Hypertensive emergency secondary to atropine / Emergencia hipertensiva secundaria a atropina

Atropine, a competitive antagonist of acetylcholine muscarinic receptors, is commonly used to treat severe bradycardia by blocking parasympathetic activity. We present a rare case of hypertensive emergency following atropine administration, with only one previous report in the literature. A 78-year-old woman with essential hypertension and hypercholesterolemia was admitted to the cardiac intensive care unit for non-ST segment elevation myocardial infarction. During coronary angiography, an occlusion of the right coronary artery was identified. While removing the diagnostic catheter through the right radial artery, the patient experienced intense pain and discomfort, accompanied by a vasovagal reflex characterized by bradycardia and hypotension. Intravenous atropine (0.5mg) was administered, leading to a rapid rise in heart rate with frequent ventricular ectopy. Subsequently, a progressive and exaggerated elevation in arterial blood pressure occurred, peaking at 294/121mmHg approximately 10min after atropine administration. The patient developed hypertensive acute pulmonary edema, successfully treated with intravenous nitroglycerine (10mg) and furosemide (60mg). Blood pressure normalized after approximately 14min. The exact mechanism of atropine-induced hypertensive emergency remains unknown. While hypertensive emergencies with atropine are exceedingly rare, healthcare professionals should be aware of this potential effect and be prepared for prompt intervention.(AU)

La atropina, un antagonista competitivo de los receptores muscarínicos de acetilcolina, se utiliza comúnmente para tratar la bradicardia severa al bloquear la actividad parasimpática. Presentamos un caso raro de emergencia hipertensiva después de la administración de atropina, con solo un informe previo en la literatura. Una mujer de 78 años con hipertensión esencial e hipercolesterolemia fue ingresada en la unidad de cuidados intensivos cardíacos por infarto agudo de miocardio sin elevación del segmento ST. Durante la angiografía coronaria, se identificó una oclusión de la arteria coronaria derecha. Mientras se retiraba el catéter diagnóstico a través de la arteria radial derecha, la paciente experimentó un intenso dolor y malestar, acompañado de un reflejo vasovagal caracterizado por bradicardia e hipotensión. Se administró atropina intravenosa (0,5 mg), lo que provocó un rápido aumento de la frecuencia cardíaca con frecuente ectopia ventricular. Posteriormente, ocurrió una elevación progresiva y exagerada de la presión arterial, alcanzando un máximo de 294/121 mmHg aproximadamente 10 minutos después de la administración de atropina. La paciente desarrolló edema pulmonar agudo hipertensivo, tratado con éxito con nitroglicerina intravenosa (10 mg) y furosemida (60 mg). La presión arterial se normalizó después de aproximadamente 14 minutos. El mecanismo exacto de la emergencia hipertensiva inducida por atropina sigue siendo desconocido. Aunque las emergencias hipertensivas con atropina son excepcionalmente raras, los profesionales de la salud deben estar al tanto de este efecto potencial y estar preparados para intervenir rápidamente.(AU)

Topical Atropine for Childhood Myopia Control: The Atropine Treatment Long-Term Assessment Study.

