A Phase I Clinical Study Comparing the Pharmacokinetics, Safety, and Immunogenicity of GB221 Injection and Trastuzumab (Herceptin®) in Healthy Chinese Adults.

BACKGROUND AND OBJECTIVE: GB221 is a recombinant humanized anti-HER2 monoclonal antibody. The purpose of this study was to evaluate the pharmacokinetic, safety, and immunogenicity of GB221 in healthy Chinese adults in comparison to trastuzumab (Herceptin®). METHODS: In this randomized, double-blind, parallel-group phase I clinical trial, 88 subjects were randomized 1:1 to receive a single intravenous infusion (90-100 min) of GB221 or trastuzumab (6 mg/kg). The primary pharmacokinetic parameters-maximum observed serum concentration (Cmax), area under the serum concentration-time curve from zero to the last quantifiable concentration at time t (AUC0-t), and area under the serum concentration-time curve from time zero to infinity (AUC0-∞)-of GB221 and trastuzumab were compared to establish whether the 90% confidence interval (CI) attained the 80-125% bioequivalence standard. Safety and immunogenicity were also evaluated. RESULTS: The GB221 group (n = 43) and the trastuzumab group (n = 44) showed similar pharmacokinetic characteristics. The geometric mean ratios (90% CI) of Cmax, AUC0-t, and AUC0-∞ between the two groups were 107.53% (102.25-113.07%), 108.31% (103.57-113.26%), and 108.34% (103.57-113.33%), respectively. The incidence of treatment-emergent adverse events (TEAEs) was 83.7% (36/43) of the subjects in the GB221 group and 95.5% (42/44) of the subjects in the trastuzumab group. No subjects withdrew from the trial due to TEAEs, and there were no occurrences of serious adverse events. All subjects tested negative for antidrug antibodies (ADA). CONCLUSION: GB221 demonstrated similar pharmacokinetics to trastuzumab and comparable safety and immunogenicity in healthy Chinese adults.

First-in-human trial of SAR107375E, a novel small molecule anticoagulant with dual inhibition of factor Xa and factor IIa.

BACKGROUND: SAR107375E is a direct dual inhibitor of both Factor Xa and Factor IIa and has shown potent anticoagulation activity in vitro and animals. This study evaluated the safety, tolerability, pharmacokinetics, and pharmacodynamics of single ascending intravenous doses of SAR107375E in healthy Chinese adult subjects. METHODS: In this randomized, double-blind, placebo-controlled trial, 60 healthy Chinese adult subjects were administered intravenously single ascending doses (0.5, 1.5, 3.0, 5.0, 7.5, 10.0, 15.0, or 20.0 mg) of SAR107375E (N = 44) or placebo (N = 16). Plasma and urine concentrations of SAR107375E were measured and used to calculate pharmacokinetic parameters. Coagulation functions were measured and compared with baseline values. Treatment-emergent adverse events were recorded to evaluate safety. RESULTS: In plasma, from the 0.5 to 20.0 mg dose group, t1/2 is 1.51-4.00 h, Cmax is 59.05-1360 ug/L, and AUC0-t is 25.01-528.45 h*ug/L. And it shows dose proportionality in the 5.0-20.0 mg range. Activated partial thromboplastin time and Ecarin clotting time correlated linearly with drug plasma concentration. No serious adverse events were reported during the study. CONCLUSION: SAR107375E exhibits good safety and tolerability, predictable pharmacokinetics and pharmacodynamics. CLINICAL TRIAL REGISTRATION: www.chinadrugtrials.org.cn, identifier is CTR20211082.

Phase I, Randomized, Placebo-Controlled, Dose-Escalation Study of GB223, a Fully-Humanized Monoclonal Antibody to RANKL, in Healthy Chinese Adults.

