Repeated Low-Level Red-Light Therapy for Controlling Onset and Progression of Myopia-a Review.

Repeated low-level red-light (RLRL), characterized by increased energy supply and cellular metabolism, thus enhancing metabolic repair processes, has gained persistent worldwide attention in recent years as a new novel scientific approach for therapeutic application in myopia. This therapeutic revolution led by RLRL therapy is due to significant advances in bioenergetics and photobiology, for instance, enormous progresses in photobiomodulation regulated by cytochrome c oxidase, the primary photoreceptor of the light in the red to near infrared regions of the electromagnetic spectrum, as the primary mechanism of action in RLRL therapy. This oxidase is also a key mitochondrial enzyme for cellular bioenergetics, especially for the nerve cells in the retina and brain. In addition, dopamine (DA)-enhanced release of nitric oxide may also be involved in controlling myopia by activation of nitric oxide synthase, enhancing cGMP signaling. Recent evidence has also suggested that RLRL may inhibit myopia progression by inhibiting spherical equivalent refraction (SER) progression and axial elongation without adverse effects. In this review, we provide scientific evidence for RLRL therapy as a unique paradigm to control myopia and support the theory that targeting neuronal energy metabolism may constitute a major target for the neurotherapeutics of myopia, with emphasis on its molecular, cellular, and nervous tissue levels, and the potential benefits of RLRL therapy for myopia.

Mechanism of Chinese botanical drug Dizhi pill for myopia: An integrated study based on bioinformatics and network analysis.

To identify the active constituents, core targets, immunomodulatory functions and potential mechanisms of Dizhi pill (DZP) in the treatment of myopia. The active constituents and drug targets of DZP were searched in the TCMSP, Herb databases and correlational studies. The targets of myopia were searched in the TTD, Genecards, OMIM and Drugbank databases. Gene expression profile data of GSE136701 were downloaded from the GEO database and subjected to WGCNA and DEG analysis to screen for significant modules and targets of myopia. Intersectional targets of myopia and DZP and core targets of myopia were analyzed through the String database. The GO and KEGG enrichment analyses of the interested targets were conducted. Cibersort algorithm was used for immune infiltration analysis to investigate the immunomodulatory functions of DZP on myopia. Autodock was used to dock the important targets and active constituents. Eight targets (STAT3, PIK3CA, PIK3R1, MAPK1, MAPK3, HSP90AA1, MIP, and LGSN) and 5 active constituents (Quercetin, Beta-sitosterol, Diincarvilone A, Ferulic acid methyl ester, and Naringenin) were identified from DZP. In pathways identified by the GO and KEGG enrichment analyses, "ATP metabolic process" and "AGE-RAGE diabetes complication signaling" pathways were closely related to the mechanisms of DZP in the treatment of myopia. Molecular docking showed that both the intersectional targets and core targets of myopia could bind stably and spontaneously with the active constituents of DZP. This study suggested that the mechanisms of DZP in the treatment of myopia were related to active constituents: Quercetin, Beta-sitosterol, Diincarvilone A, Ferulic acid methyl ester and Naringenin, intersectional targets: STAT3, PIK3CA, PIK3R1, MAPK1, MAPK3, and HSP90AA1, core targets of myopia: MIP and LGSN, AGE-RAGE signaling pathway, positive regulation of ATP metabolic process pathway and immunomodulatory functions.

Inhibitory Effect of Jinkui Shenqi Pills on Glucocorticoid-Enhanced Axial Length Elongation in Experimentally Myopic Guinea Pigs.

