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JAMA Feb 2023Early onset of myopia is associated with high myopia later in life, and myopia is irreversible once developed. (Randomized Controlled Trial)
Randomized Controlled 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.
Topics: Child; Female; Humans; Male; Atropine; Disease Progression; Incidence; Mydriatics; Myopia; Ophthalmic Solutions; Refraction, Ocular; Age of Onset; Double-Blind Method; Child, Preschool
PubMed: 36786791
DOI: 10.1001/jama.2022.24162 -
Emergency Medicine Clinics of North... Feb 2022Anaphylaxis is a potentially life-threatening, multisystem allergic reaction that can cause airway, breathing, or circulatory compromise. Intramuscular epinephrine is... (Review)
Review
Anaphylaxis is a potentially life-threatening, multisystem allergic reaction that can cause airway, breathing, or circulatory compromise. Intramuscular epinephrine is the immediate treatment of all patients. Intravenous epinephrine should be used in patients in shock, either as a bolus or infusion, along with fluid resuscitation. Airway obstruction must be recognized, and early intubation may be necessary. For shock that is refractory to epinephrine, additional vasopressors may be needed. Disposition depends on patient presentation and response to treatment. Mandatory observation periods are not necessary, because biphasic reactions are difficult to predict and may occur outside of typical observation periods.
Topics: Airway Management; Anaphylaxis; Emergency Medicine; Epinephrine; Fluid Therapy; Humans; Risk Factors; Vasoconstrictor Agents
PubMed: 34782088
DOI: 10.1016/j.emc.2021.08.004 -
Ophthalmology Mar 2022Comparative efficacy and safety of different concentrations of atropine for myopia control. (Comparative Study)
Comparative Study Meta-Analysis Review
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.
Topics: Administration, Ophthalmic; Adolescent; Atropine; Axial Length, Eye; Child; Female; Humans; Male; Mydriatics; Myopia; Network Meta-Analysis; Ophthalmic Solutions; Treatment Outcome; Visual Acuity
PubMed: 34688698
DOI: 10.1016/j.ophtha.2021.10.016 -
European Journal of Ophthalmology May 2023This article is about the accommodation spasm. The primary rule for near vision is ciliary muscle constriction, synchronised convergence of both eyes, and pupil... (Review)
Review
This article is about the accommodation spasm. The primary rule for near vision is ciliary muscle constriction, synchronised convergence of both eyes, and pupil constriction. Any weaknesses in these components could result in an accommodative spasm. Variable retinoscopic reflex, unstable refractive error, and lead of accommodation in near retinoscopy are common causes of spasm. We conducted a thorough literature search in the PubMed and Google Scholar databases for published journals prior to June 2022, with no data limitations. This review contains twenty-eight case reports, six cohort studies, four book references, four review articles, and two comparative studies after applying the inclusion and exclusion criteria. The majority of studies looked at accommodative spasm, near reflex spasm, and pseudomyopia. The most common causes of accommodative spasm are excessive close work, emotional distress, head injury, and strabismus. Despite side effects or an insufficient regimen, cycloplegic drops are effective in diagnosing accommodation spasm. The modified optical fogging technique is also effective and may be an option for treating accommodative spasm symptoms. Bifocals for near work, manifest refraction, base-in prisms, and vision therapy are some of the other management options. As a result, it requires a comprehensive clinical treatment strategy. This review aims to investigate the various aetiology and treatments responsible for accommodative spasm and proposes widely implementing the modified optical fogging method and vision therapy in clinics as comprehensive management to reduce the future upward trend of accommodative spasm.
Topics: Humans; Refractive Errors; Accommodation, Ocular; Spasm; Myopia; Mydriatics; Vision, Low
PubMed: 36384286
DOI: 10.1177/11206721221136438 -
Asia-Pacific Journal of Ophthalmology... 2019Atropine eye drops is an emerging therapy for myopia control. This article reviews the recent clinical trials to provide a better understanding of the use of atropine... (Review)
Review
PURPOSE
Atropine eye drops is an emerging therapy for myopia control. This article reviews the recent clinical trials to provide a better understanding of the use of atropine eye drops on myopia progression.