BACKGROUND: GB223 is a novel, fully-humanized monoclonal antibody against the receptor activator of nuclear factor-kappa B ligand (RANKL). In this phase I study, the safety, tolerability, pharmacokinetics, pharmacodynamics, and immunogenicity of GB223 were investigated. PATIENTS AND METHODS: This was a randomized, double-blinded, placebo-controlled, single-dose escalation study conducted in 44 healthy Chinese adults. Participants were randomly assigned to receive a single subcutaneous injection dose of 7, 21, 63, 119, or 140 mg of GB223 (n = 34) or placebo (n = 10) and were followed up for 140-252 days. RESULTS: The results of noncompartmental analysis showed that GB223 was slowly absorbed after dosing, with a time to reach maximum concentration (Tmax) ranging from 5 to 11 days. Serum GB223 concentrations decreased slowly, with a long half-life ranging from 7.91 to 19.60 days. A two-compartment Michaelis-Menten model was found to best describe the pharmacokinetics of GB223, and the absorption rate of GB223 differed between males (0.0146 h-1) and females (0.0081 h-1). Serum C-terminal telopeptide of type I collagen decreased significantly postdose, and the inhibition lasted 42-168 days. No deaths or drug-related serious adverse events occurred. The most frequent adverse events were blood parathyroid hormone increased (94.1%), blood phosphorus decreased (67.6%) and blood calcium decreased (58.8%). In the GB223 group, 44.1% (15/34) of subjects were antidrug antibody positive after dosing. CONCLUSION: In this study, we demonstrated for the first time that a single subcutaneous injection of GB223, from 7 to 140 mg, is safe and well tolerated in healthy Chinese subjects. GB223 has a nonlinear pharmacokinetic profile, and sex was a potential covariate that may affect the absorption rate of GB223. CLINICAL TRIAL REGISTRATION: NCT04178044 and ChiCTR1800020338.

Investigation of Choroidal Blood Flow and Thickness Changes Induced by Near Work in Young Adults.

PURPOSE: This research aimed to determine the effects of near work on macular choroidal blood flow and thickness in young adults. METHODS: A total of 109 participants (19-28 years old) were recruited from Capital Medical University in China. The participants spent 40 min reading a book text at a distance of 33 cm. Swept-source optical coherence tomography/optical coherence tomography angiography (SS-OCT/OCTA) was performed to measure the changes in choriocapillaris perfusion area (CCPA) and choroidal thickness (ChT) after 40 min of near work. The SS-OCT/OCTA data covered an area of 6 mm × 6 mm, which centered on the fovea. RESULTS: The baseline ChT and CCPA before near work were negatively correlated with AL, while positively correlated with the magnitude of spherical equivalent (p < .001). Total CCPA decreased significantly by 6 mm × 6 mm macular area after near work compared to that before near work (24.26 ± 1.96 vs. 24.63 ± 1.61 mm2, p<.001). The macular ChT was lower after 40 min of reading than that before 40 min of reading, but no significant difference was observed (302.25 ± 77.69 vs. 304.92 ± 79.73 µm, p = .078). The extent of choroidal thinning was significantly positively correlated with the magnitude of CCPA reduction (p < .001). The decline in CCPA after near work was significantly positively correlated with axial length (AL; p < .001). CONCLUSION: This study demonstrated that near work significantly decreased CCPA. The extent of CCPA reduction after near work was associated with higher severity of myopia and choroidal thinning. The baseline CCPA and ChT decreased gradually with AL.

Biosimilarity Assessment of the Biosimilar Teriparatide Candidate and the Reference Drug in Healthy Subjects.

SAL001, a recombinant form of parathyroid hormone, is a biosimilar drug to teriparatide and is planned to be used in osteoporosis treatment. A single-dose, randomized, open-label, 2-way crossover trial was conducted in healthy subjects to compare the pharmacokinetics (PK) and safety between SAL001 and the reference drug. Sixty-four subjects were enrolled in the study, and 61 subjects completed the study. In each period, 20 µg of the test or reference formulation was administered subcutaneously. SAL001 was administered by autoinjector pen, whereas the reference drug was administered by a self-matched injection pen. Serial blood samples were obtained for the analyses of PK and serum calcium concentration. Geometric mean ratios with 90%CIs for the maximum plasma concentration (Cmax ) and area under the plasma concentration-time curve (AUC) were estimated. The safety of these 2 formulations was also evaluated. Overall, the 90%CIs for the geometric mean ratios of Cmax , AUC from time 0 to the last quantifiable time point, and AUC from time 0 extrapolated to infinity of the test or reference product were within 80.0%-125.0% of biosimilarity criteria. Other PK parameters, serum calcium concentration, and safety profiles had no significant differences between the 2 formulations. SAL001 demonstrated PK similarity to the reference drug, and the serum calcium concentration and safety profiles of SAL001 were also considered comparable to the reference drug.