OBJECTIVE: To explore the underlying mechanism of inhibition by Jinkui Shenqi Pills (JKSQP) on glucocorticoid-enhanced axial length elongation in experimental lens-induced myopia (LIM) guinea pigs. METHODS: Sixty 2-week old male guinea pigs were randomly divided into 4 groups with 15 guinea pigs in each group, according to the random numbers generated by SPSS software: control, LIM, saline and JKSQP groups. The control group includes animals with no treatment, while the guinea pigs in the other 3 groups received lens-induced myopization on the right eyes throughout the experiment (for 8 weeks). The saline and JKSQP groups were given daily intraperitoneal injections of 10 mg/kg hydrocortisone for 2 consecutive weeks at the same time, and then orally administered either saline or JKSQP [13.5 g/(kg•d) for 6 consecutive weeks. Body weight, anal temperature and animal appearance were observed and recorded to evaluate the GC-associated symptoms. The ocular parameters, including refraction and axial length, were measured by streak retinoscopy and A-scan ultrasonography, respectively. The levels of plasma hormones associated with the hypothalamic-pituitary-adrenal axis (HPAA), including free triiodothyronine, free thyroxine, estradiol and testosterone, were measured by radioimmunoassay, and cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate were measured by enzyme-linked immunosorbent assay. In addition, the mRNA and protein expressions of retinal amphiregulin (AREG) was measured by quantitative real-time polymerase chain reaction and Western blotting, respectively. RESULTS: JKSQP effectively increased body weight and anal temperature, improved animal appearance and suppressed axial length elongation in glucocorticoid-enhanced myopic guinea pigs with normalization of 4 HPAA-associated plasma hormones (all P<0.05). The plasma level of cAMP was significantly increased, whereas the plasma level of cGMP and the mRNA and protein expressions of retinal AREG were decreased after treatment with JKSQP (all P<0.05). CONCLUSION: JKSQP exhibited a significant inhibitory effect on axial length elongation with decreased expression of AREG in the retina, and normalized 4 HPAA-associated plasma hormones and the expression of cAMP and cGMP in GC-enhanced myopic guinea pigs.

Addition of Auricular Acupoint Stimulation to 0.01% Atropine for Myopia: 12-Month Results from a Randomized Trial.

Introduction: A previous 6-month report showed that adjunctive auricular acupoint stimulation (AAS) slowed myopia progression compared with 0.01% atropine (0.01% A) alone. This 12-month report was to determine whether the antimyopic effect of AAS, when added to 0.01% A, continued beyond treatment cessation, and explore the mode of action of AAS from the accommodative response. Design and Interventions: One hundred four children were randomly assigned to either a 0.01% A group or a 0.01% A + AAS group. Participants in the 0.01% A + AAS group received AAS in addition to 0.01% A for 6 months, and then kept using 0.01% A for the following 6 months. Participants in the 0.01% A group only used 0.01% A. The primary outcome was the difference in the mean cycloplegic spherical equivalent refraction (SER) from the baseline to the 12-month visit. Secondary outcomes included axial length (AL) and accommodative lag assessments. Results: The adjusted mean change from baseline to month 12 in the SER was -0.62 D for 0.01% A and -0.46 D for 0.01% A + AAS (difference, 0.16 D; p = 0.01), with a respective mean increase of 0.37 and 0.31 mm in AL (difference, -0.05 mm; p = 0.05). For the 5D near target, there was a reduction in the accommodative lag in children receiving add-on AAS relative to 0.01% A alone at 1 and 6 months (both p = 0.002). Conclusions: AAS treatment produced additional benefits >0.01% A in slowing myopia progression over the 12-month period, where the efficacy was sustained after the cessation of AAS. An effect of add-on AAS on reducing accommodative lag in response to 5D stimulus was found, but its role in mediating therapeutic response remained unclear. Chinese Clinical Trial Registry number: ChiCTR1900021316.

Efficacy of lutein supplements on macular pigment optical density in highly myopic individuals: A randomized controlled trial.