METHODS
All randomized clinical trials of atropine eye drops for myopia progression in the literatures were reviewed.
RESULTS
Atropine eye drops 1% conferred the strongest efficacy on myopia control. However, its use was limited by the side effects of blurred near vision and photophobia. ATOM 2 study evaluated 0.5%, 0.1%, and 0.01% atropine on 400 myopic children, and suggested that 0.01% is the optimal concentration with good efficacy and minimal side effects. Since then, the use of atropine eye drops has been transitioned from high-concentration to low-concentration worldwide. Recent Low-concentration Atropine for Myopia Progression (LAMP) study evaluated 0.05%, 0.025%, 0.01% atropine eye drops and placebo group in 438 myopic children. The study firstly provided placebo-compared evidence of low-concentration atropine eye drops in myopia control. Furthermore, both efficacy and side effects followed a concentration-dependent response within 0.01% to 0.05% atropine. Among them, 0.05% atropine was the optimal concentration to achieve best efficacy and safety profile.
CONCLUSIONS
Low concentration atropine is effective in myopia control. The widespread use of low-concentration atropine, especially in East Asia, may help prevent the myopia progression for the high-risk children. Further investigations on the rebound phenomenon following drops cessation, and longer-term individualized treatment approach should be warranted.
Topics: Atropine; Disease Progression; Dose-Response Relationship, Drug; Humans; Mydriatics; Myopia, Degenerative; Ophthalmic Solutions; Refraction, Ocular
PubMed: 31478936
DOI: 10.1097/APO.0000000000000256 -
Ophthalmology Nov 2022To evaluate the efficacy of time outdoors per school day over 2 years on myopia onset and shift. (Randomized Controlled Trial)
Randomized Controlled Trial
PURPOSE
To evaluate the efficacy of time outdoors per school day over 2 years on myopia onset and shift.
DESIGN
A prospective, cluster-randomized, examiner-masked, 3-arm trial.
PARTICIPANTS
A total of 6295 students aged 6 to 9 years from 24 primary schools in Shanghai, China, stratified and randomized by school in a 1:1:1 ratio to control (n = 2037), test I (n = 2329), or test II (n = 1929) group.
METHODS
An additional 40 or 80 minutes of outdoor time was allocated to each school day for test I and II groups. Children in the control group continued their habitual outdoor time. Objective monitoring of outdoor and indoor time and light intensity each day was measured with a wrist-worn wearable during the second-year follow-up.
MAIN OUTCOME MEASURES
The 2-year cumulative incidence of myopia (defined as cycloplegic spherical equivalent [SE] of ≤-0.5 diopters [D] in the right eye) among the students without myopia at baseline and changes in SE and axial length (AL) after 2 years.
RESULTS
The unadjusted 2-year cumulative incidence of myopia was 24.9%, 20.6%, and 23.8% for control, test I, and II groups, respectively. The adjusted incidence decreased by 16% (incidence risk ratio [IRR], 0.84; 95% confidence interval [CI], 0.72-0.99; P = 0.035) in test I and 11% (IRR = 0.89; 95% CI, 0.79-0.99; P = 0.041) in test II when compared with the control group. The test groups showed less myopic shift and axial elongation compared with the control group (test I: -0.84 D and 0.55 mm, test II: -0.91 D and 0.57 mm, control: -1.04 D and 0.65 mm). There was no significant difference in the adjusted incidence of myopia and myopic shift between the 2 test groups. The test groups had similar outdoor time and light intensity (test I: 127 ± 30 minutes/day and 3557 ± 970 lux/minute; test II: 127 ± 26 minutes/day and 3662 ± 803 lux/minute) but significantly more outdoor time and higher light intensity compared with the control group (106 ± 27 minutes/day and 2984 ± 806 lux/minute). Daily outdoor time of 120 to 150 minutes at 5000 lux/minutes or cumulative outdoor light intensity of 600 000 to 750 000 lux significantly reduced the IRR by 15%~ 24%.