Effect of Atropine 0.01% Eye Drops on the Difference in Refraction and Axial Length between Right and Left Eyes.

INTRODUCTION: This study sought to determine whether the application of 0.01% atropine eye drops could impact the disparity in refraction and axial length (AL) between the right and left eyes in Chinese children. METHODS: The study was designed as a double-blind, placebo-controlled randomized trial. A total of 220 children aged 6-12 years were recruited from the Beijing Tongren Hospital in Beijing, China. Participants were randomized in a 1:1 ratio and were prescribed 0.01% atropine or placebo eye drops to be administered once a night to both eyes for the duration of 1 year. The cycloplegic refraction and AL were recorded including baseline, 6 months, and again at the 12 months. RESULTS: After 1-year follow-up period, 76 (69%) and 83 (75%) subjects of the initial 220 participants were identified as the 0.01% atropine and placebo groups, respectively. The inter-ocular difference in spherical equivalent refraction (SER) and AL demonstrated stable values in the 0.01% atropine treatment group (SER: p = 0.590; AL: p = 0.322) analyzed after 1 year, but found a significant increase (SER: p < 0.001; AL: p = 0.001) in the placebo group. Furthermore, over 1 year, eyes with greater myopia in the atropine group exhibited slower myopia progression (0.45 ± 0.44 D) than the lesser myopic eye (0.56 ± 0.44 D) (p = 0.003). CONCLUSION: This study demonstrated that 0.01% atropine could maintain the inter-ocular SER and AL difference. And 0.01% atropine appeared to be more effective in delaying the progression of myopia in eyes with more myopia than in the less myopic eyes.

The effect of atropine 0.01% eyedrops on relative peripheral refraction in myopic children.

BACKGROUND: Relative peripheral refraction (RPR) is a significant factor that participates in myopic development. Here, we evaluated the effects of atropine 0.01% eyedrops, as an antimyopia drug, on RPR. METHODS: Seventy-three children were enrolled from a randomized, double-blinded, placebo-0.01% atropine eyedrops cross-over trial. The study group had used the placebo for one year and then crossed over to atropine 0.01% eyedrops for half a year. The control group had used 0.01% atropine for one year and then crossed over to placebo eyedrops for half a year. Central and horizontal peripheral refractions (15° and 30° at the temporal and nasal retina) were measured under non-cycloplegia and cycloplegia. RESULTS: No significant differences in age, gender, and central refraction were identified between the two groups (P > 0.05). Under non-cycloplegia, the control group showed significant relative hyperopia in the temporal 30° retina and the nasal retina (P = 0.031; P < 0.001; P < 0.001). In the study group, the relative hyperopia in the temporal 30° retina disappeared (P = 0.983). After cycloplegia, the control group had less myopia in central refractions and less hyperopia in temporal RPR (P < 0.001; P = 0.039; P < 0.001). The study group did not present significant changes in central refractions and temporal RPR (P = 0.122; P = 0.222; P = 0.475). CONCLUSIONS: For myopic children, atropine 0.01% eyedrops can alleviate relative hyperopia in the temporal retina and the hyperopic shift before cycloplegia. The effect might participate in myopia control.

Effect of low-dose atropine eyedrops on pupil metrics: results after half a year of treatment and cessation.

PURPOSE: To evaluate the effect of low-dose atropine eyedrops on pupil metrics. METHODS: This study was based on a randomized, double-masked, placebo-controlled, and cross-over trial in mainland China. In phase 1, subjects received 0.01% atropine or placebo once nightly. After 1 year, the atropine group switched to placebo (atropine-placebo group), and the placebo group switched to atropine (placebo-atropine group). Ocular parameters were measured at the crossover time point (at the 12th month) and the 18th month. RESULTS: Of 105 subjects who completed the study, 48 and 57 children were allocated into the atropine-placebo and placebo-atropine groups, respectively. After cessation, the photopic pupil diameter (PD) and mesopic PD both decreased (- 0.46 ± 0.47 mm, P < 0.001; - 0.30 ± 0.74 mm, P = 0.008), and the constriction ratio (CR, %) increased (4.39 ± 7.54, P < 0.001) compared with values at the crossover time point of the atropine-placebo group; pupil metrics of the atropine-placebo group had no difference from the values at the crossover time point of the placebo-atropine group. After 6 months of treatment, the photopic PD and the mesopic PD increased (0.54 ± 0.67 mm, P < 0.001; 0.53 ± 0.89 mm, P < 0.001), the CR (%) decreased (- 2.53 ± 8.64, P < 0.001) compared with values at the crossover time point of the placebo-atropine group. There was no significant relationship between pupil metrics and myopia progression during 0.01% atropine treatment. CONCLUSION: Pupil metrics and the CR could return to pre-atropine levels after cessation. Pupil metrics had no significant effect on myopia progression during treatment.