INTRODUCTION: Lutein supplementation is beneficial in preventing maculae from developing serious ocular diseases. This study aimed to evaluate the efficacy and safety of lutein administration in patients with high myopia (HM). METHODS: In a single-center randomized double-blinded placebo-controlled trial conducted over 24 months, 22 eyes were enrolled in lutein and control groups. Among them, 15 eyes in the lutein group and 13 eyes in the control group completed the study. All patients with HM (axial length > 26.00) were administered lutein (20 mg) or placebo once daily for 6 months. The macular pigment optical density (MPOD), rate of change in MPOD, visual acuity, contrast sensitivity, and electroretinogram after administration were examined at baseline, 3 months, and 6 months. RESULTS: The baseline MPOD in the control and lutein groups was 0.71 ± 0.21 and 0.70 ± 0.22, respectively. The MPOD in the control and lutein groups at 3 months was 0.70 ± 0.21 and 0.70 ± 0.25, respectively, and at 6 months was 0.66 ± 0.20 and 0.72 ± 0.27, respectively, which was not significantly different from those at baseline or between the groups. The MPOD significantly increased from baseline in the lutein group with less than 28.25 mm of axial length at 6 months (from 0.71 ± 0.20 to 0.78 ± 0.22, P = .02, t test). visual acuity, contrast sensitivity, and electroretinogram values were similar between the groups. CONCLUSION: Lutein supplementation showed significant benefits in MPOD augmentation in patients with HM.

Myopia Control Effect of Repeated Low-Level Red-Light Therapy in Chinese Children: A Randomized, Double-Blind, Controlled Clinical 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.

Efficacy Comparison of Repeated Low-Level Red Light and Low-Dose Atropine for Myopia Control: A Randomized Controlled Trial.

Purpose: To compare the treatment efficacy between repeated low-level red light (RLRL) therapy and 0.01% atropine eye drops for myopia control. Methods: A single-masked, single-center, randomized controlled trial was conducted on children 7 to 15 years old with cycloplegic spherical equivalent refraction (SER) ≤ -1.00 diopter (D) and astigmatism ≤ 2.50 D. Participants were randomly assigned to the RLRL group or low-dose atropine (LDA, 0.01% atropine eye drops) group and were followed up at 1, 3, 6, and 12 months. RLRL treatment was provided by a desktop light therapy device that emits 650-nm red light. The primary outcome was the change in axial length (AL), and the secondary outcome was the change in SER. Results: Among 62 eligible children equally randomized to each group (31 in the RLRL group, 31 in the LDA group), 60 children were qualified for analysis. The mean 1-year change in AL was 0.08 mm (95% confidence interval [CI], 0.03-0.14) in the RLRL group and 0.33 mm (95% CI, 0.27-0.38) in the LDA group, with a mean difference (MD) of -0.24 mm (95% CI, -0.32 to -0.17; P < 0.001). The 1-year change in SER was -0.03 D (95% CI, -0.01 to -0.08) in the RLRL group and -0.60 D (95% CI, -0.7 to -0.48) in the LDA group (MD = 0.57 D; 95% CI, 0.40-0.73; P < 0.001). The progression of AL < 0.1 mm was 53.2% and 9.7% (P < 0.001) in the RLRL and LDA groups, respectively. For AL ≥ 0.36 mm, progression was 9.7% and 50.0% (P < 0.001) in the RLRL and LDA groups, respectively. Conclusions: In this study, RLRL was more effective for controlling AL and myopia progression over 12 months of use compared with 0.01% atropine eye drops. Translational Relevance: RLRL therapy significantly slows axial elongation and myopia progression compared with 0.01% atropine; thus, it is an effective alternative treatment for myopia control in children.

Efficacy and safety of traditional Chinese medicine decoction in the treatment of adolescent myopia: A protocol for systematic review and network meta-analysis.

