IMPORTANCE: Early onset of myopia is associated with high myopia later in life, and myopia is irreversible once developed. OBJECTIVE: To evaluate the efficacy of low-concentration atropine eyedrops ...at 0.05% and 0.01% concentration for delaying the onset of myopia. DESIGN, SETTING, AND PARTICIPANTS: This randomized, placebo-controlled, double-masked trial conducted at the Chinese University of Hong Kong Eye Centre enrolled 474 nonmyopic children aged 4 through 9 years with cycloplegic spherical equivalent between +1.00 D to 0.00 D and astigmatism less than −1.00 D. The first recruited participant started treatment on July 11, 2017, and the last participant was enrolled on June 4, 2020; the date of the final follow-up session was June 4, 2022. INTERVENTIONS: Participants were assigned at random to the 0.05% atropine (n = 160), 0.01% atropine (n = 159), and placebo (n = 155) groups and had eyedrops applied once nightly in both eyes over 2 years. MAIN OUTCOMES AND MEASURES: The primary outcomes were the 2-year cumulative incidence rate of myopia (cycloplegic spherical equivalent of at least −0.50 D in either eye) and the percentage of participants with fast myopic shift (spherical equivalent myopic shift of at least 1.00 D). RESULTS: Of the 474 randomized patients (mean age, 6.8 years; 50% female), 353 (74.5%) completed the trial. The 2-year cumulative incidence of myopia in the 0.05% atropine, 0.01% atropine, and placebo groups were 28.4% (33/116), 45.9% (56/122), and 53.0% (61/115), respectively, and the percentages of participants with fast myopic shift at 2 years were 25.0%, 45.1%, and 53.9%. Compared with the placebo group, the 0.05% atropine group had significantly lower 2-year cumulative myopia incidence (difference, 24.6% 95% CI, 12.0%-36.4%) and percentage of patients with fast myopic shift (difference, 28.9% 95% CI, 16.5%-40.5%). Compared with the 0.01% atropine group, the 0.05% atropine group had significantly lower 2-year cumulative myopia incidence (difference, 17.5% 95% CI, 5.2%-29.2%) and percentage of patients with fast myopic shift (difference, 20.1% 95% CI, 8.0%-31.6%). The 0.01% atropine and placebo groups were not significantly different in 2-year cumulative myopia incidence or percentage of patients with fast myopic shift. Photophobia was the most common adverse event and was reported by 12.9% of participants in the 0.05% atropine group, 18.9% in the 0.01% atropine group, and 12.2% in the placebo group in the second year. CONCLUSIONS AND RELEVANCE: Among children aged 4 to 9 years without myopia, nightly use of 0.05% atropine eyedrops compared with placebo resulted in a significantly lower incidence of myopia and lower percentage of participants with fast myopic shift at 2 years. There was no significant difference between 0.01% atropine and placebo. Further research is needed to replicate the findings, to understand whether this represents a delay or prevention of myopia, and to assess longer-term safety. TRIAL REGISTRATION: Chinese Clinical Trial Registry: ChiCTR-IPR-15006883
Zhang et al respond to comments by Dr Tsuda and colleagues about their article on the use of low-concentration atropine eyedrops for myopia in children. They state that they appreciate the ...opportunity to address the comments by Dr Tsuda and colleagues about their article. First, they acknowledge that the participant dropout rate in our study was higher than anticipated. However, there were no significant differences in terms of demographics and baseline parameters between participants who attended follow-up and those who dropped out (eTable 2 in Supplement 1 of the article). The overall dropout rates were also similar among the 3 groups. Importantly, the association between the baseline characteristics of the participants and the dropouts was evaluated and the results showed that dropouts were not associated with treatment groups.