Myopia progression after cessation of low-dose atropine eyedrops treatment: A two-year randomized, double-masked, placebo-controlled, cross-over trial.

PURPOSE: The purpose of the study was to evaluate myopia progression and axial elongation after stopping 0.01% atropine eye drops through a 2-year cross-over study. METHODS: This study was a randomized, double-masked, placebo-controlled, cross-over trial in mainland China. 220 children aged 6-12 years with spherical equivalent range of -1.00 D to -6.00 D in both eyes were enrolled in Phase 1 for 1 year. Children who had completed the first year's follow-up continued in the second phase. In Phase 2, the placebo group was crossed over to the 0.01% atropine group (referred to as the 'placebo-atropine group'), and the 0.01% atropine group was crossed over to the placebo group (referred to as the 'atropine-placebo group'). All children underwent the examination of cycloplegic refraction and axial length at a 6-month interval. Only data from right eyes were included in analysis. RESULTS: One hundred thirty-three subjects completed 2 years of follow-up. In the first year, the mean myopia progression in atropine-placebo group was 0.21 ± 0.08 D slower than that in placebo-atropine group. After cross-over treatment, the mean myopia progression in atropine-placebo group was 0.22 ± 0.07D faster than that in placebo-atropine group in the second year. Over 2 years, the mean myopia progression was -1.26 ± 0.66D and -1.25 ± 0.70D in the atropine-placebo and placebo-atropine groups (p = 0.954). CONCLUSIONS: The difference in myopia progression between atropine-placebo group and placebo-atropine group in Phase 1 was similar to Phase 2 during the cross-over treatment. Through our cross-over trial, the results suggest that there is no rebound effect after using 0.01% atropine eye drops to prevent progression of myopia.

Effect of 0.01% atropine eyedrops on intraocular pressure in schoolchildren: a randomized clinical trial.

AIM: To assess the effect of 0.01% atropine eye drops on intraocular pressure (IOP) in myopic children. METHODS: A placebo-controlled, double-masked, randomized study. Totally 220 children aged 6 to 12y with myopia ranging from -1.00 to -6.00 D in both eyes were enrolled. Children were randomized in a 1:1 ratio to either 0.01% atropine eye drops or a placebo group using generated random numbers. All participants underwent the examination of IOP and cycloplegic refraction at baseline, 6 and 12mo. The change of IOP and the proportion of subjects with increased IOP in atropine and placebo groups were compared. RESULTS: Of 220 children, 117 were boys (53.2%). A total of 159 (72.3%) participants completed the follow-up at the 1-year study. At baseline, the mean IOP was 15.74 mm Hg (95%CI, 15.13 to 16.34 mm Hg) for the 0.01% atropine group and 15.59 mm Hg (95%CI, 15.00 to 16.19 mm Hg) for placebo group (mean difference, 0.14 mm Hg; P=0.743) after adjusting for central corneal thickness at baseline. At one year follow-up, the mean change of IOP was 0.16 mm Hg (95%CI, -0.43 to 0.76 mm Hg) for the 0.01% atropine group and -0.11 mm Hg (95%CI, -0.71 to 0.50 mm Hg) for placebo group (mean difference, 0.27 mm Hg; P=0.525) after adjusting for central corneal thickness. The 51.4% of children have increased IOP in the 0.01% atropine group, compared with 45.9% in the placebo group (P=0.511). CONCLUSION: The 0.01% atropine eye drops do not significantly affect the risk of elevated IOP. It is relatively safer to use in the studies that try to minimize myopia progression. However, a further long-duration study is required to be validated.

Brain Activation Induced by Myopic and Hyperopic Defocus From Spectacles.