BACKGROUND: Adolescent myopia has become a major public health problem in Asian countries and even the world. Due to its unstable prognosis and numerous complications, it has caused serious social and economic burden. As a common treatment in Asia, Chinese medicine has been shown to be effective in controlling the development of myopia, but its evidence-based medical evidence is not sufficient. Therefore, the purpose of this study is to evaluate the efficacy and safety of traditional Chinese medicine (TCM) in the treatment of adolescent myopia through network meta-analysis, and to provide evidence for clinical and scientific research. METHODS: We searched seven databases for randomized controlled trials of TCM decoction for adolescent myopia, including PubMed, the Cochrane Library, EMbase, China National Knowledge Infrastructure, China Biological Medicine, Chinese Scientific Journals Database, and wan-fang databases, from the date of the establishment of each database to January 31, 2022. The network meta-analysis will be implemented through Aggregate Data Drug Information System 1.16.8 and Stata 13.0 software. Primary outcomes include distant vision, intraocular pressure, and diopter. Mean differences or odds ratios will be used for statistical analysis. We will ensure the reliability of the results through node-split model and heterogeneity analysis. In addition, the Cochrane Collaboration's tool and Grading of Recommendations Assessment, Development and Evaluation system will be used for the methodological quality and the evidence quality. RESULTS: This study will provide reliable evidence for the clinical selection of TCM decoction in the treatment of adolescent myopia. CONCLUSION: The results of this study will evaluate the efficacy and safety of TCM decoction in the treatment of adolescent myopia, and provide decision-making references for future clinical and scientific research. ETHICS AND DISSEMINATION: This study did not require ethical approval. We will disseminate our findings by publishing results in a peer-reviewed journal. OSF REGISTRATION NUMBER: DOI 10.17605/OSF.IO/VXQUP.

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.

Stepwise candidate drug screening for myopia control by using zebrafish, mouse, and Golden Syrian Hamster myopia models.

BACKGROUND: We developed a preclinical protocol for the screening of candidate drugs able to control myopia and prevent its progression. The protocol uses zebrafish, C57BL/6 mice, and golden Syrian hamster models of myopia. METHODS: A morpholino (MO) targeting the zebrafish lumican gene (zlum) was injected into single-cell zebrafish embryos, causing excessive expansion of the sclera. A library of 640 compounds with 2 matrix metalloproteinase (MMP) inhibitors (marimastat and batimastat), which have the potential to modulate scleral remodelling, was screened to identify candidates for mitigating scleral diameter expansion in zlum-MO-injected embryos. The myopia-prevention ability of compounds discovered to have superior potency to inhibit scleral expansion was validated over 4 weeks in 4-week-old C57BL/6 mice and 3-week-old golden Syrian hamsters with form-deprivation myopia (FDM). Changes in the refractive error and axial length were investigated. Scleral thickness, morphology of collagen fibrils in the posterior sclera, messenger RNA (mRNA) expressions, and protein levels of transforming growth factor-ß2 (TGF-ß2), tissue inhibitor of metalloproteinase-2 (TIMP-2), MMP-2, MMP-7, MMP-9, and collagen, type I, alpha 1 (collagen Iα1) were investigated in C57BL/6 mice, and MMP-2, MMP-9, and MMP activity assays were conducted in these mice. FINDINGS: In the zebrafish experiment, atropine, marimastat, batimastat, doxycycline, and minocycline were the drugs that most effectively reduced expansion of scleral equatorial diameter. After 28-day treatment in diffuser-wearing mice and 21-day treatment in lid-sutured hamsters, myopic shift and axial elongation were significantly mitigated by eye drops containing 1% atropine, 50 µM marimastat, 5 µM batimastat, or 200 µM doxycycline. MMP-2 mRNA expression in mouse sclera was lower after treatment with atropine, marimastat, batimastat, or doxycycline. The protein levels and activity of MMP-2 and MMP-7 were significantly reduced after treatment with atropine, marimastat, batimastat, doxycycline, and minocycline. Furthermore, scleral thickness and collagen fibril diameter were not lower after treatment with atropine, marimastat, batimastat, or doxycycline than those of occluded eyes. INTERPRETATION: Stepwise drug screening in a range of models from zlum-MO-injected zebrafish to rodent FDM models identified effective compounds for preclinical myopia control or prevention. On the basis of the 640 compounds that were screened, MMP inhibitors may offer alternatives for clinical trials. FUNDING: This research was supported by grants from Taiwan's Ministry of Science and Technology and Ministry of Health and Welfare.

Efficacy and safety of Bu Jing Yi Shi tables for high myopia: A protocol of systematic review and meta-analysis.

