Slit Guidance Ligand 3 (SLIT3) Loaded in Hydrogel Microparticles Enhances the Tendon-Bone Healing through Promotion of Type-H Vessel Formation: An Experimental Study in Mice.

Poor tendon-bone interface (TBI) integration is one of the major causes contributing to unsatisfactory healing quality in patients after anterior cruciate ligament (ACL) reconstruction. Type H vessels have been recently found to closely modulate bone formation via regulation of the osteo-angiogenic crosstalk, so the strategies favoring type H vessel formation may be promising therapeutic approaches for improved graft osteointegration. In this study, we reported for the first time the treatment outcome of slit guidance ligand 3 (slit3), a novel proangiogenic factor favoring type H vessel formation, in TBI healing in mice with ACL reconstruction. The mice (n = 87) were divided into three groups for various treatments: hydrogel microparticles (HMP, control group), slit3@HMP, and slit3 neutralizing antibody@HMP (slit3-AB@HMP). Histological analysis, gait performance, radiographic measurement, and biomechanical testing were performed to assess the TBI healing quality. Increased bony ingrowth and reduced fibrous scar tissue was formed at the TBI in the slit3@HMP group when compared to the HMP group. Meanwhile, the slit3-AB@HMP inhibited the osseous ingrowth and increased fibrous scar tissue formation relative to the HMP group. Compared to the HMP group, the slit3@HMP favored type H vessel formation at the TBI while the slit3-AB@HMP impeded it. According to micro-CT assessment, compared to the HMP group, the slit3@HMP significantly increased the peri-tunnel bone mass while the slit3-AB@HMP significantly reduced the peri-tunnel bone mass. The mice in the slit3@HMP group showed the best gait performance in terms of stance time, stride length, paw print area, and stance pressure. Dynamic laxity measurement and tensile testing showed the slit3@HMP group exhibited significantly reduced laxity displacement and improved failure load and stiffness relative to the other two groups. Collectively, the injection of slit3 could be used to enhance tendon-bone integration, which may be ascribed to modulation of angiogenesis-osteogenesis crosstalk coupled by type H vessels.

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.

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.

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.

Association Between Color Vision Deficiency and Myopia in Chinese Children Over a Five-Year Period.

Purpose: To explore the relationship of color vision deficiency with myopia progression and axial elongation in Chinese primary school children during a five-year cohort study. Methods: A total of 2849 grade 1 students (aged 7.1 ± 0.4 years) from 11 primary schools were enrolled and followed up for five years. Cycloplegic autorefraction and axial length were measured annually. Color vision testing was performed using Ishihara's test and the City University color vision test. Results: The prevalence of color vision deficiency was 1.68%, with 2.81% in boys and 0.16% in girls. Color-deficient cases consisted of 91.6% deutan and 8.3% protan. Over the five years, the cumulative incidence of myopia was 35.4% (17/48) in the color-vision deficiency group, which was lower than the 56.7% (1017/1794) in the color normal group (P = 0.004). Over the five-year study period, the change in spherical equivalent refraction in the color vision-deficiency group (-1.81 D) was also significantly lower than that in the color normal group (-2.41 D) (P = 0.002). Conclusions: The lower incidence and slower progression of myopia in children with color-vision deficiency over the five-year follow-up period suggest that color-deficient individuals are less susceptible to myopia onset and development.