Metabolomic profiling of the aqueous humor in patients with pediatric cataract.

Pediatric cataract, including congenital and developmental cataract, is a kind of pediatric vision-threatening disease with extensive phenotypic heterogeneity and multiple mechanisms. We aimed to investigate the metabolite profile of aqueous humor (AH) in patients with pediatric cataracts, and identify underlying mutual correlations between differential metabolites. Metabolomic profiles of AH were analyzed and compared between pediatric cataract patients (n = 33) and age-related cataract patients without metabolic diseases (n = 29), using global untargeted metabolomics with ultra-high-performance liquid chromatography tandem mass spectrometry. Principal component analysis, partial least squares discriminant analysis and heat map were applied. Enriched pathway analysis was conducted using Kyoto Encyclopedia of Genes and Genomes. Receiver-operating characteristic (ROC) analyses were employed to select potential biomarkers. A total of 318 metabolites were identified, of which 54 differential metabolites (25 upregulated and 29 downregulated) were detected in pediatric cataract group compared with controls (variable importance of projection >1.0, fold change ≥1.5 or ≤ 0.667 and P < 0.05). A significant accumulation of N-Acetyl-Dl-glutamic acid was observed in pediatric cataract group. The differential metabolites were mainly enriched in histidine metabolism (increased L-Histidine and decreased 1-Methylhistamine) and the tryptophan metabolism (increased N-Formylkynurenine and L-Kynurenine). 5-Aminosalicylic acid showed strong positive mutual inter-correlation with L-Tyrosinemethylester and N,N-Diethylethanolamine, both of which were down-regulated in pediatric cataract group. The ROC analysis implied 11 metabolites served as potential biomarkers for pediatric cataract patients (all area under the ROC curve ≥0.900). These results illustrated novel potential metabolites and metabolic pathways in pediatric cataract, which provides new insights into the pathophysiology of pediatric cataract.

Effect of Posterior Keratometry on the Accuracy of 10 Intraocular Lens Calculation Formulas: Standard Keratometry versus Total Keratometry.

PURPOSE: To investigate the effect of posterior keratometry (PK) on the accuracy of 10 intraocular lens (IOL) power calculation formulas using standard keratometry (K) and total keratometry (TK). METHODS: This is a retrospective consecutive case-series study. The IOL power was calculated using K and TK measured by IOLMaster 700 in 6 new-generation formulas (Barrett Universal II, Emmetropia Verifying Optical (EVO) 2.0, RBF Calculator 3.0, Hoffer QST, Kane, and Ladas Super Formula) and 4 traditional formulas (Haigis, Hoffer Q, Holladay 1, and SRK/T). The arithmetic prediction error (PE) and mean absolute PE (MAE) were evaluated. The locally-weighted scatterplot smoothing was performed to assess the relationship between PE and PK. RESULTS: A total of 576 patients (576 eyes) who underwent cataract surgery were included. Compared with using K, all formulas using TK showed a hyperopic shift in the whole group. Specifically, for eyes with PK exceeding -5.90 D, all formulas using TK exhibited a hyperopic shift (all P < 0.001), while eyes with PK less than -5.90 D showed a myopic shift (all P < 0.001). The MAE of new-generation formulas calculated with TK and K showed no statistical differences, while the MAE of traditional formulas with TK was larger (TK: 0.34 ~ 0.43 D; K: 0.33 ~ 0.42 D, all P < 0.05). CONCLUSIONS: The prediction bias of formulas with TK increased as PK deviated from -5.90 D. TK did not improve the prediction accuracy of new-generation formulas, and even performed worse in traditional formulas.

Lens regeneration using endogenous stem cells with gain of visual function.

The repair and regeneration of tissues using endogenous stem cells represents an ultimate goal in regenerative medicine. To our knowledge, human lens regeneration has not yet been demonstrated. Currently, the only treatment for cataracts, the leading cause of blindness worldwide, is to extract the cataractous lens and implant an artificial intraocular lens. However, this procedure poses notable risks of complications. Here we isolate lens epithelial stem/progenitor cells (LECs) in mammals and show that Pax6 and Bmi1 are required for LEC renewal. We design a surgical method of cataract removal that preserves endogenous LECs and achieves functional lens regeneration in rabbits and macaques, as well as in human infants with cataracts. Our method differs conceptually from current practice, as it preserves endogenous LECs and their natural environment maximally, and regenerates lenses with visual function. Our approach demonstrates a novel treatment strategy for cataracts and provides a new paradigm for tissue regeneration using endogenous stem cells.

