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JAMA Ophthalmology Oct 2023The global prevalence of myopia is predicted to approach 50% by 2050, increasing the risk of visual impairment later in life. No pharmacologic therapy is approved for...
IMPORTANCE
The global prevalence of myopia is predicted to approach 50% by 2050, increasing the risk of visual impairment later in life. No pharmacologic therapy is approved for treating childhood myopia progression.
OBJECTIVE
To assess the safety and efficacy of NVK002 (Vyluma), a novel, preservative-free, 0.01% and 0.02% low-dose atropine formulation for treating myopia progression.
DESIGN, SETTING, AND PARTICIPANTS
This was a double-masked, placebo-controlled, parallel-group, randomized phase 3 clinical trial conducted from November 20, 2017, through August 22, 2022, of placebo vs low-dose atropine, 0.01% and 0.02% (2:2:3 ratio). Participants were recruited from 26 clinical sites in North America and 5 countries in Europe. Enrolled participants were 3 to 16 years of age with -0.50 diopter (D) to -6.00 D spherical equivalent refractive error (SER) and no worse than -1.50 D astigmatism.
INTERVENTIONS
Once-daily placebo, low-dose atropine, 0.01%, or low-dose atropine, 0.02%, eye drops for 36 months.
MAIN OUTCOMES AND MEASURES
The primary, prespecified end point was the proportion of participants' eyes responding to 0.02% atropine vs placebo therapy (<0.50 D myopia progression at 36 months [responder analysis]). Secondary efficacy end points included responder analysis for atropine, 0.01%, and mean change from baseline in SER and axial length at month 36 in a modified intention-to-treat population (mITT; participants 6-10 years of age at baseline). Safety measurements for treated participants (3-16 years of age) were reported.
RESULTS
A total of 576 participants were randomly assigned to treatment groups. Of these, 573 participants (99.5%; mean [SD] age, 8.9 [2.0] years; 315 female [54.7%]) received trial treatment (3 participants who were randomized did not receive trial drug) and were included in the safety set. The 489 participants (84.9%) who were 6 to 10 years of age at randomization composed the mITT set. At month 36, compared with placebo, low-dose atropine, 0.02%, did not significantly increase the responder proportion (odds ratio [OR], 1.77; 95% CI, 0.50-6.26; P = .37) or slow mean SER progression (least squares mean [LSM] difference, 0.10 D; 95% CI, -0.02 D to 0.22 D; P = .10) but did slow mean axial elongation (LSM difference, -0.08 mm; 95% CI, -0.13 mm to -0.02 mm; P = .005); however, at month 36, compared with placebo, low-dose atropine, 0.01%, significantly increased the responder proportion (OR, 4.54; 95% CI, 1.15-17.97; P = .03), slowed mean SER progression (LSM difference, 0.24 D; 95% CI, 0.11 D-0.37 D; P < .001), and slowed axial elongation (LSM difference, -0.13 mm; 95% CI, -0.19 mm to -0.07 mm; P < .001). There were no serious ocular adverse events and few serious nonocular events; none was judged as associated with atropine.
CONCLUSIONS AND RELEVANCE
This randomized clinical trial found that 0.02% atropine did not significantly increase the proportion of participants' eyes responding to therapy but suggested efficacy for 0.01% atropine across all 3 main end points compared with placebo. The efficacy and safety observed suggest that low-dose atropine may provide a treatment option for childhood myopia progression.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT03350620.
PubMed: 37261839
DOI: 10.1001/jamaophthalmol.2023.2097 -
Circulation Oct 2023In this focused update, the American Heart Association provides updated guidance for resuscitation of patients with cardiac arrest, respiratory arrest, and refractory... (Review)
Review
2023 American Heart Association Focused Update on the Management of Patients With Cardiac Arrest or Life-Threatening Toxicity Due to Poisoning: An Update to the American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care.
In this focused update, the American Heart Association provides updated guidance for resuscitation of patients with cardiac arrest, respiratory arrest, and refractory shock due to poisoning. Based on structured evidence reviews, guidelines are provided for the treatment of critical poisoning from benzodiazepines, β-adrenergic receptor antagonists (also known as β-blockers), L-type calcium channel antagonists (commonly called calcium channel blockers), cocaine, cyanide, digoxin and related cardiac glycosides, local anesthetics, methemoglobinemia, opioids, organophosphates and carbamates, sodium channel antagonists (also called sodium channel blockers), and sympathomimetics. Recommendations are also provided for the use of venoarterial extracorporeal membrane oxygenation. These guidelines discuss the role of atropine, benzodiazepines, calcium, digoxin-specific immune antibody fragments, electrical pacing, flumazenil, glucagon, hemodialysis, hydroxocobalamin, hyperbaric oxygen, insulin, intravenous lipid emulsion, lidocaine, methylene blue, naloxone, pralidoxime, sodium bicarbonate, sodium nitrite, sodium thiosulfate, vasodilators, and vasopressors for the management of specific critical poisonings.