Update of treatment for myopia Bremond‐Gignac, Dominique
Acta ophthalmologica,
January 2024, 2024-01-00, 20240101, Letnik:
102, Številka:
S279
Journal Article
Recenzirano
Odprti dostop
The use of myopia control devices is essential due to increased frequency of myopic children. Different solutions can be proposed in evolutive forms. Ocular check‐up and discussion with parents and ...their child allowed to adapt the best system to control myopia evolution. Optical correction are based on defocus system to control myopia. Defocus glasses with different systems (DIMS, HALT, …), defocus soft contact lenses with systems (dual concentric ring, EDOF), and orthokeratology are proposed. Atropine low dose is also a very effective treatment when duration is at least 2 years. Different systems to treat myopia must be customized to children and parents needs.
Aims/Purpose: Assessing axial eye growth is a key component in myopia management; however, access to biometry is limited in primary eye care settings. This study evaluated choroidal thickness, ...compared to spherical equivalent refraction, as a potential biomarker of axial elongation.
Methods: The Myopia Outcome Study of Atropine in Children (MOSAIC) is a double‐blind, randomized controlled trial of 0.01% atropine eye drops. Irish myopic participants aged 6–16 years used either 0.01% atropine or placebo eye drops nightly for 2 years. Spherical equivalent refraction (SER) was measured by cycloplegic autorefraction, axial length (AL) by partial coherence interferometry and choroidal thickness (ChT) by Swept Source‐OCT. The respective 12‐month changes in both eyes were included in mixed linear regression analysis, while controlling for treatment group and within‐subject correlation. ROC analysis was conducted to assess the ability of ChT and/or SER to identify eyes in the top 25% (fast progressors) of AL change.
Results: Of the 250 participants enrolled in MOSAIC (mean age 11.8 years, 62% female), 217 (87%) completed the 12‐month visit. Mean 12‐month change in AL, ChT and SER were 0.268 ± 0.19 mm, −3.62 ± 33.3 um and −0.437 ± 0.346 DS respectively. Analysis revealed a significant association between change in ChT and AL (−0.01 ± 0.002 mm per 10 μm; p < 0.001) and change in SER and AL (−0.28 ± 0.02 mm per 1D; p < 0.001). When both SER and ChT were combined in a single model, a 1D myopic change in SER and a 10um decrease in ChT were associated with a 0.27 mm (p < 0.001) and 0.007 mm increase in AL (p = 0.002), respectively. ROC analysis revealed that change in ChT was a stronger predictor of fast AL progression (AUC = 0.77) compared to SER change (AUC = 0.72), with the combined model performing better than either variable alone (AUC = 0.80).
Conclusions: ChT change was significantly associated with AL change over 12 months and better than SER alone at identifying fast AL progressors, with a combined SER and ChT model achieving the best results.
Myopia is a global problem that is increasing at an epidemic rate in the world. Although the refractive error can be corrected easily, myopes, particularly those with high myopia, are susceptible to ...potentially blinding eye diseases later in life. Despite a plethora of myopia research, the molecular/cellular mechanisms underlying the development of myopia are not well understood, preventing the search for the most effective pharmacological control. Consequently, several approaches to slowing down myopia progression in the actively growing eyes of children have been underway. So far, atropine, an anticholinergic blocking agent, has been most effective and is used by clinicians in off-label ways for myopia control. Although the exact mechanisms of its action remain elusive and debatable, atropine encompasses a complex interplay with receptors on different ocular tissues at multiple levels and, hence, can be categorized as a shotgun approach to myopia treatment. This review will provide a brief overview of the biological mechanisms implicated in mediating the effects of atropine in myopia control.