CONCLUSIONS
Increasing outdoor time reduced the risk of myopia onset and myopic shifts, especially in nonmyopic children. The protective effect of outdoor time was related to the duration of exposure and light intensity. The dose-response effect between test I and test II was not observed probably because of insufficient outdoor time achieved in the test groups, which suggests that proper monitoring on the compliance on outdoor intervention is critical if one wants to see the protective effect.
Topics: Child; Humans; Prospective Studies; Mydriatics; China; Myopia; Refraction, Ocular; Schools
PubMed: 35779695
DOI: 10.1016/j.ophtha.2022.06.024 -
Eye & Contact Lens May 2020Myopia 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... (Review)
Review
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.
Topics: Atropine; Child; Disease Progression; Humans; Muscarinic Antagonists; Mydriatics; Myopia; Ophthalmic Solutions; Refraction, Ocular
PubMed: 31899695
DOI: 10.1097/ICL.0000000000000677 -
Ophthalmology Feb 2023Repeated low-level red-light (RLRL) therapy is an emerging treatment for myopia control. Nevertheless, previous studies are limited by open-label design. Our study aimed... (Randomized Controlled Trial)
Randomized Controlled Trial
PURPOSE
Repeated low-level red-light (RLRL) therapy is an emerging treatment for myopia control. Nevertheless, previous studies are limited by open-label design. Our study aimed to assess the efficacy and safety of RLRL therapy in controlling myopia progression compared to a sham device with only 10% of the original power.
DESIGN
Randomized, double-blind, controlled clinical trial.
PARTICIPANTS
A total of 112 Chinese children aged 7 to 12 years with myopia of at least -0.50 diopter (D), astigmatism of 1.50 D or less, and anisometropia of 1.50 D or less.
METHODS
Participants were assigned randomly in a 1:1 ratio to the RLRL group or the sham device control group, following a schedule of 3 minutes per session, twice daily, with an interval between sessions of at least 4 hours. The RLRL therapy was provided by a desktop red-light therapy device and administered at home. The sham device was the same device but with only 10% of the original device's power. Cycloplegic refraction and axial length (AL) were measured at baseline and 6 months.
MAIN OUTCOME MEASURES
Changes in cycloplegic spherical equivalence refraction (SER) and AL between 2 groups were compared using a generalized estimating equation (GEE).
RESULTS
A total of 111 children were included in the analysis (n = 56 in the RLRL group and n = 55 in the sham device control group). The mean SER change over 6 months was 0.06 ± 0.30 D in the RLRL group and -0.11 ± 0.33 D in the sham device control group (P = 0.003), with respective mean increases in AL of 0.02 ± 0.11 mm and 0.13 ± 0.10 mm (P < 0.001). In the multivariate GEE models, children in the RLRL group showed less myopia progression and axial elongation than those in the sham device control group (SER: coefficient, 0.167 D; 95% confidence interval [CI], 0.050-0.283 D; P = 0.005; AL: coefficient, -0.101 mm; 95% CI, -0.139 to -0.062 mm; P < 0.001). No treatment-related adverse events were reported.
CONCLUSIONS
In myopic children, RLRL therapy with 100% power significantly reduced myopia progression over 6 months compared with those treated with a sham device of 10% original power. The RLRL treatment was well tolerated without treatment-related adverse effects.
Topics: Humans; Child; Mydriatics; East Asian People; Myopia; Refraction, Ocular; Phototherapy; Disease Progression
PubMed: 36049646
DOI: 10.1016/j.ophtha.2022.08.024 -
Ophthalmology Mar 2022(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... (Comparative Study)
Comparative Study Randomized Controlled Trial
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.