Neutrophils promote tumor resistance to radiation therapy.

Nearly two-thirds of cancer patients are treated with radiation therapy (RT), often with the intent to achieve complete and permanent tumor regression (local control). RT is the primary treatment modality used to achieve local control for many malignancies, including locally advanced cervical cancer, head and neck cancer, and lung cancer. The addition of concurrent platinum-based radiosensitizing chemotherapy improves local control and patient survival. Enhanced outcomes with concurrent chemoradiotherapy may result from increased direct killing of tumor cells and effects on nontumor cell populations. Many patients treated with concurrent chemoradiotherapy exhibit a decline in neutrophil count, but the effects of neutrophils on radiation therapy are controversial. To investigate the clinical significance of neutrophils in the response to RT, we examined patient outcomes and circulating neutrophil counts in cervical cancer patients treated with definitive chemoradiation. Although pretreatment neutrophil count did not correlate with outcome, lower absolute neutrophil count after starting concurrent chemoradiotherapy was associated with higher rates of local control, metastasis-free survival, and overall survival. To define the role of neutrophils in tumor response to RT, we used genetic and pharmacological approaches to deplete neutrophils in an autochthonous mouse model of soft tissue sarcoma. Neutrophil depletion prior to image-guided focal irradiation improved tumor response to RT. Our results indicate that neutrophils promote resistance to radiation therapy. The efficacy of chemoradiotherapy may depend on the impact of treatment on peripheral neutrophil count, which has the potential to serve as an inexpensive and widely available biomarker.

[Research progress on camptothecin and its derivative nano-prodrugs based on tumor microenvironment response].

Nano-prodrug, one of the most widely used nano-formulation at present, has excellent efficacies in tumor treatment with high potential and clinical value. Camptothecin and its derivatives have broad prospects in the preparation of prodrugs for the treatment of tumors. Given the special microenvironment of tumors, including partial acidity, high concentration of reactive oxygen species, high concentration of glutathione and enzyme concentration, a large number of tumor microenvironment-responsive camptothecin and its derivative prodrugs were prepared. This paper classified them from the microenvironment response types and drug release characteristics, reviewed the research progress of camptothecin and its derivative prodrugs based on safety and clinical trials, and analyzed the existing problems and deficiencies, hoping to provide references for the development of camptothecin and its derivatives.

A Peer-to-Peer Live-Streaming Intervention for Children During COVID-19 Homeschooling to Promote Physical Activity and Reduce Anxiety and Eye Strain: Cluster Randomized Controlled Trial.

BACKGROUND: The COVID-19 pandemic has led to worldwide school closures, with millions of children confined to online learning at home. As a result, children may be susceptible to anxiety and digital eye strain, highlighting a need for population interventions. OBJECTIVE: The objective of our study was to investigate whether a digital behavior change intervention aimed at promoting physical activity could reduce children's anxiety and digital eye strain while undergoing prolonged homeschooling during the COVID-19 pandemic. METHODS: In this cluster randomized controlled trial, homeschooled grade 7 students at 12 middle schools in southern China were recruited through local schools and randomly assigned by the school to receive (1:1 allocation): (1) health education information promoting exercise and ocular relaxation, and access to a digital behavior change intervention, with live streaming and peer sharing of promoted activities (intervention), or (2) health education information only (control). The primary outcome was change in self-reported anxiety score. Secondary outcomes included change in self-reported eye strain and sleep quality. RESULTS: On March 16, 2020, 1009 children were evaluated, and 954 (94.5%) eligible children of consenting families were included in the intention-to-treat analysis. Children in the intervention (n=485, 6 schools) and control (n=469, 6 schools) groups were aged 13.5 (SD 0.5) years, and 52.3% (n=499) were male. The assigned interventions were completed by 896 children (intervention: n=467, 96.3%; control: n=429, 91.5%). The 2-week change in square-root-transformed self-reported anxiety scores was greater in the intervention (-0.23, 95% CI -0.27 to -0.20) vs control group (0.12, 95% CI 0.09-0.16; unadjusted difference -0.36, 95% CI -0.63 to -0.08; P=.02). There was a significant reduction in square-root-transformed eye strain in the intervention group (-0.08, 95% CI -0.10 to 0.06) compared to controls (0.07, 95% CI 0.05-0.09; difference -0.15, 95% CI -0.26 to -0.03; P=.02). Change in sleep quality was similar between the two groups. CONCLUSIONS: This digital behavior change intervention reduced children's anxiety and eye strain during COVID-19-associated online schooling. TRIAL REGISTRATION: ClinicalTrials.gov NCT04309097; http://clinicaltrials.gov/ct2/show/NCT04309097.