Importance: Clinical trial results of topical atropine eye drops for childhood myopia control have shown inconsistent outcomes across short-term studies, with little long-term safety or other outcomes reported. Objective: To report the long-term safety and outcomes of topical atropine for childhood myopia control. Design, Setting, and Participants: This prospective, double-masked observational study of the Atropine for the Treatment of Myopia (ATOM) 1 and ATOM2 randomized clinical trials took place at 2 single centers and included adults reviewed in 2021 through 2022 from the ATOM1 study (atropine 1% vs placebo; 1999 through 2003) and the ATOM2 study (atropine 0.01% vs 0.1% vs 0.5%; 2006 through 2012). Main Outcome Measures: Change in cycloplegic spherical equivalent (SE) with axial length (AL); incidence of ocular complications. Results: Among the original 400 participants in each original cohort, the study team evaluated 71 of 400 ATOM1 adult participants (17.8% of original cohort; study age, mean [SD] 30.5 [1.2] years; 40.6% female) and 158 of 400 ATOM2 adult participants (39.5% of original cohort; study age, mean [SD], 24.5 [1.5] years; 42.9% female) whose baseline characteristics (SE and AL) were representative of the original cohort. In this study, evaluating ATOM1 participants, the mean (SD) SE and AL were -5.20 (2.46) diopters (D), 25.87 (1.23) mm and -6.00 (1.63) D, 25.90 (1.21) mm in the 1% atropine-treated and placebo groups, respectively (difference of SE, 0.80 D; 95% CI, -0.25 to 1.85 D; P = .13; difference of AL, -0.03 mm; 95% CI, -0.65 to 0.58 mm; P = .92). In ATOM2 participants, the mean (SD) SE and AL was -6.40 (2.21) D; 26.25 (1.34) mm; -6.81 (1.92) D, 26.28 (0.99) mm; and -7.19 (2.87) D, 26.31 (1.31) mm in the 0.01%, 0.1%, and 0.5% atropine groups, respectively. There was no difference in the 20-year incidence of cataract/lens opacities, myopic macular degeneration, or parapapillary atrophy (ß/γ zone) comparing the 1% atropine-treated group vs the placebo group. Conclusions and Relevance: Among approximately one-quarter of the original participants, use of short-term topical atropine eye drops ranging from 0.01% to 1.0% for a duration of 2 to 4 years during childhood was not associated with differences in final refractive errors 10 to 20 years after treatment. There was no increased incidence of treatment or myopia-related ocular complications in the 1% atropine-treated group vs the placebo group. These findings may affect the design of future clinical trials, as further studies are required to investigate the duration and concentration of atropine for childhood myopia control.

Ortoqueratología vs ortoqueratología combinada con atropina para el control de miopía en niños: revisión sistemática / Orthokeratology vs. orthokeratology combined with atropine for the control of myopia in children: Systematic review

El propósito de esta investigación es determinar la eficacia de la ortoqueratología (OK) en comparación con la ortoqueratología combinada con atropina (AOK) para el control de la miopía en niños. Se realizó una revisión sistemática que incluyó revisiones sistemáticas con metaanálisis, además de ensayos clínicos aleatorizados y controlados, en las bases de datos PubMed, Web of Science, Scopus, Cochrane Library, ProQuest, Taylor & Francis, Science Direct, y de una búsqueda manual de las revistas Q1-Q4 del Scimago Journal & Country Rank, publicadas en últimos 5 años en idioma inglés y español. Se tomaron en cuenta 18 estudios que cumplieron con los criterios de elegibilidad. Los artículos seleccionados incluyeron 6.866 pacientes para el análisis, en donde se encontró mayor eficacia de la AOK al 0,01% debido a su capacidad de reducir la progresión de miopía y alargamiento axial. En nuestra investigación se determinó que podría existir un efecto aditivo en la combinación de atropina al 0,01% con OK en un periodo de 1 a 2 años de tratamiento en pacientes con miopía leve, sin embargo, se deben realizar más estudios multiétnicos, en donde se considere una correcta evaluación de la progresión de miopía, factores genéticos y ambientales que puedan influir en los resultados (AU)

The purpose of this investigation is to determine the efficacy of orthokeratology (OK) compared to orthokeratology combined with atropine (AOK) for the control of myopia in children. A systematic review that included systematic reviews with meta-analyses, as well as randomized and controlled clinical trials, was carried out in the PubMed, Web of Science, Scopus, Cochrane Library, ProQuest, Taylor & Francis, Science Direct databases, as well as a manual search of the Q1-Q4 journals of the Scimago Journal & Country Rank, published in the last 5 years in English and Spanish. Eighteen studies that met the eligibility criteria were considered. The articles selected included 6866 patients for analysis, where orthokeratology combined with 0.01% atropine was found to be more effective due to its ability to reduce the progression of myopia and axial elongation. In our investigation, it was determined that there could be an additive effect in the combination of 0.01% atropine with orthokeratology in a period of 1–2 years of treatment in patients with mild myopia; however, more multiethnic studies should be carried out, in where a correct evaluation of the progression of myopia, genetic and environmental factors that may influence the results is considered (AU)

Low-Dose 0.01% Atropine Eye Drops vs Placebo for Myopia Control: A Randomized Clinical Trial.