Purpose: To assess neural changes in perceptual effects induced by myopic defocus and hyperopic defocus stimuli in ametropic and emmetropic subjects using functional magnetic resonance imaging (fMRI). Methods: This study included 41 subjects with a mean age of 26.0 ± 2.9 years. The mean spherical equivalence refraction was -0.54 ± 0.51D in the emmetropic group and -3.57 ± 2.27D in the ametropic group. The subjects were instructed to view through full refractive correction, with values of +2.00D to induce myopic defocus state and -2.00D to induce hyperopic defocus state. This was carried over in three random sessions. Arterial spin labeling (ASL) perfusion was measured using fMRI to obtain quantified regional cerebral blood flow (rCBF). Behavioral tests including distant visual acuity (VA) and contrast sensitivity (CS), were measured every 5 min for 30 min. Results: Myopic defocus induced significantly greater rCBF increase in four cerebral regions compared with full correction: right precentral gyrus, right superior temporal gyrus, left inferior parietal lobule, and left middle temporal gyrus (P < 0.001). The differences were less significant in low myopes than emmetropes. In the hyperopic defocus session, the increased responses of rCBF were only observed in the right and left precentral gyrus. Myopic defocused VA and CS improved significantly within 5 min and reached a plateau shortly after. Conclusion: This study revealed that myopic defocus stimuli can significantly increase blood perfusion in visual attention-related cerebral regions, which suggests a potential direction for future investigation on the relationship between retinal defocus and its neural consequences.

NLRP3 gene polymorphisms and expression in rheumatoid arthritis.

The present study aimed to investigate the association between the single-nucleotide polymorphisms (SNPs) rs4612666 and rs10754558 in the NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) gene and the susceptibility to rheumatoid arthritis (RA) in a Han Chinese population. mRNA expression of NLRP3, apoptosis-associated speck-like protein (ASC), and caspase-1 were determined in peripheral blood mononuclear cells (PBMCs) and neutrophils using reverse-transcription quantitative PCR. The results demonstrated that the C allele at rs4612666 locus and the G allele at rs10754558 locus were associated with significantly increased risk of RA. A statistical significance was also revealed in the dominant model (CC+CT vs. TT: OR=1.549; 95% CI=1.120-2.144; and GG + GC vs. CC: OR=2.000; 95% CI=1.529-2.616; P<0.05). Additionally, the mRNA expression of NLRP3, ASC and caspase-1 in PBMCs and neutrophils derived from patients with RA were significantly upregulated compared with the controls. Furthermore, the mRNA levels of NLRP3, ASC and caspase-1 in PBMCs and neutrophils from patients with active RA were notably increased compared with patients in remission. NLRP3 expression was positively correlated with the levels of C-reaction protein, erythrocyte sedimentation rate and disease activity score of 28 joint counts. Overall, the current study indicated that the NLRP3 rs4612666 and rs10754558 loci were associated with susceptibility to RA. In addition, the results of the present study demonstrated that the high expression of NLRP3 could serve a critical role in the pathogenesis of RA.

Effect of reading with a mobile phone and text on accommodation in young adults.

PURPOSE: To investigate the effects of reading with mobile phone versus text on accommodation accuracy and near work-induced transient myopia (NITM) and its subsequent decay during near reading in young adults with mild to moderate myopia. METHODS: The refractions of 31 young adults were measured with an open-field autorefractor (WAM-5500, Grand Seiko) for two reading tasks with a mobile phone and text at 33 cm. The mean age of the young adults was 24.35 ± 1.80 years. The baseline refractive aspects were determined clinically with full distance refractive correction in place. The initial NITM and its decay time and accommodative lag were assessed objectively immediately after binocularly viewing a mobile phone or text for 40 min. RESULTS: The mean ± standard deviation (SD) initial NITM magnitude was greater for reading with text (0.23 ± 0.26 D) than for reading with mobile phone (0.12 ± 0.17 D), but there was no significant difference between the two reading tasks (p = 0.082). The decay time (median, first quartile, and third quartile) was 60 s (16, 154) and 70 s (32, 180) in the phone task and text task groups, respectively. There was also no significant difference in the decay time between the two reading types in general (p = 0.294). The accommodative lags of text tasks and mobile phones tasks were equivalent (1.27 ± 0.52 D vs 1.31 ± 0.64 D, p = 0.792). CONCLUSION: There were no significant differences in accommodative lags and the initial NITM and its decay time between reading with a mobile phone and text in young adults.