The high number of annual fatalities following suicidal poisoning by organophosphorus (OP) pesticides and the recent homicidal use of the chemical warfare nerve agent sarin against civilian ...population in Syria underlines the continuous threat by these highly toxic agents. The need for an effective treatment of OP poisoning resulted in the implementation of a combination therapy with the muscarinic receptor antagonist atropine and an oxime for the reactivation of OP-inhibited acetylcholinesterase (AChE). Since the invention of the first clinically used oxime pralidoxime (2-PAM) in the 1950s ongoing research attempted to identify more effective oximes. In fact, several thousand oximes were synthesized in the past six decades. These include charged and non-charged compounds, mono- and bispyridinium oximes, asymmetric oximes, oximes with different substitutes and more recently non-oxime reactivators. Multiple in vitro and in vivo studies investigated the potential of oximes to reactivate OP-inhibited AChE and to reverse OP-induced cholinergic signs. Depending on the experimental model, the investigated species and the tested OP largely variable results were obtained by different laboratories. These findings and the inconsistent effectiveness of oximes in the treatment of OP-pesticide poisoned patients led to a continuous discussion on the value of oximes. In order to provide a forward-looking evaluation of the significance of oximes in OP poisoning multiple aspects, including intrinsic toxicity, in vitro reactivation potency, efficacy and pharmacokinetics, as well as the impact of the causative OP have to be considered. The different influencing factors in order to define the benefit and limitations of oximes in OP poisoning will be discussed.
•Research on effective oximes against organophosphate poisoning continues since more than six decades.•The value of oximes in organophosphate poisoning is still under debate.•A proper evaluation of the potential and limitations of oximes is urgently needed.•Factors for limiting the effectiveness of oximes are discussed.
Comparative efficacy and safety of different concentrations of atropine for myopia control.
Atropine is known to be an effective intervention to delay myopia progression. Nonetheless, no ...well-supported evidence exists yet to rank the clinical outcomes of various concentrations of atropine.
We searched PubMed, EMBASE, Cochrane Central Register of Controlled Trials, the World Health Organization International Clinical Trials Registry Platform, and ClinicalTrials.gov on April 14, 2021. We selected studies involving atropine treatment of at least 1 year’s duration for myopia control in children. We performed a network meta-analysis (NMA) of randomized controlled trials (RCTs) and compared 8 atropine concentrations (1% to 0.01%). We ranked the atropine concentrations for the corresponding outcomes by P score (estimate of probability of being best treatment). Our primary outcomes were mean annual changes in refraction (diopters/year) and axial length (AXL; millimeters/year). We extracted data on the proportion of eyes showing myopia progression and safety outcomes (photopic and mesopic pupil diameter, accommodation amplitude, and distance and near best-corrected visual acuity BCVA).
Thirty pairwise comparisons from 16 RCTs (3272 participants) were obtained. Our NMA ranked the 1%, 0.5%, and 0.05% atropine concentrations as the 3 most beneficial for myopia control, as assessed for both primary outcomes: 1% atropine (mean differences compared with control: refraction, 0.81 95% confidence interval (CI), 0.58–1.04; AXL, –0.35 –0.46 to –0.25); 0.5% atropine (mean differences compared with control: refraction, 0.70 95% CI, 0.40–1.00; AXL, –0.23 –0.38 to –0.07); 0.05% atropine (mean differences compared with control: refraction, 0.62 95% CI, 0.17–1.07; AXL, –0.25 –0.44 to –0.06). In terms of myopia control as assessed by relative risk (RR) for overall myopia progression, 0.05% was ranked as the most beneficial concentration (RR, 0.39 95% CI, 0.27–0.57). The risk for adverse effects tended to rise as the atropine concentration was increased, although this tendency was not evident for distance BCVA. No valid network was formed for near BCVA.
The ranking probability for efficacy was not proportional to dose (i.e., 0.05% atropine was comparable with that of high-dose atropine 1% and 0.5%), although those for pupil size and accommodation amplitude were dose related.