Topics: Humans; Adrenergic beta-Antagonists; American Heart Association; Benzodiazepines; Cardiopulmonary Resuscitation; Digoxin; Heart Arrest; United States
PubMed: 37721023
DOI: 10.1161/CIR.0000000000001161 -
Frontiers in Public Health 2023Myopia has significantly risen in East and Southeast Asia, and the pathological outcomes of this condition, such as myopic maculopathy and optic neuropathy linked to... (Review)
Review
Myopia has significantly risen in East and Southeast Asia, and the pathological outcomes of this condition, such as myopic maculopathy and optic neuropathy linked to high myopia, have emerged as leading causes of irreversible vision loss. Addressing this issue requires strategies to reduce myopia prevalence and prevent progression to high myopia. Encouraging outdoor activities for schoolchildren and reducing near-work and screen time can effectively prevent myopia development, offering a safe intervention that promotes healthier habits. Several clinical approaches can be employed to decelerate myopia progression, such as administering low-dose atropine eye drops (0.05%), utilizing orthokeratology lenses, implementing soft contact lenses equipped with myopia control features, and incorporating spectacle lenses with aspherical lenslets. When choosing an appropriate strategy, factors such as age, ethnicity, and the rate of myopia progression should be considered. However, some treatments may encounter obstacles such as adverse side effects, high costs, complex procedures, or limited effectiveness. Presently, low-dose atropine (0.05%), soft contact lenses with myopia control features, and orthokeratology lenses appear as promising options for managing myopia. The measures mentioned above are not necessarily mutually exclusive, and researchers are increasingly exploring their combined effects. By advocating for a personalized approach based on individual risk factors and the unique needs of each child, this review aims to contribute to the development of targeted and effective myopia prevention strategies, thereby minimizing the impact of myopia and its related complications among school-aged children in affected regions.
Topics: Humans; Child; Atropine; Ethnicity; Myopia; Research Personnel
PubMed: 37655278
DOI: 10.3389/fpubh.2023.1226438 -
JAMA Network Open Nov 2023Several interventions exist for treating myopia progression in children. While these interventions' efficacy has been studied, their cost-effectiveness remains unknown...
IMPORTANCE
Several interventions exist for treating myopia progression in children. While these interventions' efficacy has been studied, their cost-effectiveness remains unknown and has not been compared.
OBJECTIVE
To determine cost-effective options for controlling myopia progression in children.
DESIGN, SETTING, AND PARTICIPANTS
In this cost-effectiveness analysis, a Markov model was designed to compare the cost-effectiveness of interventions for controlling myopia progression over 5 years from a societal perspective in a simulated hypothetical cohort of patients aged 10 years with myopia. Myopia interventions considered included atropine eye drops, 0.05% and 0.01%, defocus incorporated multiple segment spectacles, outdoor activity, soft contact lenses (daily disposable and multifocal), rigid gas-permeable contact lenses, progressive addition lenses, bifocal spectacle lenses, orthokeratology, highly aspherical lenslets (HALs), and red light therapy; all interventions were compared with single-vision lenses. Deterministic and probabilistic sensitivity analysis determined the association of model uncertainties with the cost-effectiveness. Costs were obtained from the charges of the Hospital Authority of Hong Kong and The Chinese University of Hong Kong Eye Center.
MAIN OUTCOME AND MEASURES
The mean costs (in US dollars) per child included the cost of hospital visits, medications, and optical lenses. The outcomes of effectiveness were the annual spherical equivalent refraction (SER) and axial length (AL) reductions. Incremental cost-effectiveness ratios (ICERs) were calculated for each strategy relative to single-vision lenses over a time horizon of 5 years.
RESULTS
Outdoor activity, atropine (0.05%), red light therapy, HALs, and orthokeratology were cost-effective. The ICER of atropine, 0.05%, was US $220/SER reduction; red light therapy, US $846/SER reduction; and HALs, US $448/SER reduction. Outdoor activity yielded a savings of US $5/SER reduction and US $8/AL reduction. Orthokeratology resulted in an ICER of US $2376/AL reduction.
CONCLUSIONS AND RELEVANCE
These findings suggest that atropine eye drops, 0.05%, and outdoor activity are cost-effective for controlling myopia progression in children. Though more expensive, red light therapy, HALs, and orthokeratology may also be cost-effective. The use of these interventions may help to control myopia in a cost-effective way.
Topics: Humans; Child; Cost-Effectiveness Analysis; Myopia; Refraction, Ocular; Atropine; Ophthalmic Solutions
PubMed: 37917061
DOI: 10.1001/jamanetworkopen.2023.40986