Prevalence and risk factors of pseudomyopia in a Chinese children population: the Anyang Childhood Eye Study.

AIMS: To investigate the prevalence and predictors of pseudomyopia in Chinese children and its association with myopia progression. METHODS: A prospective, school-based, cohort study of 6- and 13-year-old children was conducted in Anyang, China. Pre-cycloplegic and post-cycloplegic autorefraction were performed at baseline and 1 year later. Pseudomyopia was defined as spherical equivalent refractive (SER) error in the better-seeing eye ≤-0.50 D before cycloplegia and >-0.50 D after cycloplegia. Among pseudomyopic children, pseudomyopic power was defined as non-cycloplegic SER subtracted from cycloplegic SER. Market survey was collected in all optometry stores in Anyang city to investigate how cycloplegia is used for refracting children. RESULTS: A total of 2612 children aged 6 years and 1984 children aged 13 years were included. Of the two cohorts, median cycloplegic SER (IQR) was 1.00 D (0.50, 1.38) and -1.13 D (-2.63, 0.13) respectively, myopia prevalence was 5.2% and 61.0%, pseudomyopia prevalence was 24.1% and 18.9%, and median pseudomyopic power was 1.13 D (0.63, 1.63) and 0.38 D (0.13, 0.88). In both cohorts, greater baseline hyperopia was the strongest predictor of pseudomyopia (p<0.001), whereas time spent on near work was not associated with pseudomyopic power (p>0.05). After 1 year, 15.6% (98/629) of 6-year-olds and 10.7% (40/374) of 13-year-olds with pseudomyopia developed myopia. Compared with myopes, pseudomyopic children with the same pre-cycloplegic SER had slower myopic progression (p<0.001). Among all 127 optometry stores in Anyang, only 4 (3.15%) used cycloplegia for refracting children. CONCLUSION: Pseudomyopia is more prevalent in younger, more hyperopic children. Pseudomyopia is not an independent risk factor for myopic progression in this setting.

Design, synthesis and antitumor evaluation of novel 5-methylpyrazolo[1,5-a]pyrimidine derivatives as potential c-Met inhibitors.

A series of novel 5-methylpyrazolo[1,5-a]pyrimidine derivatives (10a-10x) were designed, synthesized, and evaluated for their in vitro inhibitory activities against c-Met kinase and antiproliferative activities against the SH-SY5Y, MDA-MB-231, A549, and HepG2 cell lines. Most of the compounds remarkably inhibited c-Met kinase and showed moderate to good cytotoxicity and selectivity toward the four cancer cell lines. Among them, compounds 10b and 10f were the two most potent selective c-Met inhibitors with half-maximal inhibitory concentration (IC50) values of 5.17 ± 0.48 nM and 5.62 ± 0.78 nM, respectively, and suppression abilities comparable with the positive control cabozantinib. Cell proliferation assay further demonstrated that the two most promising compounds 10a and 10b also showed good cytotoxicity and selectivity toward MDA-MB-231 cells, with IC50 values of 26.67 ± 2.56 µM and 26.83 ± 2.41 µM, respectively. Compounds 10f and 10g showed cytotoxicity and selectivity toward A549 cells, with IC50 values of 20.20 ± 2.04 µM and 21.65 ± 1.58 µM, respectively. All antiproliferative activities were within the range of those of cabozantinib. Notably, these compounds presented relatively low hepatotoxicity compared with reference drugs. Moreover, the preliminary structure-activity relationship and docking studies revealed that replacement of a nitrogen-containing heterocycle on the R2 (block A) group might improve the c-Met kinase inhibitory and antiproliferative effects in MDA-MB-231 cells, whereas displacement by a substituted benzene ring, especially for the p-fluorophenyl or 4-fluoro-3-methoxyphenyl moiety, on the R2 group enhanced cytotoxicity toward A549 cells. Together, these results suggest that 10b and 10f are promising compounds and provide a basis for their development as new antitumor agents.

Ab interno vs ab externo microcatheter-assisted trabeculotomy for primary congenital glaucoma with clear cornea.