BACKGROUND: High myopia is a kind of ametropia with diopter more than -6.00D or axial length ≥26 mm. With the change of the modern environment, the incidence rate is increasing year by year. At present, the pathogenesis of high myopia is not clear. Some current studies indicate that it may be related to the environment and genetics. A Chinese patent medicine named Bu Jing Yi Shi Tablets (BJYST) has many functions including anti-oxidation, expansion of blood vessels, anti-inflammatory, immune regulation, inhibition of retinal photoreceptor cell apoptosis, and promotion of retinal repair. A large number of existing studies have shown that this prescription can relieve the clinical manifestations of high myopia and its complications, but its true efficacy and safety are still unclear. To certify this point, a protocol for a systematic review and meta-analysis of BJYST for high myopia will be performed. METHODS AND ANALYSIS: Articles that have been identified by electronically searching of 9 English and 5 Chinese databases from their inception to December 4, 2020 will be incorporated into the study. This study only adopts Chinese and English. Two researchers will take charge of completing the selection of research, the extraction of data as well as the assessment of research quality independently. The primary outcomes will be an average change in refractive error measured in diopters and an average change in axial length measured in millimeters. Data analysis will be performed via the RevMan 5.3 software, and Grading of Recommendations Assessment, Development, and Evaluation (GRADE) will help to assess the evidence level. RESULTS: The results of this study will be published in a peer-reviewed journal. CONCLUSION: This study will conclude whether BJYST is safe and effective in treating high myopia on the basis of evidence-based medicine. REGISTRATION: The Open Science Framework (OSF) registration number is osf.io/dpk5b.

Lutein Supplementation for Eye Diseases.

Lutein is one of the few xanthophyll carotenoids that is found in high concentration in the macula of human retina. As de novo synthesis of lutein within the human body is impossible, lutein can only be obtained from diet. It is a natural substance abundant in egg yolk and dark green leafy vegetables. Many basic and clinical studies have reported lutein's anti-oxidative and anti-inflammatory properties in the eye, suggesting its beneficial effects on protection and alleviation of ocular diseases such as age-related macular degeneration, diabetic retinopathy, retinopathy of prematurity, myopia, and cataract. Most importantly, lutein is categorized as Generally Regarded as Safe (GRAS), posing minimal side-effects upon long term consumption. In this review, we will discuss the chemical structure and properties of lutein as well as its application and safety as a nutritional supplement. Finally, the effects of lutein consumption on the aforementioned eye diseases will be reviewed.

Effect of plum-blossom needling versus tropicamide eye drops on adolescent myopia: protocol for a randomized crossover trial.

OBJECTIVE: Myopia is the most common eye problem and affects an estimated 28.3% of the global population. Its incidence is increasing annually. Myopia treatment is limited to correcting visual acuity. Acupuncture is one of the main therapies in traditional Chinese medicine and includes plum-blossom needling, which has been widely used for both the prevention and treatment of adolescent myopia. We hypothesized that plum-blossom needling would be effective in treating myopia compared with a tropicamide eye drops control. METHODS: This is a crossover randomized controlled trial involving adolescents with myopia. Participants will be randomized 1∶1 to plum-blossom needle or tropicamide eye drops arms. Subjects in each arm will be treated for 20 d, followed by a 1-month washout period and treatment change for another 20 d. The primary outcome is uncorrected distance and cycloplegic refractive errors. The secondary outcomes comprise corneal curvature, lens thickness, axial length, ciliary body thickness, accommodation amplitude, the NRA/PRA (negative/positive relative accommodation), flexible adjustment, and near point of convergence. The outcome measures will be assessed at baseline, after the first treatment course (the first month), at the end of the washout period (the second month), after the second treatment course (the third month), and at follow-up (the sixth month). DISCUSSION: The results of the trial will help to provide evidence for the efficacy of plum-blossom needling for myopia in China.

Photorefractive intrastromal corneal crosslinking for treatment of low myopia: clinical outcomes using the transepithelial approach with supplemental oxygen.

