), patch 12H (MD, 3.4; 95% CrI, 2.3-4.5), patch 2H + N (MD, 3.7; 95% CrI, 2.5-5.0), patch 2H + D (MD, 3.5; 95% CrI, 2.1-5.0), Atr daily (MD, 3.2; 95% CrI, 2.2-4.3), Atr weekly (MD, 3.2; 95% CrI, 2.2-4.3), Atr weekly + Plano (MD, 3.7; 95% CrI, 2.7-4.7), binocular therapy (MD, 3.1; 95% CrI, 2.0-4.2). The patch 6H and patch 2H + N were better than spectacles ([MD, 0.73; 95% Crl, 0.10-1.40]; [MD, 0.84; 95% CrI, 0.19-1.50]).
CONCLUSIONS
The NMA indicated that the efficacy of the most of the examined treatment modalities for amblyopia were comparable, with no significant difference. Further high quality randomized controlled trials are required to determine their efficacy and acceptability.
SYSTEMATIC REVIEW REGISTRATION
CRD42019119843.
Topics: Amblyopia; Atropine; Child; Child, Preschool; Databases, Factual; Eyeglasses; Female; Humans; Infant; Infant, Newborn; Male; Muscarinic Antagonists; Network Meta-Analysis; Sensory Deprivation; Treatment Outcome; Vision, Binocular; Visual Acuity
PubMed: 32450849
DOI: 10.1186/s12886-020-01442-9 -
BMC Pregnancy and Childbirth May 2020The objective of this systematic review and meta-analysis was to assess the effectiveness of hyoscine n-butylbromide in labor progress. (Meta-Analysis)
Meta-Analysis
BACKGROUND
The objective of this systematic review and meta-analysis was to assess the effectiveness of hyoscine n-butylbromide in labor progress.
METHODS
The databases including PubMed, the Cochrane Library, Science-Direct, Scopus and Web of Science were searched for studies published up to December 2019. Articles that published as randomized controlled trials (RCTs), and full-text articles published in English or other languages were included and participants were primi or multigravida women who were in active phase of labor. The intervention included HBB compared to placebo (normal saline) that was used during active phase of labor. Pooled estimates were measured using the fixed or random effect model, while the overall effect was reported in a mean difference (MD). All data were analyzed using Review Manager 5.3.
RESULTS
Twenty studies involving 3108 women were included in meta-analysis. Based on subgroup analysis by parity, use of HBB significantly reduced the duration of the first stage of labor in primigravida women (MD = - 57.73; 95% CI: [- 61.48, - 53.60]) and in multigravida women (MD = - 90.74; 95% CI: [- 97.24, - 84.24]). Administering HBB could reduce the second stages of labor in primigravidas and multigravidas about 6 min and 4 min respectively. Also, HBB reduced the duration of the third stage of labor in multigravidas about 3 min. APGAR score at one and 5 min after birth was not affected. The main maternal adverse effect was tachycardia and dry mouth. Labor duration in studies in which the participants were primi-and multigravida was not presented based on separate parities except for four papers, and the route of HBB administration was not the same across all studies.
CONCLUSIONS
Although, the effect of HBB was minimal when multigravidas and primigravidas women were considered together, the HBB was clinically effective in primigravida and multigravida women for shortening the first and the second stages of labor. Also, HBB could reduce the length of the third stage of labor in multigravidas.
Topics: Adult; Apgar Score; Butylscopolammonium Bromide; Cholinergic Antagonists; Female; Gravidity; Humans; Labor Stage, First; Labor, Obstetric; Muscarinic Antagonists; Parity; Pregnancy; Scopolamine; Young Adult
PubMed: 32404072
DOI: 10.1186/s12884-020-2832-3 -
BMC Pulmonary Medicine Apr 2020Inhaled bronchodilators including long-acting beta-agonist (LABA) and long-acting muscarinic antagonist (LAMA) play a central role in the treatment of stable chronic... (Comparative Study)
Comparative Study Meta-Analysis
BACKGROUND
Inhaled bronchodilators including long-acting beta-agonist (LABA) and long-acting muscarinic antagonist (LAMA) play a central role in the treatment of stable chronic obstructive pulmonary disease (COPD). However, it is still unclear whether LABA or LAMA should be used for the initial treatment. Therefore, we conducted a systematic review and meta-analysis to evaluate the efficacy and safety of LABA versus LAMA in patients with stable COPD.