IMPORTANCE: This is the first comprehensive comparison between ab interno approach and ab externo approach for microcatheter-assisted trabeculotomy in primary congenital glaucoma with clear cornea. BACKGROUND: Ab externo microcatheter-assisted trabeculotomy is considered to be the gold standard for primary congenital glaucoma. The novel ab interno approach would intuitively be similar to ab externo approach for microcatheter-assisted trabeculotomy in eyes with clear cornea; however, there is no evidence yet. DESIGN: Non-contemporary comparison of retrospective case series. PARTICIPANTS: Fifty-eight and fifty-seven consecutive primary congenital glaucoma eyes with clear corneas underwent ab interno and ab externo microcatheter-assisted trabeculotomy, respectively. METHODS: Retrospective comparison of clinical outcomes. MAIN OUTCOME MEASURES: Surgical success was defined as a postoperative intraocular pressure of ≤21 mmHg with at least a 30% reduction from preoperative IOP with or without the use of anti-glaucoma medication (qualified and complete success, respectively). RESULTS: The qualified success rate (87.9% vs 82.2%, P = .40) and complete success rates (81.0% vs 73.3%, P = .32) were comparable between groups. Complications were minimal and comparable. Less than 360° trabeculotomy (P = .009) and a higher number of previous surgeries (P = .03) were both associated with worse surgical outcomes. CONCLUSIONS AND RELEVANCE: Ab interno approach provide good and comparable outcomes as ab externo approach for microcatheter-assisted trabeculotomy in primary congenital glaucoma eyes with clear cornea. It should be considered as the initial choice in these patients with the benefit of sparing conjunctiva. Successful trabeculotomy with either technique during the first attempt is critical to overall success and underscores the need for proficiency before independent practice.

Safety and Efficacy of Low-Dose Atropine Eyedrops for the Treatment of Myopia Progression in Chinese Children: A Randomized Clinical Trial.

Importance: Because studies have suggested that atropine might slow the progression of myopia in children, randomized clinical trials are warranted to understand this potential causal relationship. Objective: To evaluate the efficacy and safety of atropine, 0.01%, eyedrops on slowing myopia progression and axial elongation in Chinese children. Design, Setting, and Participants: This was a randomized, placebo-controlled, double-masked study. A total of 220 children aged 6 to 12 years with myopia of -1.00 D to -6.00 D in both eyes were enrolled between April 2018 and July 2018 at Beijing Tongren Hospital, Beijing, China. Cycloplegic refraction and axial length were measured at baseline, 6 months, and 12 months. Adverse events were also recorded. Interventions: Patients were randomly assigned in a 1:1 ratio to atropine, 0.01%, or placebo groups to be administered once nightly to both eyes for 1 year. Main Outcomes and Measures: Mean changes and percentage differences in myopia progression and axial elongation between atropine, 0.01%, or placebo groups. Results: Of 220 participants, 103 were girls (46.8%), and the mean (SD) age was 9.64 (1.68) years. The mean (SD) baseline refractive error and axial length were -2.58 (1.39) D and 24.59 (0.87) mm. Follow-up at 1 year included 76 children (69%) and 83 children (75%) allocated into the atropine, 0.01%, and placebo groups, respectively, when mean myopia progression was -0.49 (0.42) D and -0.76 (0.50) D in the atropine, 0.01%, and placebo groups (mean difference, 0.26 D; 95% CI, 0.12-0.41 D; P < .001), with a relative reduction of 34.2% in myopia progression. The mean (SD) axial elongation in the atropine, 0.01%, group was 0.32 (0.19) mm compared with 0.41 (0.19) mm in the placebo group (mean difference, 0.09 mm; 95% CI, 0.03-0.15 mm; P = .004), with relative reduction of 22.0% in axial elongation. Fifty-one percent and 13.2% of children progressed by at least 0.50 D and 1.00 D in the atropine, 0.01%, group, compared with 69.9% and 34.9% in the placebo group. No serious adverse events related to atropine were reported. Conclusions and Relevance: While the clinical relevance of the results cannot be determined from this trial, these 1-year results, limited by approximately 70% follow-up, suggest that atropine, 0.01%, eyedrops can slow myopia progression and axial elongation in children and warrant future studies to determine longer-term results and potential effects on slowing sight-threatening pathologic changes later in life. Trial Registration: http://www.chictr.org.cn Identifier: ChiCTR-IOR-17013898.