PURPOSE: To evaluate the safety and efficacy of photorefractive intrastromal corneal crosslinking (PiXL) for the treatment of low myopia using the epithelium-on approach with supplemental oxygen. SETTING: The Eye Foundation, Coimbatore, India. DESIGN: Prospective interventional case series. METHODS: Myopic nonectatic eyes underwent PiXL using the Mosaic system. Ultraviolet-A (UV-A) irradiation of 365 nm wavelength was delivered in an accelerated (30 mW/cm) pulsed approach to provide a total fluence of 15 J/cm. Supplemental oxygen (concentration greater than 95%) was provided to increase the efficacy of the epithelium-on approach during the UV-A irradiation. Efficacy was determined by improvement in mean refractive spherical equivalent (MRSE), uncorrected distance visual acuity (UDVA), and keratometric flattening. Safety was determined by loss of lines of corrected distance visual acuity, endothelial cell loss, and adverse events. RESULTS: Fifty eyes of 26 patients with a mean age of 22.73 ± 3.74 years were included. A significant improvement in UDVA from baseline (logarithm of the minimum angle of resolution [logMAR] 0.63 ± 0.25) was noted at the 3-month (logMAR 0.08 ± 0.15) and 6-month (logMAR 0.13 ± 0.18) follow-up visits (P < .001). Significant keratometric flattening from baseline was noted at all follow-up visits (P < .001). No significant endothelial cell loss or adverse effects were noted. A significant correlation was noted between the change in MRSE and preoperative corneal biomechanics (deformation amplitude ratio, P = .029). CONCLUSIONS: Transepithelial PiXL with supplemental oxygen might be a safe and effective approach for reduction of myopia. The change in MRSE and keratometric flattening was greater in comparison with earlier protocols, including the epithelium-off approach.

Tuina for children with myopia: A protocol for a systematic review.

BACKGROUND: The study aims to evaluate the effectiveness and safety of Tuina for children with myopia. METHODS: The following electronic databases will be searched from establishment to July 2019: Cochrane Library, MEDLINE, EMBASE, Web of Science, Springer, World Health Organization International Clinical Trials Registry Platform (ICTRP), China National Knowledge Infrastructure (CNKI), Wan-fang database, Chinese Scientific Journal Database (VIP), Chinese Biomedical Literature Databases (CBM), and other databases. All published randomized controlled trials (RCTs) about this topic will be included. Two independent researchers will operate article retrieval, duplication removing, screening, quality evaluation, and data analyses by Review Manager (V.5.3.5). Meta-analyses, subgroup analysis, and/or descriptive analysis will be performed based on the included data conditions. RESULTS: High-quality synthesis and/or descriptive analysis of current evidence will be provided from improvement of distant vision, improvement of myopic diopter, and side effects. CONCLUSION: This study will provide the evidence of whether Tuina is an effective and safe intervention for children with myopia. PROSPERO REGISTRATION NUMBER: CRD42019142283.

Current and emerging pharmaceutical interventions for myopia.

Myopia is a major cause of visual impairment. Its prevalence is growing steadily, especially in East Asia. Despite the immense disease and economic burden, there are currently no Food and Drug Administration-approved drugs for myopia. This review aims to summarise pharmaceutical interventions of myopia at clinical and preclinical stages in the last decade and discuss challenges for preclinical myopia drugs to progress to clinical trials. Atropine and oral 7-methylxanthine are shown to reduce myopia progression in human studies. The former has been extensively studied and is arguably the most successful medication. However, it has side effects and trials on low-dose atropine are ongoing. Other pharmaceutical agents being investigated at a clinical trial level include ketorolac tromethamine, oral riboflavin and BHVI2 (an experimental drug). Since the pathophysiology of myopia is not fully elucidated, numerous drugs have been tested at the preclinical stage and can be broadly categorised based on the proposed mechanisms of myopisation, namely antimuscarinic, dopaminergic, anti-inflammatory and more. However, several agents were injected intravitreally or subconjunctivally, hindering their progress to human trials. Furthermore, with atropine being the most successful medication available, future preclinical interventions should be studied in combination with atropine to optimise the treatment of myopia.