Importance: Controlling myopia progression is of interest worldwide. Low-dose atropine eye drops have slowed progression in children in East Asia. Objective: To compare atropine, 0.01%, eye drops with placebo for slowing myopia progression in US children. Design, Setting, and Participants: This was a randomized placebo-controlled, double-masked, clinical trial conducted from June 2018 to September 2022. Children aged 5 to 12 years were recruited from 12 community- and institution-based practices in the US. Participating children had low to moderate bilateral myopia (-1.00 diopters [D] to -6.00 D spherical equivalent refractive error [SER]). Intervention: Eligible children were randomly assigned 2:1 to 1 eye drop of atropine, 0.01%, nightly or 1 drop of placebo. Treatment was for 24 months followed by 6 months of observation. Main Outcome and Measures: Automated cycloplegic refraction was performed by masked examiners. The primary outcome was change in SER (mean of both eyes) from baseline to 24 months (receiving treatment); other outcomes included change in SER from baseline to 30 months (not receiving treatment) and change in axial length at both time points. Differences were calculated as atropine minus placebo. Results: A total of 187 children (mean [SD] age, 10.1 [1.8] years; age range, 5.1-12.9 years; 101 female [54%]; 34 Black [18%], 20 East Asian [11%], 30 Hispanic or Latino [16%], 11 multiracial [6%], 6 West/South Asian [3%], 86 White [46%]) were included in the study. A total of 125 children (67%) received atropine, 0.01%, and 62 children (33%) received placebo. Follow-up was completed at 24 months by 119 of 125 children (95%) in the atropine group and 58 of 62 children (94%) in the placebo group. At 30 months, follow-up was completed by 118 of 125 children (94%) in the atropine group and 57 of 62 children (92%) in the placebo group. At the 24-month primary outcome visit, the adjusted mean (95% CI) change in SER from baseline was -0.82 (-0.96 to -0.68) D and -0.80 (-0.98 to -0.62) D in the atropine and placebo groups, respectively (adjusted difference = -0.02 D; 95% CI, -0.19 to +0.15 D; P = .83). At 30 months (6 months not receiving treatment), the adjusted difference in mean SER change from baseline was -0.04 D (95% CI, -0.25 to +0.17 D). Adjusted mean (95% CI) changes in axial length from baseline to 24 months were 0.44 (0.39-0.50) mm and 0.45 (0.37-0.52) mm in the atropine and placebo groups, respectively (adjusted difference = -0.002 mm; 95% CI, -0.106 to 0.102 mm). Adjusted difference in mean axial elongation from baseline to 30 months was +0.009 mm (95% CI, -0.115 to 0.134 mm). Conclusions and Relevance: In this randomized clinical trial of school-aged children in the US with low to moderate myopia, atropine, 0.01%, eye drops administered nightly when compared with placebo did not slow myopia progression or axial elongation. These results do not support use of atropine, 0.01%, eye drops to slow myopia progression or axial elongation in US children. Trial Registration: ClinicalTrials.gov Identifier: NCT03334253.

Potential Choroidal Mechanisms Underlying Atropine's Antimyopic and Rebound Effects: A Mediation Analysis in a Randomized Clinical Trial.