Cholesteric Molecular Tweezer Artificial Receptor for Rapid and Highly Selective Detection of Ag+ in Food Samples.

Chiral cholesteric molecular tweezer 7a was synthesized, and its recognition properties for Ag+, Al3+, Ca2+ etc., were investigated by UV and fluorescence spectra. The results showed that in ethanol/Tris (1/1, v/v, pH 7.0) buffer solution, the host molecular tweezer 7a had a specific recognition ability for Ag+, the detection limit was up to 1 × 10-6 mol/L, and other metal ions had little effect on Ag+ recognition. At the same time, the naked-eye detection of Ag+ was realized by the light red color of the complex solution. Furthermore, the mechanism of recognition of Ag+ by molecular tweezer 7a was studied by a nuclear magnetic titration test and computer molecular simulation, and a rapid detection method of Ag+ using host molecular tweezer 7a was established. Through the determination of Ag+ in milk powder, quinoa and other food samples, it was proved that this novel method had a good application prospect for the detection of Ag+ in food.

Shear-Thinning Viscous Materials for Subconjunctival Injection of Microparticles.

While drug-loaded microparticles (MPs) can serve as drug reservoirs for sustained drug release and therapeutic effects, needle clogging by MPs poses a challenge for ocular drug delivery via injection. Two polymers commonly used in ophthalmic procedures-hyaluronic acid (HA) and methylcellulose (MC)-have been tested for their applicability for ocular injections. HA and MC were physically blended with sunitinib malate (SUN)-loaded PLGA MPs for subconjunctival (SCT) injection into rat eyes. The HA and MC viscous solutions facilitated injection through fine-gauged needles due to their shear-thinning properties as shown by rheological characterizations. The diffusion barrier presented by HA and MC reduced burst drug release and extended overall release from MPs. The significant level of MP retention in the conjunctiva tissue post-operation confirmed the minimal leakage of MPs following injection. The safety of HA and MC for ocular applications was demonstrated histologically.

JNK1/ß-catenin axis regulates H2O2-induced epithelial-to-mesenchymal transition in human lens epithelial cells.

Epithelial-mesenchymal transition (EMT) is the main cause of fibrotic cataracts. Oxidative stress was recently shown to trigger epithelial-mesenchymal transition in human lens epithelial cells (hLECs). However, the underlying mechanism is not fully understood. Here we reported that exposure to low doses (100 µM) of H2O2 led to EMT in hLECs, as indicated by simultaneous down-regulated of E-cadherin and ZO-1, and up-regulated of alpha smooth muscle actin (α-SMA). H2O2-induced EMT was accompanied by accumulation of phosphorylated JNK1. In contrast, knockdown of JNK1 via siRNA reversed H2O2-induced EMT. Of interest, in human lens capsules of anterior subcapsule cataracts, the expressions of JNK1, as well as ß-catenin and its downstream effectors cyclin D and c-Myc, were augmented compared to that in normal lens capsules. Mechanistically, activated JNK1 dislodged ß-catenin from the cell membrane, which subsequently translocated to the nuclei and triggered transcription of its effectors. Nuclei ß-catenin, cyclin D and c-Myc were accumulated in H2O2-induced EMT and JNK1 depletion abrogated these trend in hLECs. In conclusion, our data suggest that JNK1 is essential for H2O2-induced EMT in hLECs via mediating the translocation of ß-catenin.

Prediction of myopia development among Chinese school-aged children using refraction data from electronic medical records: A retrospective, multicentre machine learning study.