Hydrogel Contact Lens Water Content is Dependent on Tearfilm pH.

Introduction: Based on clinical inferences, investigators theorized in situ soft lens hydration was linked to the precorneal tearfilm pH. Methods: Forty-one myopic subjects at Fort Rucker, AL, USA were fitted with one of two types of extended-wear soft contact lenses, and were followed quarterly for a period of 33 mo. The anterior soft contact lens surface pH was measured in situ, while the in vitro lens water content was measured immediately after lens removal, using a hand-held refractometer on one lens, and a gravimetric means of hydration measurement on the other lens. Results: The in situ pH increased logarithmically across extended wearing time, reaching an asymptote at approximately 5 d' wearing time at a pH of 7.45 ± 0.03. Lens water content was shown to similarly decrease at an inversely logarithmic rate, leveling off at 4-5 d' extended wearing time. Both means of hydration assessment correlated well with each other across days' extended wearing time (R = 0.98; p < 0.0001). Discussion: A log-log dual conversion yielded significantly different linear slopes (p < 0.001), based on a multifactorial analysis of both lens types, by the pH, and by their water content. The differing ionic status of each material accentuated their varied polar attraction characteristics. Two soft lenses, identical in all patient-based parameters, could provide differing oxygen availability, as well as differing physical fits in patients of identical physical characteristics, as a result of their unique tearfilm pH differences. Conclusion: The in situ hydrogel lens water content is directly dependent on the precorneal tearfilm pH.

Diminuição da progressão da miopia com atropina 0, 025% / Decrease of myopia progression with 0. 025% atropine

Resumo Objetivo: Demonstrar a eficácia do uso do colírio de atropina 0,025% em crianças míopes, no Brasil, para a diminuição da progressão da miopia. Métodos: Realizou-se estudo prospectivo em 60 pacientes do Hospital Geral Universitário e Oftalmocenter Santa Rosa - Cuiabá - MT, com idades entre 6 e 12 anos, com equivalente esférico da refração entre -1,00 a -6,00 DE, refração cilíndrica < -1,00 DC e taxa de progressão anual de 0,50 DE (ou maior). Efetuou-se exame oftalmológico geral, topografia corneana e a medida do diâmetro anteroposterior do globo ocular (DAP). Os pacientes foram divididos em dois grupos: em que o Grupo 1 recebeu colírio de atropina 0,025%, todas as noites, e prescreveu-se a refração total com lentes com antirreflexo de multicamadas; e, no Grupo 2, somente a refração total. Nova avaliação foi realizada dois anos após. O teste T Student pareado foi utilizado para comparações das refrações, DAP e ceratometrias, medidas no exame inicial e no exame com 2 anos de seguimento. Resultados: Das 60 crianças, 30 eram do Grupo 1 com idade média de 8,21 ± 1,72 anos, e as do grupo controle com idade média de 8,17 ± 1,73 anos. Quatorze (46,66%) e 16 (53,33%) eram do sexo masculino nos Grupos 1 e 2, respectivamente. O Grupo 1 revelou menor progressão da miopia (Grupo 1: 0,43 ± 0,19D, Grupo 2: 1,24 ± 0,37D) e menor crescimento do DAP em relação ao grupo controle (Grupo 1: 0,19 ± 0,09mm, Grupo 2: 0,48 ± 0,12mm). Houve diferença estatisticamente significativa (P<0,05) entre o grupo tratado e o controle em relação à refração e ao crescimento DAP. A topografia não teve mudança estatisticamente significativa. Conclusão: A atropina em baixas concentrações foi eficaz em diminuir a progressão da miopia em 65% desta população estudada, por 2 anos. No entanto estudos com maior número de participantes e em diversas regiões do Brasil poderiam demonstrar melhor esse fato.