Purpose: To investigate whether choroidal vascularity participates in high-dose atropine's antimyopia and rebound mechanisms. Methods: A mediation analysis was embedded within a randomized controlled trial. In total, 207 myopic children were assigned randomly to group A/B. Participants in group A received 1% atropine weekly (phase 1) and 0.01% atropine daily (phase 2) for 6 months each. Those in group B received 0.01% atropine daily for 1 year. Four plausible intervention mediators were assessed: total choroidal area (TCA), luminal area (LA), stromal area (SA), and choroidal vascularity index (CVI). Results: In group A, LA, SA, and TCA increased significantly after receiving 1% atropine for 6 months. The increment diminished after tapering to 0.01% atropine. In group B, those parameters remained stable. TCA mediated approximately one-third of 1% atropine's effect on spherical equivalent progression in both phases. In phase 1, the mediation effect of TCA was shared by LA and SA, while only that of LA remained significant in phase 2. No mediation effect of CVI was found. Conclusions: One percent atropine induced choroidal thickening by increasing both LA and SA, while 0.01% atropine had little choroidal response. The choroidal changes following 1% atropine treatment diminished after switching to 0.01% atropine. TCA, but not CVI, partially explains atropine's antimyopic and myopic-rebound mechanisms. SA may serve as a potential biomarker to predict the postrebound treatment efficacy of high-dose atropine. (ClinicalTrials.gov number, NCT03949101.).

Effect of Low-Concentration Atropine Eyedrops vs Placebo on Myopia Incidence in Children: The LAMP2 Randomized Clinical Trial.

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.

Efficacy of 0.01% low dose atropine and its correlation with various factors in myopia control in the Indian population.

We aimed to evaluate the efficacy and safety of low-dose atropine compared to placebo in the Indian population and also to study the impact of various modifiable and non-modifiable factors on myopia progression (MP) and drug efficacy (DE). It was a single-centre prospective placebo-controlled interventional study. 43 participants aged 6-16 years with progressive myopia received 0.01% atropine in the right eyes (treatment) and placebo in the left eyes (control) for 1-year. The main outcome measures were annual MP and axial length elongation (ALE) in treatment and control eyes and their percentage difference between two eyes (drug efficacy). Secondary outcome measures were the occurrence of any adverse events and the correlation of MP, ALE, and DE with various factors. 40 participants (80 eyes) completed the follow-up. After 1-year, MP was 0.25 D (IQR 0.13-0.44) and 0.69 D (IQR 0.50-1.0) (p < 0.001) in treatment and control respectively (63.89% reduction) with respective ALE of 0.14 mm (IQR 0.05-0.35) and 0.32 mm (IQR 0.19-0.46) (p < 0.001) (44.44% reduction). No adverse events were noted. Reduction in MP and ALE was statistically significant in all children irrespective of age-group, baseline MP, family history, screen-time, near and outdoor-time. The strongest determinants of annual MP were age (Treatment: r = - 0.418, p = 0.007; Control: r = - 0.452, p = 0.003) and baseline MP (Treatment: r = 0.64, p = 0.000; Control: r = 0.79, p = 0.000). Screen-time in control eyes was associated with greater ALE (r = 0.620, p = 0.042). DE was higher when outdoor time exceeded 2 h/day (p = 0.035) while the efficacy was lower with prolonged near activities (p = 0.03), baseline fast-progressors (p < 0.05) and history of parental myopia (p < 0.05). 0.01% atropine is effective and safe in retarding MP and ALE in Indian eyes.

Balanced modulation of neuromuscular synaptic transmission via M1 and M2 muscarinic receptors during inhibition of cholinesterases.

Organophosphorus (OP) compounds that inhibit acetylcholinesterase are a common cause of poisoning worldwide, resulting in several hundred thousand deaths each year. The pathways activated during OP compound poisoning via overstimulation of muscarinic acetylcholine receptors (mAChRs) play a decisive role in toxidrome. The antidotal therapy includes atropine, which is a nonspecific blocker of all mAChR subtypes. Atropine is efficient for mitigating depression in respiratory control centers but does not benefit patients with OP-induced skeletal muscle weakness. By using an ex vivo model of OP-induced muscle weakness, we studied the effects of the M1/M4 mAChR antagonist pirenzepine and the M2/M4 mAChR antagonist methoctramine on the force of mouse diaphragm muscle contraction. It was shown that weakness caused by the application of paraoxon can be significantly prevented by methoctramine (1 µM). However, neither pirenzepine (0.1 µM) nor atropine (1 µM) was able to prevent muscle weakness. Moreover, the application of pirenzepine significantly reduced the positive effect of methoctramine. Thus, balanced modulation of neuromuscular synaptic transmission via M1 and M2 mAChRs contributes to paraoxon-induced muscle weakness. It was shown that methoctramine (10 µmol/kg, i.p.) and atropine (50 µmol/kg, i.p.) were equieffective toward increasing the survival of mice poisoned with a 2xLD50 dose of paraoxon.