BACKGROUND: Electronic medical records provide large-scale real-world clinical data for use in developing clinical decision systems. However, sophisticated methodology and analytical skills are required to handle the large-scale datasets necessary for the optimisation of prediction accuracy. Myopia is a common cause of vision loss. Current approaches to control myopia progression are effective but have significant side effects. Therefore, identifying those at greatest risk who should undergo targeted therapy is of great clinical importance. The objective of this study was to apply big data and machine learning technology to develop an algorithm that can predict the onset of high myopia, at specific future time points, among Chinese school-aged children. METHODS AND FINDINGS: Real-world clinical refraction data were derived from electronic medical record systems in 8 ophthalmic centres from January 1, 2005, to December 30, 2015. The variables of age, spherical equivalent (SE), and annual progression rate were used to develop an algorithm to predict SE and onset of high myopia (SE ≤ -6.0 dioptres) up to 10 years in the future. Random forest machine learning was used for algorithm training and validation. Electronic medical records from the Zhongshan Ophthalmic Centre (a major tertiary ophthalmic centre in China) were used as the training set. Ten-fold cross-validation and out-of-bag (OOB) methods were applied for internal validation. The remaining 7 independent datasets were used for external validation. Two population-based datasets, which had no participant overlap with the ophthalmic-centre-based datasets, were used for multi-resource validation testing. The main outcomes and measures were the area under the curve (AUC) values for predicting the onset of high myopia over 10 years and the presence of high myopia at 18 years of age. In total, 687,063 multiple visit records (≥3 records) of 129,242 individuals in the ophthalmic-centre-based electronic medical record databases and 17,113 follow-up records of 3,215 participants in population-based cohorts were included in the analysis. Our algorithm accurately predicted the presence of high myopia in internal validation (the AUC ranged from 0.903 to 0.986 for 3 years, 0.875 to 0.901 for 5 years, and 0.852 to 0.888 for 8 years), external validation (the AUC ranged from 0.874 to 0.976 for 3 years, 0.847 to 0.921 for 5 years, and 0.802 to 0.886 for 8 years), and multi-resource testing (the AUC ranged from 0.752 to 0.869 for 4 years). With respect to the prediction of high myopia development by 18 years of age, as a surrogate of high myopia in adulthood, the algorithm provided clinically acceptable accuracy over 3 years (the AUC ranged from 0.940 to 0.985), 5 years (the AUC ranged from 0.856 to 0.901), and even 8 years (the AUC ranged from 0.801 to 0.837). Meanwhile, our algorithm achieved clinically acceptable prediction of the actual refraction values at future time points, which is supported by the regressive performance and calibration curves. Although the algorithm achieved balanced and robust performance, concerns about the compromised quality of real-world clinical data and over-fitting issues should be cautiously considered. CONCLUSIONS: To our knowledge, this study, for the first time, used large-scale data collected from electronic health records to demonstrate the contribution of big data and machine learning approaches to improved prediction of myopia prognosis in Chinese school-aged children. This work provides evidence for transforming clinical practice, health policy-making, and precise individualised interventions regarding the practical control of school-aged myopia.

Interocular anatomical and visual functional differences in pediatric patients with unilateral cataracts.

BACKGROUND: Congenital cataracts are often complicated by anterior segment dysgenesis. This study aims to compare bilateral anterior segment parameters, macular thickness, and best-corrected visual acuity (BCVA) in pediatric cataract patients at 3 months after unilateral cataract extraction with intraocular lens implantation. METHODS: Fifty-three pediatric patients with uncomplicated unilateral total cataracts were included. At 3 months post-surgery, bilateral corneal thickness at the thinnest location (CTTL), anterior chamber depth (ACD), and anterior chamber volume (ACV) were measured using Pentacam. Central macular thickness (CMT) was evaluated using spectral-domain optical coherence tomography. BCVA was measured by experienced optometrists concurrently. Descriptive statistics and bivariate corrections were performed to analyze the interocular differences in bilateral anatomic parameters and their relationships with BCVA. RESULTS: For all 53 included patients (mean age 5.2 ± 2.3 years), the median BCVA was 10/40 in the operated eyes and 40/40 in the contralateral eyes, which indicates a significant interocular difference. BCVA values in the contralateral eyes were significantly correlated with patient age at surgery, but this result differed for BCVA in the operated eyes. The Pentacam analysis revealed no significant interocular differences in bilateral CTTL and ACV, but significant differences were found for ACD. CONCLUSIONS: At 3 months after surgery, unilateral pediatric cataract patients exhibited no significant interocular differences in identified anatomical parameters (except for ACD), and these parameters were not significantly correlated with BCVA in bilateral eyes. Therefore, amblyopia, but not anatomical factors, might be the main cause of interocular visual functional differences in our study population. TRIAL REGISTRATION: ClinicalTrial.gov, NCT02765230 , 05/05/2016, retrospectively registered.