Abstract Purpose: To demonstrate the efficacy of 0.025% atropine eyedrops in myopic children in Brazil for decreasing myopia progression Methods: This was a prospective study with 60 children from Hospital Geral Universitário and Oftalmocenter Santa Rosa in Cuiabá, MT, Brazil, aged between 6 to 12 years, with spherical equivalent refractive error of -1.00 to -6.00 diopters (D) and astigmatism of -1.00 D or smaller. They underwent a complete ophthalmological examination, corneal topography and optical biometry. Children were assigned into two groups: group 1 used 0.025% atropine drop, once-nightly dosing, and it was prescribed total refraction in anti-reflective coating lens; and group 2 was prescribed just total refraction. A new evaluation was conducted 2 years after that. Paired student's t-test was used to compare refractions, axial length and keratometry which were measured in an initial exam and after a two-year follow-up. Results: Of the 60 children, the 30 in group 1 had an age mean and SD 8.21 +/- 1.72, and of the control group were 8.17 +/- 1.73 years. Fourteen (46,66%) and 16 (53,33%) were male, respectively. Myopic progression was significantly lower in group 1 (-0.43 +/- 0.19 D) than in group 2 (-1.24 +/- 0.37 D) and axial length increase was also significantly smaller in group 1(0.19 +/- 0.09 mm) than in group 2 (0.48 +/- 0.12 mm). There were no significant statistical differences regarding keratometry between groups. Conclusions: Low dose atropine eyedrops were effective in decreasing myopia progression in 65% of this population studied for 2 years. Furthermore, a larger scale randomized controlled study with longer follow-up seems warranted.

Bilateral acute myopia and angle closure glaucoma induced by Ma-huang (Ephedra): A case report.

RATIONALE: Cases of bilateral acute angle closure have been reported after use of various drugs. PATIENT CONCERNS: A 52-year-old woman visited the emergency room and complained of acute bilateral ocular pain and decreased vision accompanied by headache, nausea, and vomiting. One day before, she had started a herbal medicine containing Ma-huang for weight loss. On examinations, myopic shift, edematous cornea, increased intraocular pressure, shallow anterior chamber, and thickened choroid on both eyes were observed. DIAGNOSES: Angle closure glaucoma induced by drug (Ma-huang). INTERVENTIONS: To promptly quit the offending drug and apply ocular hypotensives and cycloplegics. OUTCOMES: Her symptoms and signs were relieved after antiglaucoma medications and no significant recurrence has been occurred. LESSONS: Physicians prescribing weight loss medications containing Ma-huang must be aware of the potentially sight-threatening adverse effect of bilateral acute angle closure.

Effect of Bilberry Extract on Development of Form-Deprivation Myopia in the Guinea Pig.

PURPOSE: To investigate the effects of bilberry extract, Difrarel, on form-deprivation myopia in guinea pigs. METHOD: Thirty healthy pigmented guinea pigs, at the age of 3 weeks, were randomly assigned to 3 groups: 2 groups receiving daily orally administered Difrarel (300 mg/kg) either from the outset for 4 or 2 weeks after form deprivation and a control group. Form deprivation was induced with translucent eye patches on the right eye and lasted for 4 weeks. Another 12 guinea pigs without the form deprivation were assigned into 2 groups for oral administration of Difrarel and saline for 4 weeks. The refractive errors and axial length were measured in both eyes, and the posterior sclera was removed and assayed to evaluate the expressions of matrix metalloproteinase 2 (MMP2) and collagen I by a quantitative polymerase chain reaction and Western blot. RESULTS: Oral administration of Difrarel for 4 weeks was found to inhibit the axial elongation and decrease the myopic shift of refractive errors in the form-deprived eye. Upregulation of MMP2 and degradation of collagen I in the sclera of form-deprived eye were observed, and these were prevented by orally administered Difrarel. Moreover, oral administration of Difrarel had no effects on axial length, refractive errors, and the expression of MMP2 in the normal eye. CONCLUSION: This work demonstrates that orally administered Difrarel has an effect against form-deprivation myopia and raises the possibility that bilberry extracts or specific components might represent a useful treatment for preventing the progression of myopia in clinical practice.