Loading and Sustained Release of Pralidoxime Chloride from Swellable MIL-88B(Fe) and Its Therapeutic Performance on Mice Poisoned by Neurotoxic Agents.

Maintaining a long-term continuous and stable reactivator blood concentration to treat organophosphorus nerve agent poisoning using acetylcholinesterase (AChE) reactivator pralidoxime chloride (2-PAM) is very important yet difficult. Because the flexible framework of MIL-88B(Fe) nanoparticles (NPs) can swell in polar solvents, pralidoxime chloride (2-PAM) was loaded in MIL-88B(Fe) NPs (size: ca. 500 nm) by stirring and incubation in deionized water to obtain 2-PAM@MIL-88B(Fe), which had a maximum drug loading capacity of 12.6 wt %. The as-prepared composite was characterized by IR, powder X-ray diffraction (P-XRD), scanning electron microscopy (SEM), ζ-potential, Brunauer-Emmett-Teller (BET), and thermogravimetry/differential thermal analysis (TG/DTA). The results showed that under constant conditions, the maximum drug release rates of 2-PAM@MIL-88B(Fe) in absolute ethanol, phosphate-buffered saline (PBS) solution (pH = 7.4), and PBS solution (pH = 4) at 150 h were 51.7, 80.6, and 67.1%, respectively. This was because the composite showed different swelling behaviors in different solvents. In PBS solution with pH = 2, the 2-PAM@MIL-88B(Fe) framework collapsed after 53 h and released 100% of 2-PAM. For mice after intragastric poisoning with sarin (a neurotoxic agent), an atropine-assisted 2-PAM@MIL-88B(Fe) treatment experiment revealed that 2-PAM@MIL-88B(Fe) continuously released 2-PAM for more than 72 h so that poisoned AChE was continuously and steadily reactivated. The reactivation rate of AChE was 56.7% after 72 h. This composite is expected to provide a prolonged, stable therapeutic drug for the mid- and late-stage treatment of neurotoxic agent poisoning.

Efficacy and Safety of 8 Atropine Concentrations for Myopia Control in Children: A Network Meta-Analysis.

TOPIC: Comparative efficacy and safety of different concentrations of atropine for myopia control. CLINICAL RELEVANCE: 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. METHODS: 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]). RESULTS: 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. DISCUSSION: 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.

Three-Year Clinical Trial of Low-Concentration Atropine for Myopia Progression (LAMP) Study: Continued Versus Washout: Phase 3 Report.