Trichostatin A, a histone deacetylase inhibitor, suppresses proliferation and epithelial-mesenchymal transition in retinal pigment epithelium cells.

The proliferation and epithelial-mesenchymal transition (EMT) of retinal pigment epithelium (RPE) cells are the major pathological changes in development of proliferative vitreoretinopathy (PVR), which leads to severe visual impairment. Histone deacetylases (HDACs)-mediated epigenetic mechanisms play important roles in controlling various physiological and pathological events. However, whether HDACs are involved in the regulation of proliferation and EMT in PRE cells remains unidentified. In this study, we evaluated the expression profile of HDAC family (18 genes) and found that some of class I and class II HDACs were up-regulated in transforming growth factor-ß2 (TGF-ß2)/TGF-ß1-stimulated RPE cells. Tricostatin A (TSA), a class I and II HDAC inhibitor, suppressed the proliferation of RPE cells by G1 phase cell cycle arrest through inhibition of cyclin/CDK/p-Rb and induction of p21 and p27. In the meantime, TSA strongly prevented TGF-ß2-induced morphological changes and the up-regulation of α-SMA, collagen type I, collagen type IV, fibronectin, Snail and Slug. We also demonstrated that TSA affected not only the canonical Smad signalling pathway but also the non-canonical TGF-ß/Akt, MAPK and ERK1/2 pathways. Finally, we found that the underlying mechanism of TSA affects EMT in RPE cells also through down-regulating the Jagged/Notch signalling pathway. Therefore, this study may provide a new insight into the pathogenesis of PVR, and suggests that epigenetic treatment with HDAC inhibitors may have therapeutic value in the prevention and treatment of PVR.

Cucurbitacin IIa promotes the immunogenic cell death­inducing effect of doxorubicin and modulates immune microenvironment in liver cancer.

The immunogenic cell death (ICD) has aroused great interest in cancer immunotherapy. Doxorubicin (DOX), which can induce ICD, is a widely used chemotherapeutic drug in liver cancer. However, DOX­induced ICD is not potent enough to initiate a satisfactory immune response. Cucurbitacin IIa (CUIIa), a tetracyclic triterpene, is a biologically active compound present in the Cucurbitaceae family. The present study assessed the effects of the combination of DOX and CUIIa on the viability, colony formation, apoptosis and cell cycle of HepG2 cells. In vivo anticancer effect was performed in mice bearing H22 tumor xenografts. The hallmark expression of ICD was tested using immunofluorescence and an ATP assay kit. The immune microenvironment was analyzed using flow cytometry. The combination of CUIIa and DOX displayed potent apoptosis inducing, cell cycle arresting and in vivo anticancer effects, along with attenuated cardiotoxicity in H22 mice. The combination of DOX and CUIIa also facilitated ICD as manifested by elevated high­mobility group box 1, calreticulin and ATP secretion. This combination provoked a stronger immune response in H22 mice, including dendritic cell activation, increment of cytotoxic T cells and T helper 1 cells. Moreover, the proportion of immunosuppressive cells including myeloid­derived suppressor cells, T regulatory cells and M2­polarized macrophages, decreased. These data suggested that CUIIa is a promising combination partner with DOX for liver cancer treatment, probably via triggering ICD and remolding the immune microenvironment.

Four-Year Progression of Myopic Maculopathy in Children and Adolescents With High Myopia.