METHODS
We searched relevant randomized control trials (RCTs) with a period of treatment of at least 12 weeks and analyzed the exacerbations, quality of life, dyspnea score, lung function and adverse events as the outcomes of interest.
RESULTS
We carefully excluded unblinded data and identified a total of 19 RCTs (N = 28,211). LAMA significantly decreased the exacerbations compared to LABA (OR 0.85, 95% CI 0.74 to 0.98; P = 0.02). In St George's Respiratory Questionnaire and transitional dyspnoea index score, there were no differences between LABA and LAMA treatment. Compared to LABA, there was a small but significant increase in the trough FEV after LAMA treatment (Mean difference 0.02, 95% CI 0.01 to 0.03, P = 0.0006). In the safety components, there was no difference in the serious adverse events between LABA and LAMA. However, LAMA showed a significantly lower incidence of total adverse events compared to LABA (OR 0.92, 95% CI 0.86 to 0.98; P = 0.02).
CONCLUSION
Treatment with LAMA in stable COPD provided a significantly lower incidence of exacerbation and non-serious adverse events, and a higher trough FEV compared to LABA.
TRIAL REGISTRATION
(PROSPERO: CRD42019144764).
Topics: Adrenergic beta-2 Receptor Agonists; Disease Progression; Drug Administration Schedule; Drug Combinations; Forced Expiratory Volume; Humans; Muscarinic Antagonists; Nebulizers and Vaporizers; Pulmonary Disease, Chronic Obstructive; Quality of Life; Randomized Controlled Trials as Topic
PubMed: 32349720
DOI: 10.1186/s12890-020-1152-8 -
Advances in Therapy Jun 2020Triple inhaled corticosteroid/long-acting muscarinic antagonist/long-acting β-agonist (ICS/LAMA/LABA) combination therapy is recommended for patients with chronic... (Comparative Study)
Comparative Study Meta-Analysis
Efficacy of Budesonide/Glycopyrronium/Formoterol Fumarate Metered Dose Inhaler (BGF MDI) Versus Other Inhaled Corticosteroid/Long-Acting Muscarinic Antagonist/Long-Acting β-Agonist (ICS/LAMA/LABA) Triple Combinations in COPD: A Systematic Literature Review and Network Meta-analysis.
INTRODUCTION
Triple inhaled corticosteroid/long-acting muscarinic antagonist/long-acting β-agonist (ICS/LAMA/LABA) combination therapy is recommended for patients with chronic obstructive pulmonary disease (COPD) who experience further exacerbations/symptoms on dual LAMA/LABA or ICS/LABA therapy. The relative efficacy of budesonide/glycopyrronium/formoterol fumarate metered dose inhaler 320/18/9.6 µg (BGF MDI) in COPD was compared with other ICS/LAMA/LABA fixed-dose and open combination therapies in a network meta-analysis (NMA).
METHODS
A systematic literature review was conducted to identify randomized controlled trials of at least 10-week duration, including at least one fixed-dose or open combination triple therapy arm, in patients with moderate to very severe COPD. Studies were assessed for methodological quality and risk of bias. A three-level hierarchical Bayesian NMA model was used to determine the exacerbation rate per patient per year as well as the following outcomes at week 24: changes from baseline in pre-dose trough forced expiratory volume in 1 s (FEV), post-dose peak FEV, and St. George's Respiratory Questionnaire (SGRQ) total score; proportion of SGRQ responders; and Transition Dyspnea Index focal score. Change from baseline in rescue medication use over weeks 12-24 was also analyzed. Meta-regression and sensitivity analyses were used to assess heterogeneity across studies.
RESULTS
Eighteen studies (n = 29,232 patients) contributed to the NMA. ICS/LABA dual combinations were combined as a single treatment group to create a connected network. Across all outcomes, there were no statistically significant differences between BGF MDI and other triple ICS/LAMA/LABA fixed-dose (fluticasone furoate/umeclidinium/vilanterol and beclomethasone dipropionate/glycopyrronium/formoterol fumarate) and open combinations with data available within the network. Results from sensitivity analyses and meta-regression were consistent with the base-case scenario.