PURPOSE: (1) To compare the efficacy of continued and stopping treatment for 0.05%, 0.025%, and 0.01% atropine during the third year. (2) To evaluate the efficacy of continued treatment over 3 years. (3) To investigate the rebound phenomenon and its determinants after cessation of treatment. DESIGN: A randomized, double-masked extended trial. PARTICIPANTS: A total of 350 of 438 children aged 4 to 12 years originally recruited into the Low-Concentration Atropine for Myopia Progression (LAMP) study. METHODS: At the beginning of the third year, children in each group were randomized at a 1:1 ratio to continued treatment and washout subgroups. Cycloplegic spherical equivalent (SE) refraction and axial length (AL) were measured at 4-month intervals. MAIN OUTCOME MEASURES: Changes in SE and AL between groups. RESULTS: A total of 326 children completed 3 years of follow-up. During the third year, SE progression and AL elongation were faster in the washout subgroups than in the continued treatment groups across all concentrations: -0.68 ± 0.49 diopters (D) versus -0.28 ± 0.42 D (P < 0.001) and 0.33 ± 0.17 mm versus 0.17 ± 0.14 mm (P < 0.001) for the 0.05%; -0.57 ± 0.38 D versus -0.35 ± 0.37 D (P = 0.004) and 0.29 ± 0.14 mm versus 0.20 ± 0.15 mm (P = 0.001) for the 0.025%; -0.56 ± 0.40 D versus -0.38 ± 0.49 D (P = 0.04) and 0.29 ± 0.15 mm versus 0.24 ± 0.18 mm (P = 0.13) for the 0.01%. Over the 3-year period, SE progressions were -0.73 ± 1.04 D, -1.31 ± 0.92 D, and -1.60 ± 1.32 D (P = 0.001) for the 0.05%, 0.025%, and 0.01% groups in the continued treatment subgroups, respectively, and -1.15 ± 1.13 D, -1.47 ± 0.77 D, and -1.81 ± 1.10 D (P = 0.03), respectively, in the washout subgroup. The respective AL elongations were 0.50 ± 0.40 mm, 0.74 ± 0.41 mm, and 0.89 ± 0.53 mm (P < 0.001) for the continued treatment subgroups and 0.70 ± 0.47 mm, 0.82 ± 0.37 mm, and 0.98 ± 0.48 mm (P = 0.04) for the washout subgroup. The rebound SE progressions during washout were concentration dependent, but their differences were clinically small (P = 0.15). Older age and lower concentration were associated with smaller rebound effects in both SE progression (P < 0.001) and AL elongation (P < 0.001). CONCLUSIONS: During the third year, continued atropine treatment achieved a better effect across all concentrations compared with the washout regimen. 0.05% atropine remained the optimal concentration over 3 years in Chinese children. The differences in rebound effects were clinically small across all 3 studied atropine concentrations. Stopping treatment at an older age and lower concentration are associated with a smaller rebound.

A multicenter Spanish study of atropine 0.01% in childhood myopia progression.

To evaluate the efficacy and safety of atropine 0.01% eye drops for myopia control in a multicentric pediatric Spanish cohort. An interventional, prospective, multicenter study was designed. Children aged between 6 and 14 years, with myopia between - 2.00 D to - 6.00 D, astigmatism < 1.50 D and documented previous annual progression greater than - 0.5 D (cycloplegic spherical equivalent, SE) were included. Once nightly atropine 0.01% eye drops in each eye were prescribed to all participants for 12 months. Age, gender, ethnicity and iris color were registered. All patients underwent the same follow-up protocol in every center: baseline visit, telephone consultation 2 weeks later and office controls at 4, 8 and 12 months. At each visit, best-corrected visual acuity, and cycloplegic autorefraction were assessed. Axial length (AL), anterior chamber depth and pupil diameter were measured on an IOL Master (Carl Zeiss Meditec, Inc, Dublin, CA). Adverse effects were registered in a specific questionnaire. Mean changes in cycloplegic SE and AL in the 12 months follow-up were analyzed. SE progression during treatment was compared with the SE progression in the year before enrollment for each patient. Correlation between SE and AL, and annual progression distribution were evaluated. Progression risk factors were analyzed by multivariate logistic regression analyses. Of the 105 recruited children, 92 completed the treatment. Mean SE and AL changes were - 0.44 ± 0.41 D and 0.27 ± 0.20 mm respectively. Mean SE progression was lower than the year before treatment (- 0.44 ± 0.41 D versus - 1.01 ± 0.38 D; p < 0.0001). An inverse correlation between SE progression and AL progression (r: - 0.42; p < 0.0001) was found. Fifty-seven patients (62%) had a SE progression less than - 0.50 D. No risk factors associated with progression could be identified in multivariate analyses. Mean pupil diameter increment at 12-months visit was 0.74 ± 1.76 mm. The adverse effects were mild and infrequent, and decreased over the time. Atropine 0.01% is effective and safe for myopia progression control in a multicentric Spanish children cohort. We believe this efficacy might be extensible to the myopic pediatric population from Western countries with similar social and demographic features. More studies about myopia progression risk factors among atropine treated patients are needed.