The prevalence of myopia is increasing globally. Complications of myopia are associated with huge economic and social costs. It is believed that high myopia in adulthood can be traced back to school ...age onset myopia. Therefore, it is crucial and urgent to implement effective measures of myopia control, which may include preventing myopia onset as well as retarding myopia progression in school age children. The mechanism of myopia is still poorly understood. There are some evidences to suggest excessive expansion of Bruch's membrane, possibly in response to peripheral hyperopic defocus, and it may be one of the mechanisms leading to the uncontrolled axial elongation of the globe. Atropine is currently the most effective therapy for myopia control. Recent clinical trials demonstrated low-dose atropine eye drops such as 0.01% resulted in retardation of myopia progression, with significantly less side effects compared to higher concentration preparation. However, there remain a proportion of patients who are poor responders, in whom the optimal management remains unclear. Proposed strategies include stepwise increase of atropine dosing, and a combination of low-dose atropine with increase outdoor time. This review will focus on the current understanding of epidemiology, pathophysiology in myopia and highlight recent clinical trials using atropine in the school-aged children, as well as the treatment strategy in clinical implementation in hyperopic, pre-myopic and myopic children.
To examine the changes in choroidal thickness (ChT) after 6 months of 1% or 0.01% atropine treatment and the independent factors associated with eye elongation.
A total of 207 myopic children aged 6 ...to 12 years were recruited and randomly assigned to groups A and B in a ratio of 1:1. Participants in group A received 1% atropine once a day for 1 week, and then once a week for 23 weeks. Participants in group B received 0.01% atropine once a day for 6 months. ChT and internal axial length (IAL) were measured at baseline, 1 week, 3 months, and 6 months.
In group A, the ChT significantly increased after a 1-week loading dose of 1% atropine (26 ± 14 µm; P < 0.001) and the magnitude of increase stabilized throughout the following weekly treatment. The internal axial length did not significantly change at the 6-month visit (-0.01 ± 0.11 mm; P = 0.74). In contrast, a decreased ChT (-5 ± 17 µm; P < 0.001) and pronounced eye elongation (0.19 ± 0.12 mm; P < 0.001) were observed in group B after 6 months. Multivariable regression analysis showed that less increase in ChT at the 1-week visit (P = 0.03), younger age (P < 0.001), and presence of peripapillary atrophy (P = 0.001) were significantly associated with greater internal axial length increase over 6 months in group A.
One percent atropine could increase the ChT, whereas 0.01% atropine caused a decrease in ChT after 6 months of treatment. For participants receiving 1% atropine, the short-term increase in ChT was negatively associated with long-term eye elongation. Younger age and the presence of peripapillary atrophy were found to be risk factors for greater eye elongation.
Background
Dobutamine‐atropine stress echocardiography (DSE) has lower sensitivity in patients with advanced liver disease (ALD) due to vasodilation.
Hypothesis
Dopamine‐atropine stress ...echocardiography (DopSE) may be an alternative to DSE in ALD patients by improving the blood pressure response to stress.
Methods
The safety and tolerability of DSE and DopSE were compared in 10 volunteers. The safety, adverse effects, and efficacy of DopSE were then assessed in 105 patients, 98 of whom had ALD. Dopamine was infused in stepwise fashion from 5 µg/kg/min to a peak dose of 40 µg/kg/min. Atropine was given before and in early stages of dopamine infusion up to cumulative dose of 1.5 mg. The hemodynamic responses of 98 ALD patients were compared with 102 patients with ALD who underwent standard DSE.
Results
In normal volunteers, systolic BP increased more with DopSE compared to DSE (61 ± 19 mm Hg vs 39 ± 15 mm Hg, P = .008). In 105 patients who underwent DopSE, none had adverse effects that required early stress termination. In the groups with ALD, the systolic BP increase (38 ± 28 mm Hg vs 12 ± 27 mm Hg, P < .001) and peak rate pressure product (RPP) (22 861 ± 5289 vs 17 211 ± 3848, P = <.001) were both higher in those undergoing DopSE versus DSE. The sensitivity and specificity of DopSE were 45% and 88%, respectively for coronary disease (≥70% stenosis) in 37 patients who had angiography.
Conclusions
Dopamine‐atropine stress echocardiography appears to be a safe stress modality and provides greater increases in RPP in patients with ALD compared to DSE.
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