CONCLUSION
This NMA suggested that BGF MDI has comparable efficacy to other ICS/LAMA/LABA fixed-dose and open triple combination therapies in reducing exacerbations and improving lung function and symptoms in patients with moderate to very severe COPD. Further research is warranted as additional evidence regarding triple therapies, especially fixed-dose combinations, becomes available.
Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adrenergic beta-2 Receptor Agonists; Aged; Bayes Theorem; Bronchodilator Agents; Budesonide; Drug Combinations; Dyspnea; Female; Forced Expiratory Volume; Formoterol Fumarate; Fumarates; Glycopyrrolate; Humans; Male; Metered Dose Inhalers; Middle Aged; Muscarinic Agonists; Muscarinic Antagonists; Network Meta-Analysis; Pulmonary Disease, Chronic Obstructive; Respiratory Function Tests; Treatment Outcome
PubMed: 32335859
DOI: 10.1007/s12325-020-01311-3 -
The Cochrane Database of Systematic... Apr 2020Escalating awareness of the magnitude of the challenge posed by low levels of physical activity in people with chronic obstructive pulmonary disease (COPD) highlights... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Escalating awareness of the magnitude of the challenge posed by low levels of physical activity in people with chronic obstructive pulmonary disease (COPD) highlights the need for interventions to increase physical activity participation. The widely-accepted benefits of physical activity, coupled with the increasing availability of wearable monitoring devices to objectively measure participation, has led to a dramatic rise in the number and variety of studies that aimed to improve the physical activity of people with COPD. However, little was known about the relative efficacy of interventions tested so far.
OBJECTIVES
In people with COPD, which interventions are effective at improving objectively-assessed physical activity?
SEARCH METHODS
We identified trials from the Cochrane Airways Trials Register Register, which contains records identified from bibliographic databases including the Cochrane Central Register of Controlled Trials, MEDLINE, Embase, CINAHL, AMED, and PsycINFO. We also searched PEDro, ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform portal and the Australian New Zealand Clinical Trials Registry (from inception to June 2019). We checked reference lists of all primary studies and review articles for additional references, as well as respiratory journals and respiratory meeting abstracts, to identify relevant studies.
SELECTION CRITERIA
We included randomised controlled trials of interventions that used objective measures for the assessment of physical activity in people with COPD. Trials compared an intervention with no intervention or a sham/placebo intervention, an intervention in addition to another standard intervention common to both groups, or two different interventions.
DATA COLLECTION AND ANALYSIS
We used standard methods recommended by Cochrane. Subgroup analyses were possible for supervised compared to unsupervised pulmonary rehabilitation programmes in clinically-stable COPD for a range of physical activity outcomes. Secondary outcomes were health-related quality of life, exercise capacity, adverse events and adherence. Insufficient data were available to perform prespecified subgroup analyses by duration of intervention or disease severity. We undertook sensitivity analyses by removing studies that were at high or unclear risk of bias for the domains of blinding and incomplete outcome data.
MAIN RESULTS
We included 76 studies with 8018 participants. Most studies were funded by government bodies, although some were sponsored by equipment or drug manufacturers. Only 38 studies had physical activity as a primary outcome. A diverse range of interventions have been assessed, primarily in single studies, but improvements have not been systematically demonstrated following any particular interventions. Where improvements were demonstrated, results were confined to single studies, or data for maintained improvement were not provided. Step count was the most frequently reported outcome, but it was commonly assessed using devices with documented inaccuracy for this variable. Compared to no intervention, the mean difference (MD) in time in moderate- to vigorous-intensity physical activity (MVPA) following pulmonary rehabilitation was four minutes per day (95% confidence interval (CI) -2 to 9; 3 studies, 190 participants; low-certainty evidence). An improvement was demonstrated following high-intensity interval exercise training (6 minutes per day, 95% CI 4 to 8; 2 studies, 275 participants; moderate-certainty evidence). One study demonstrated an improvement following six months of physical activity counselling (MD 11 minutes per day, 95% CI 7 to 15; 1 study, 280 participants; moderate-certainty evidence), but we found mixed results for the addition of physical activity counselling to pulmonary rehabilitation. There was an improvement following three to four weeks of pharmacological treatment with long-acting muscarinic antagonist and long-acting beta-agonist (LAMA/LABA) compared to placebo (MD 10 minutes per day, 95% CI 4 to 15; 2 studies, 423 participants; high-certainty evidence). These interventions also demonstrated improvements in other measures of physical activity. Other interventions included self-management strategies, nutritional supplementation, supplemental oxygen, endobronchial valve surgery, non-invasive ventilation, neuromuscular electrical stimulation and inspiratory muscle training.