Stable Atropine Loaded Film As a Potential Ocular Delivery System For Treatment Of Myopia.

PURPOSE: The objective of the present study was to prepare stable and high bioavailability ocular atropine loaded films (ATR-films) as potential ocular drug delivery systems for the treatment of myopia. METHODS: ATR-films were prepared by the solvent casting method and the physical properties of films were evaluated including thickness, water content, light transparency, disintegration time, and mechanical properties. FT-IR, DSC, XRD, TGA, AFM, and Raman spectroscopy were performed to characterize the film. The stability test was conducted under different conditions, such as high humidity, high temperature, and strong light. The pharmacokinetic study and irritation assessment were conducted in rabbits. The efficacy of ATR-films was evaluated by refraction and ocular biometry in myopia guinea pigs. RESULT: After optimizing the formulation, the resulting ATR-film was flexible and transparent with lower water content (8.43% ± 1.25). As expected, the ATR-film was stable and hydrolysate was not detected, while the content of hydrolysate in ATR eye drops can reach up to 8.1867% (limit: < 0.2%) in the stability study. The safety assessment both in vitro and in vivo confirmed that the ATR-film was biocompatible. Moreover, the bioavailability (conjunctiva 3.21-fold, cornea 2.87-fold, retina 1.35-fold, sclera 2.05-fold) was greatly improved compared with the ATR eye drops in vivo pharmacokinetic study. The pharmacodynamic study results showed that the ATR-film can slow the progress of form-deprivation myopia (~ 100 ± 0.81D), indicating that it has a certain therapeutic effect on form-deprivation myopia. CONCLUSION: The ATR-film with good stability and high bioavailability will have great potential for the treatment of myopia.

Safety and efficacy of 0.02% and 0.01% atropine on controlling myopia progression: a 2-year clinical trial.

Four hundred myopic children randomly received atropine 0.02% (n = 138) or 0.01% (n = 142) in both eyes once-nightly or only wore single-vision spectacles (control group) (n = 120) for 2 years. Spherical equivalent refractive error (SER), axial length (AL), pupil diameter (PD), and amplitude of accommodation (AMP) were measured every 4 months. After 2 years, the SER changes were - 0.80 (0.52) D, - 0.93 (0.59) D and - 1.33 (0.72) D and the AL changes were 0.62 (0.29) mm, 0.72 (0.31) mm and 0.88 (0.35) mm in the 0.02% and 0.01% atropine groups and control group, respectively. There were significant differences between changes in SER and AL in the three groups (all P < 0.001). The changes in SER and AL in the 2nd year were similar to the changes in the 1st year in the three groups (all P > 0.05). From baseline to 2 years, the overall decrease in AMP and increase in PD were not significantly different in the two atropine groups, whereas the AMP and PD in the control group remained stable (all P > 0.05). 0.02% atropine had a better effect on myopia control than 0.01% atropine, and its effects on PD and AMP were similar to 0.01% atropine. 0.02% or 0.01% atropine controlled myopia progression and AL elongation synchronously and had similar effects on myopia control each year.

Evaluation of axial length to identify the effects of monocular 0.125% atropine treatment for pediatric anisometropia.

The aim of the study is to determine the effects of monocular 0.125% atropine daily treatment on the longer axial length (AL) eyes in children with pediatric anisometropia. This was a retrospective cohort study. The charts of children with anisometropia (aged 6-15 years) who had a > 0.2-mm difference in AL between the two eyes were reviewed. Children who received monocular treatment of 0.125% atropine in the eye with longer AL were included for final analysis. The main outcome measure was the difference in AL between the two eyes after treatment. Regression analysis was used to model the changes in AL according to the time of treatment in both eyes. Finally, forty eyes in 20 patients (mean age 10.2 years) were included in the analyses. During the treatment period, AL was controlled in the treated eyes (p = 0.389) but elongated significantly in the untreated eyes (p < 0.001). The difference in AL between the treated and untreated eyes decreased from 0.57 to 0.22 mm (p < 0.001) after the 1-year treatment period. In the regression model, the best fit for the relationship between changes in AL and time during the treatment period in the treated eyes was the quadratic regression model with a concave function. In conclusion, these data suggest that 0.125% atropine daily is an effective treatment to reduce the interocular difference of AL in eyes with axial anisometropia. This pilot study provides useful information for future prospective and larger studies of atropine for the treatment of pediatric axial anisometropia.