Topics: Atropine; Axial Length, Eye; Child; Child, Preschool; Double-Blind Method; Female; Follow-Up Studies; Humans; Male; Mydriatics; Myopia, Degenerative; Refraction, Ocular; Sickness Impact Profile; Treatment Outcome; Visual Acuity
PubMed: 34627809
DOI: 10.1016/j.ophtha.2021.10.002 -
Drugs Feb 2022Corneal injuries can occur secondary to traumatic, chemical, inflammatory, metabolic, autoimmune, and iatrogenic causes. Ocular infection may frequently occur concurrent... (Review)
Review
Corneal injuries can occur secondary to traumatic, chemical, inflammatory, metabolic, autoimmune, and iatrogenic causes. Ocular infection may frequently occur concurrent to corneal injury; however, antimicrobial agents are excluded from this present review. While practitioners may primarily rely on clinical examination techniques to assess these injuries, several pharmacological agents, such as fluorescein, lissamine green, and rose bengal, can be used to formulate a diagnosis and develop effective treatment strategies. Practitioners may choose from several analgesic medications to help with patient comfort without risking further injury or delaying ocular healing. Atropine, cyclopentolate, scopolamine, and homatropine are among the most frequently used medications for this purpose. Additional topical analgesic agents may be used judiciously to augment patient comfort to facilitate diagnosis. Steroidal anti-inflammatory agents are frequently used as part of the therapeutic regimen. A variety of commonly used agents, including prednisolone acetate, loteprednol, difluprednate, dexamethasone, fluorometholone, and methylprednisolone are discussed. While these medications are effective for controlling ocular inflammation, side effects, such as elevated intraocular pressure and cataract formation, must be monitored by clinicians. Non-steroidal medications, such as ketorolac, bromfenac, nepafenac, and diclofenac, are additionally used for their efficacy in controlling ocular inflammation without incurring side effects seen with steroids. However, these agents have their own respective side effects, warranting close monitoring by clinicians. Additionally, ophthalmologists routinely employ several agents in an off-label manner for supplementary control of inflammation and treatment of corneal injuries. Patients with corneal injuries not infrequently have significant ocular surface disease, either as a concurrent pathology or as an exacerbation of previously existing disease. Several agents used in the management of ocular surface disease have also been found to be useful as part of the therapeutic armamentarium for treatment of corneal injuries. For example, several antibiotics, such as doxycycline and macrolides, have been used for their anti-inflammatory effects on specific cytokines that are upregulated during acute injuries. There has been a recent wave of interest in amniotic membrane therapies (AMTs), including topical, cryopreserved and dehydrated variants. AMT is particularly effective in ocular injuries with violation of corneal surface integrity due to its ability to promote re-epithelialization of the corneal epithelium. Blood-based therapies, including autologous serum tears, plasma-enriched growth factor eyedrops and autologous blood drops, have additionally been explored in small case series for effectiveness in challenging and recalcitrant cases. Protection of the ocular surface is also a vital component in the treatment of corneal injuries. Temporary protective methods, such as bandage contact lenses and mechanical closure of the eyelids (tarsorrhaphy) can be particularly helpful in selective cases. Glue therapies, including biologic and non-biologic variants, can also be used in cases of severe injury and risk of corneal perforation. Finally, there are a variety of recently introduced and in-development agents that may be used as adjuvant therapies in challenging patient populations. Neurotrophic corneal disease may occur as a result of severe or chronic injury. In such cases, recombinant human nerve growth factor (cenegermin), topical insulin, and several other novel agents may be an alternate and effective option for clinicians to consider.
Topics: Adhesives; Adrenal Cortex Hormones; Amnion; Anti-Bacterial Agents; Anti-Inflammatory Agents, Non-Steroidal; Cornea; Corneal Injuries; Fluorescent Dyes; Humans; Mydriatics; Patient Acuity
PubMed: 35025078
DOI: 10.1007/s40265-021-01660-5