AUTHORS' CONCLUSIONS
A diverse range of interventions have been assessed, primarily in single studies. Improvements in physical activity have not been systematically demonstrated following any particular intervention. There was limited evidence for improvement in physical activity with strategies including exercise training, physical activity counselling and pharmacological management. The optimal timing, components, duration and models for interventions are still unclear. Assessment of quality was limited by a lack of methodological detail. There was scant evidence for a continued effect over time following completion of interventions, a likely requirement for meaningful health benefits for people with COPD.
Topics: Exercise; Humans; Pulmonary Disease, Chronic Obstructive; Randomized Controlled Trials as Topic; Telerehabilitation
PubMed: 32297320
DOI: 10.1002/14651858.CD012626.pub2 -
Monaldi Archives For Chest Disease =... Feb 2020To date treatment protocols in Respiratory and or Internal departments across Italy for treatment of chronic obstructive pulmonary disease (COPD) patients at hospital...
To date treatment protocols in Respiratory and or Internal departments across Italy for treatment of chronic obstructive pulmonary disease (COPD) patients at hospital admission with relapse due to exacerbation do not find adequate support in current guidelines. Here we describe the results of a recent clinical audit, including a systematic review of practices reported in literature and an open discussion comparing these to current real-life procedures. The process was dived into two 8-hour-audits 3 months apart in order to allow work on the field in between meeting and involved 13 participants (3 nurses, 1 physiotherapist, 2 internists and 7 pulmonologists). This document reports the opinions of the experts and their consensus, leading to a bundle of multidisciplinary statements on the use of inhaled drugs for hospitalized COPD patients. Recommendations and topics addressed include: i) monitoring and diagnosis during the first 24 h after admission; ii) treatment algorithm and options (i.e., short and long acting bronchodilators); iii) bronchodilator dosages when switching device or using spacer; iv) flow measurement systems for shifting to LABA+LAMA within 48 h; v) when nebulizers are recommended; vi) use of SMI to deliver LABA+LAMA when patient needs SABA <3 times/day independently from flow limitation; vii) use of DPI and pre-dosed MDI to deliver LABA+LAMA or TRIPLE when patient needs SABA <3 times/day, with inspiratory flow > 30 litres/min; viii) contraindication to use DPI; ix) continuation of LABA-LAMA when patient is already on therapy; x) possible LABA-LAMA dosage increase; xi) use of SABA and/or SAMA in addition to LABA+LABA; xii) use of SABA+SAMA restricted to real need; xiii) reconciliation of drugs in presence of comorbidities; xiv) check of knowledge and skills on inhalation therapy; xv) discharge bundle; xvi) use of MDI and SMI in tracheostomized patients in spontaneous and ventilated breathing.
Topics: Administration, Inhalation; Adrenergic beta-Agonists; Aged, 80 and over; Bronchodilator Agents; Clinical Audit; Disease Progression; Drug Therapy, Combination; Hospitalization; Humans; Italy; Muscarinic Antagonists; Nebulizers and Vaporizers; Patient Care Team; Pulmonary Disease, Chronic Obstructive
PubMed: 32072800
DOI: 10.4081/monaldi.2020.1176 -
The Cochrane Database of Systematic... Jan 2020Nearsightedness (myopia) causes blurry vision when one is looking at distant objects. Interventions to slow the progression of myopia in children include multifocal... (Meta-Analysis)
Meta-Analysis
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.
Topics: Atropine; Child; Contact Lenses; Cyclopentolate; Humans; Muscarinic Antagonists; Myopia, Degenerative; Ophthalmic Solutions; Pirenzepine; Randomized Controlled Trials as Topic
PubMed: 31930781
DOI: 10.1002/14651858.CD004916.pub4