Parasympathetic, but not sympathetic denervation, suppressed colorectal cancer progression.

Disruption in the nerve-tumor interaction is now considered as a possible anticancer strategy for treating various cancer types, particularly colorectal cancer. However, the underlying mechanisms are not still fully understood. Therefore, the present study aimed to evaluate the effects of sympathetic and parasympathetic denervation on the inhibition of colorectal cancer progression in early and late phases and assess the involvement of nerve growth factor in denervation mediated anticancer effects. One-hundred and fifty male Wistar rats were assigned into 15 groups. Seven groups comprising the control group, 1,2-dimethylhydrazine (DMH) group, sympathetic denervation group (celiac-mesenteric ganglionectomy and guanethidine sulphate administration), parasympathetic denervation group (vagotomy and atropine administration), and combination group were used in the early-stage protocol. For the late-stage protocol, eight groups comprising the control, DMH, surgical and pharmacological sympathetic and parasympathetic denervation groups, combination group, and 5-flourouracil group were considered. After 8 weeks, sympathetic and parasympathetic denervation significantly reduced ACF numbers in rats receiving DMH. On the other hand, in the late stages, parasympathetic but not sympathetic denervation resulted in significant reductions in tumor incidence, tumor volume and weight, cell proliferation (indicated by reduced immunostaining of PCNA and ki-67), and angiogenesis (indicated by reduced immunostaining of CD31 and VEGF expression levels), and downregulated NGF, ß2 adrenergic, and M3 receptors. It can be concluded that parasympathetic denervation may be of high importance in colon carcinogenesis and suggested as a possible therapeutic modality in late stages of colorectal cancer.

Influence of coronavirus disease 2019 on myopic progression in children treated with low-concentration atropine.

PURPOSE: The outbreak of coronavirus disease 2019 (COVID-19) has caused many children to stay indoors. Increased near work and insufficient outdoor activities are considered important risk factors for myopic progression. This study aimed to compare the changes in myopic progression before and after COVID-19 in children treated with low-concentration atropine. METHODS: The records of 103 eyes of 103 children who were treated with low-concentration atropine eye drops were retrospectively reviewed. We classified children according to the concentration of atropine eye drops and children's age. The beginning of the pre-COVID-19 period was set from January 2019 to May 2019, and the endpoint was set in March 2020. The beginning of the post-COVID-19 period was set in March 2020, and the endpoint was set from January 2021 to March 2021. We evaluated the questionnaires administered to children's parents. RESULTS: A significant myopic progression was observed in the post-COVID-19 period compared to the pre-COVID-19 period in the 0.05% and 0.025% atropine groups (P < 0.001 and P = 0.020, respectively). For children aged 5 to 7 and 8 to 10 years, the axial elongations were significantly faster in the post-COVID-19 period than in the pre-COVID-19 period (P = 0.022 and P = 0.005, respectively). However, the rates of axial elongation and myopic progression were not significantly different between pre- and post-COVID-19 in children aged 11 to 15 years (P = 0.065 and P = 0.792, respectively). The average time spent using computers and smartphones and reading time were significantly increased, and the times of physical and outdoor activity were significantly decreased in the post-COVID-19 period compared to the pre-COVID-19 period. CONCLUSIONS: The rates of myopic progression have increased substantially after the spread of COVID-19 with an increase in the home confinement of children. Therefore, it is necessary to control the environmental risk factors for myopia, even in children undergoing treatment for the inhibition of myopic progression.