Importance: Individuals with high myopia younger than 18 years are at relatively high risk of progressively worsening myopic maculopathy. Additional studies are needed to investigate the progression of myopic maculopathy in this age group, as well as the risk factors associated with progression. Objective: To investigate the 4-year progression of myopic maculopathy in children and adolescents with high myopia, and to explore potential risk factors. Design, Setting, and Participants: This hospital-based observational study with 4-year follow-up included a total of 548 high myopic eyes (spherical power -6.00 or less diopters) of 274 participants aged 7 to 17 years. Participants underwent comprehensive ophthalmic examination at baseline and 4-year follow-up. Myopic maculopathy was accessed by the International Photographic Classification and Grading System. The data analysis was performed from August 1 to 15, 2023. Main Outcomes and Measures: The progression of myopic maculopathy progression over 4 years and associated risk factors. Results: The 4-year progression of myopic maculopathy was found in 67 of 548 eyes (12.2%) of 274 participants (138 girls [50.4%] at baseline and 4-year follow-up) with 88 lesion changes, including new signs of the tessellated fundus in 16 eyes (18.2%), diffuse atrophy in 12 eyes (13.6%), patchy atrophy in 2 eyes (2.3%), lacquer cracks in 9 eyes (10.2%), and enlargement of diffuse atrophy in 49 eyes (55.7%). By multivariable analysis, worse best-corrected visual acuity (odds ratio [OR], 6.68; 95% CI, 1.15-38.99; P = .04), longer axial length (AL) (OR, 1.73; 95% CI, 1.34-2.24; P < .001), faster AL elongation (OR, 302.83; 95% CI, 28.61-3205.64; P < .001), and more severe myopic maculopathy (diffuse atrophy; OR, 4.52; 95% CI, 1.98-10.30; P < .001 and patchy atrophy; OR, 3.82; 95% CI, 1.66-8.80; P = .002) were associated with myopic maculopathy progression. Conclusions and Relevance: In this observational study, the progression of myopic maculopathy was observed in approximately 12% of pediatric high myopes for 4 years. The major type of progression was the enlargement of diffuse atrophy. Risk factors for myopic maculopathy progression were worse best-corrected visual acuity, longer AL, faster AL elongation, and more severe myopic maculopathy. These findings support consideration of follow-up in these individuals and trying to identify those at higher risk for progression.

Interocular difference in crystalline lens morphology in children and adolescents with unilateral high myopia.

PURPOSE: To investigate the between-eye differences of the crystalline lens in subjects with unilateral high myopia and assess its contribution to the interocular refractive error disparity. METHODS: Children and adolescents with unilateral high myopia, defined as cycloplegic spherical equivalent (SE) ≤ -5D in one eye and ≥ -3D in the other eye, were recruited. Ocular biometric parameters, including axial length (AL) and lens thickness (LT), were measured by IOLMaster 700. Other lens-related parameters, including anterior lens radius of curvature (ALR) and posterior lens radius of curvature (PLR), were measured by CASIA2 swept-source optical coherence tomography. Lens power (LP) was calculated using Bennett's formula. Paired t-test was used to assess the between-eye difference in biometric parameters, and multiple regression analysis was used to assess factors associated with the between-eye SE difference. RESULTS: Ninety-one participants (6-18 years of age; 52.75% girls) were included. The highly myopic eyes showed significantly lower LP (P < 0.001) and smaller ALR (P < 0.001) than the contralateral eyes, while no significant difference was found in central LT. In both eyes, ALR was significantly related to SE (P = 0.001 and P = 0.006, respectively); while LT was not associated with SE (P = 0.051 and P = 0.052, respectively). Paired-eye analysis showed that the between-eye difference in ALR was the only lenticular parameter significantly associated with the between-eye difference in SE (P = 0.005). CONCLUSION: In highly myopic eyes, the crystalline lens reduced total power but morphologically changed to a more curved shape without significant lens thinning, suggesting that the LP loss is mainly achieved by reducing its internal power in high myopes.

Targeting glutamine metabolism improves sarcoma response to radiation therapy in vivo.

Diverse tumor metabolic phenotypes are influenced by the environment and genetic lesions. Whether these phenotypes extend to rhabdomyosarcoma (RMS) and how they might be leveraged to design new therapeutic approaches remains an open question. Thus, we utilized a Pax7Cre-ER-T2/+; NrasLSL-G12D/+; p53fl/fl (P7NP) murine model of sarcoma with mutations that most frequently occur in human embryonal RMS. To study metabolism, we infuse 13C-labeled glucose or glutamine into mice with sarcomas and show that sarcomas consume more glucose and glutamine than healthy muscle tissue. However, we reveal a marked shift from glucose consumption to glutamine metabolism after radiation therapy (RT). In addition, we show that inhibiting glutamine, either through genetic deletion of glutaminase (Gls1) or through pharmacological inhibition of glutaminase, leads to significant radiosensitization in vivo. This causes a significant increase in overall survival for mice with Gls1-deficient compared to Gls1-proficient sarcomas. Finally, Gls1-deficient sarcomas post-RT elevate levels of proteins involved in natural killer cell and interferon alpha/gamma responses, suggesting a possible role of innate immunity in the radiosensitization of Gls1-deficient sarcomas. Thus, our results indicate that glutamine contributes to radiation response in a mouse model of RMS.