Visual Impairment and Spectacle Use in University Students in Central China: The Anyang University Students Eye Study.

PURPOSE: To investigate the prevalence and associations of visual impairment and spectacle use in university students in central China. DESIGN: Cross-sectional study. METHODS: This study included students aged 16-26 years in China. Study subjects from 2 universities underwent distance visual acuity (VA) assessment in both eyes with a logarithm of the minimum angle of resolution chart and their refractions were measured by cycloplegic autorefraction. Blindness was defined as presenting VA less than three-sixtieth in the better eye (World Health Organization definition), and visual impairment was defined as presenting VA less than six-twelfths. RESULTS: Overall, 9710 undergraduates were enumerated, 7704 (79.3%) subjects were included in this study. The prevalence of uncorrected VA less than six-twelfths and less than three-sixtieth in the better eye were 69.9% and 0.9%, respectively. Only 77.0% (4148/5388) of subjects with uncorrected VA in the better eye of less than six-twelfths wore glasses. For presenting VA, the prevalence of mild (VA <6/12 to 6/18), moderate (VA <6/18 to 6/60), and severe (VA <6/60 to 3/60) visual impairment was 6.3%, 11.2%, and 0.7%, respectively. Overall, 71.7% (4300/6001) of students with myopia (spherical equivalent ≤-0.5 diopters) wore spectacles. In multiple logistic regression analysis, visual impairment was associated with female sex (P < .001) and lower year level of education (P = .006) when presenting with VA. CONCLUSIONS: This study has documented a relatively high prevalence of visual impairment and relatively low spectacle coverage in Chinese university students. Given the potential impact of visual impairment, target education and accessible refraction services are highly important to solve the problem.

Synthesis and Evaluation of Novel Ligustrazine Derivatives as Multi-Targeted Inhibitors for the Treatment of Alzheimer's Disease.

A series of novel ligustrazine derivatives 8a⁻r were designed, synthesized, and evaluated as multi-targeted inhibitors for anti-Alzheimer's disease (AD) drug discovery. The results showed that most of them exhibited a potent ability to inhibit both ChEs, with a high selectivity towards AChE. In particular, compounds 8q and 8r had the greatest inhibitory abilities for AChE, with IC50 values of 1.39 and 0.25 nM, respectively, and the highest selectivity towards AChE (for 8q, IC50 BuChE/IC50 AChE = 2.91 × 106; for 8r, IC50 BuChE/IC50 AChE = 1.32 × 107). Of note, 8q and 8r also presented potent inhibitory activities against Aß aggregation, with IC50 values of 17.36 µM and 49.14 µM, respectively. Further cellular experiments demonstrated that the potent compounds 8q and 8r had no obvious cytotoxicity in either HepG2 cells or SH-SY5Y cells, even at a high concentration of 500 µM. Besides, a combined Lineweaver-Burk plot and molecular docking study revealed that these compounds might act as mixed-type inhibitors to exhibit such effects via selectively targeting both the catalytic active site (CAS) and the peripheral anionic site (PAS) of AChEs. Taken together, these results suggested that further development of these compounds should be of great interest.

Design, synthesis and evaluation of novel tacrine-multialkoxybenzene hybrids as multi-targeted compounds against Alzheimer's disease.

A series of benzoates (or phenylacetates or cinnamates) - tacrine hybrids (7a-o) were designed, synthesized and evaluated as multi-potent anti-Alzheimer drug candidates. The screening results showed that most of them exhibited a significant ability to inhibit ChEs, certain selectivity for AChE over BuChE and strong potency inhibitory of self-induced ß-amyloid (Aß) aggregation. All IC50 values of biological activity were at the nanomolar range. Especially, compound 7c displayed the greatest ability to inhibit AChE with an IC50 value of 5.63 nM and the highest selectivity with ratio of BuChE/AChE value of 64.6. Moreover, it also exhibited a potent inhibitory of Aß aggregation with an IC50 value of 51.81 nM. A Lineweaver-Burk plot and molecular modeling study showed that compound 7c targeted both the CAS and PAS of ChEs. A structure-activity relationship analysis suggested that the electron density of aromatic ring which was linked with tacrine through acetyl group played a significant role in determining the inhibitory activity.