Association Between Preoperative Ocular Parameters and Myopic Shift in Children Undergoing Primary Intraocular Lens Implantation.

Purpose: To evaluate the association between preoperative ocular parameters and myopic shift following primary intraocular lens (IOL) implantation in pediatric cataracts. Methods: Eyes from pediatric patients undergoing bilateral cataract surgery with primary IOL implantation were included. Eyes were grouped by age at surgery and subdivided into three axial length (AL) subgroups and three keratometry subgroups. Mixed-effects linear regression was utilized to assess the trend in myopic shift among subgroups. Multivariable analysis was performed to determine factors associated with myopic shift. Results: A total of 222 eyes were included. The median age at surgery was 4.36 years (interquartile range [IQR], 3.16-6.00 years) and the median follow-up was 4.18 years (IQR, 3.48-4.64 years). As preoperative AL increased, a decreased trend was observed in myopic shift and rate of myopic shift (P = 0.008 and P = 0.003, respectively, in the 4 to <6 years old group; P = 0.002 and P < 0.001, respectively, in the ≥6 years old group). Greater myopic shift and rate of myopic shift were associated with younger age at surgery (P = 0.008 and P = 0.008, respectively). Both myopic shift and rate of myopic shift were negatively associated with AL. Conclusions: Age at surgery and preoperative AL were associated with myopic shift in pediatric cataracts following primary IOL implantation. Adjusting the target refraction based on preoperative AL could potentially improve patients' long-term refractive outcome. Translational Relevance: This study may help to guide the selection of postoperative target refraction according to age at surgery and preoperative ocular parameters for pediatric cataracts.

Capsular Tension Ring Implantation for Intraocular Lens Decentration and Tilt in Highly Myopic Eyes: A Randomized Clinical Trial.

Importance: Capsular tension rings (CTRs) can support weak zonules and inhibit capsular shrinkage, thus potentially reducing intraocular lens (IOL) decentration and tilt. However, it has been debated whether CTRs can reduce IOL decentration and tilt in highly myopic eyes and whether CTR implantation is necessary for all highly myopic eyes. Objective: To evaluate the influence of CTR implantation on IOL decentration and tilt in highly myopic eyes. Design, Setting, and Participants: This randomized clinical trial was conducted between November 2021 and September 2023 at the Zhongshan Ophthalmic Center, Guangzhou, China. Patients with cataract and an axial length (AL) of 26 mm or longer were enrolled. Interventions: Participants were stratified into 3 groups based on the AL (stratum 1, 26 mm ≤ AL <28 mm; stratum 2, 28 mm ≤ AL <30mm; stratum 3, AL ≥30 mm), and further randomly assigned to the CTR group (a C-loop IOL combined with a CTR) or the control group (only a C-loop IOL) within each stratum. Main Outcomes and Measures: IOL decentration at 3 months after cataract surgery was evaluated using anterior segment optical coherence tomography. Results: A total of 186 eyes of 186 participants (mean [SD] age, 57.3 [10.9] years; 118 female [63.4%]) were randomized into the CTR group (93 [50%]) or control group (93 [50%]), with 87 eyes (93.6%) and 92 eyes (98.9%) completing follow-up at 3 months, respectively. The CTR group showed smaller IOL decentration (0.19 mm vs 0.23 mm; difference, -0.04 mm; 95% CI, -0.07 to -0.01 mm; P = .02) and tilt at 3 months, and lower proportions of clinically significant IOL decentration (≥0.4 mm) and tilt (≥7°) at 3 months compared with the control group. Similar results were only found in eyes with an AL of 30 mm or longer (IOL decentration: 0.20 mm vs 0.28 mm; difference, -0.08 mm; 95% CI, -0.14 to -0.02 mm; P = .01). Additionally, the CTR group showed a smaller change in IOL decentration from 1 week to 3 months, higher prediction accuracy, and better visual quality and patient satisfaction in this stratum. No differences were observed between the CTR and control groups in eyes with an AL less than 30 mm. Conclusions and Relevance: CTR implantation reduced C-loop IOL decentration and tilt, increased position stability, and improved visual quality in eyes with an AL of 30 mm or longer. These findings support use of CTR implantation in eyes with an AL of 30 mm or longer and implanted with C-loop IOLs. Trial Registration: ClinicalTrials.gov Identifier: NCT05161520.