To evaluate the efficacy and safety of OphTA, a preservative- and excipient-free formulation of triamcinolone acetonide for ophthalmic injection, in enhancing posterior vitreous cortex visualization during pars plana vitrectomy (PPV) among Chinese patients. This prospective, multicenter, open-label, single-arm Phase III trial utilized a pre-post treatment comparison design with masked independent central image review for the primary endpoint. Adults scheduled for PPV were enrolled. During surgery, OphTA (10 mg/mL) was injected intravitreally (0.5–4 mg total dose) after core vitrectomy until adequate visualization was achieved. Visualization grades (0 = none to 4 = excellent) were assessed pre- and post-instillation by both masked independent reviewers and operating surgeons. The primary endpoint was the change in grade assessed by independent reviewers, analyzed against a pre-defined clinically meaningful margin of 2 points using a one-sided Wilcoxon signed-rank test (α = 0.025). Safety assessments included adverse events (AEs) monitoring up to Day 7 ± 1 postoperatively. A total of 120 subjects were enrolled; 115 received OphTA (Safety Set [SS] and Full Analysis Set [FAS]), and 103 constituted the Per-Protocol Set (PPS). For the primary endpoint, the mean (SD) visualization grade in the FAS significantly improved from 1.6 (1.24) pre-instillation to 3.6 (0.71) post-instillation (mean increase: 2.0 points; P = 0.0244), the PPS analysis yielded consistent results (P = 0.0183), meeting the pre-specified criterion. Surgeon assessments (FAS, n = 115) corroborated these findings, showing a significant grade improvement from 0.6 (0.69) to 3.5 (0.54) (P < 0.0001), also meeting the pre-specified criterion. Post-hoc analysis showed a shift from 90.4

BACKGROUND:Dry eye disease (DED) commonly impairs quality of life. This phase 3, randomized, double-masked, multicenter, vehicle-controlled trial evaluated the efficacy of 5.0% lifitegrast ophthalmic solution (KH732) in improving signs and symptoms of DED. METHODS:Adults with moderate-to-severe DED and corneal staining score ≥2.0 in any corneal region were randomized 1:1 to lifitegrast (KH732) or vehicle twice daily for 84 days after a 3-7-day vehicle washout. The primary endpoint was change from baseline in inferior corneal staining score (ICSS) at Day 84. Secondary endpoints included changes in total corneal staining score, Eye Dryness Score (EDS), Ocular Surface Disease Index (OSDI), 7-item visual analogue scale, and Ocular Discomfort Score. RESULTS:At Day 84, lifitegrast (n = 309) significantly reduced ICSS versus vehicle (n = 306) (P = 0.027). In a post hoc analysis, the effect was more pronounced in participants with the highest baseline staining in the inferior region (P = 0.046). Lifitegrast also significantly improved EDS (adjusted P = 0.006), ocular discomfort (adjusted P = 0.010), photophobia (adjusted P = 0.004), and OSDI (adjusted P = 0.014) versus vehicle. Post hoc analyses showed significant between-group differences in EDS, photophobia, and OSDI as early as Day 14. No serious ocular adverse events were reported. CONCLUSIONS:Lifitegrast (KH732) improved both signs and symptoms of DED and was generally well tolerated, with potentially greater benefit in patients with prominent inferior corneal staining.

PURPOSE:As the prevalence of high myopia increases around the world, the incidence of highly myopic cataract (HMC) would increase and present clinicians with unique management challenges. This modified Delphi consensus study aimed to establish practical recommendations for HMC diagnosis and treatment, addressing key controversies in preoperative evaluation, surgical considerations, and postoperative care. METHODS:An international panel of 30 cataract experts from 14 countries/territories participated in this two-round e-Delphi study. Consensus was defined as ≥ 75% agreement on 5-point Likert-scale statements covering disease characterization, preoperative evaluation, intraoperative precautions, and postoperative care. RESULTS:A formal consensus was reached by a broad majority of the panel (86.67%) to endorse HMC as a separate disease category, typically manifesting 10-20 years earlier than age-related cataracts. Key consensus included: use of combined IOL formula calculations (96.67% agreement), preference for hydrophobic acrylic intraocular lens (96.67%), and mandatory 3-month postoperative retinal exams (96.67%). Controversies persisted regarding immediate sequential bilateral surgery, prophylactic routine implantation of a capsular tension ring, and postoperative steroid regime. CONCLUSIONS:We present commonly agreed recommendations for the clinical management of HMC, which include tailored surgical approaches and vigilant postoperative monitoring to address this growing public health challenge.

Purpose:To evaluate the associations of the triglyceride-glucose (TyG) index and TyG-derived metrics with diabetic retinopathy (DR) subtypes, retinal lesions, and retinal vascular metrics in adults with type 2 diabetes (T2D). Design:A population-based, prospective cohort study. Participants:One thousand nine hundred sixty adults with T2D, followed for a mean of 21.2 months. Methods:Outcomes included ETDRS-graded DR subtypes (advanced DR, vision-threatening DR [VTDR], diabetic macular edema [DME]); retinal lesions (hemorrhages/microaneurysms, hard exudates, soft exudates [SE]); and retinal vascular metrics (central retinal artery equivalent, central retinal vein equivalent, arteriole-to-venule ratio). Associations of TyG and TyG-derived indices with these outcomes were assessed using regression models with multivariable adjustments. Restricted cubic spline regression was applied to test for nonlinear associations. Mediation analyses by hemoglobin A1c (HbA1c) were conducted with bootstrap replications. Bonferroni correction was applied to control for type I error. Main Outcome Measures:Associations of TyG and TyG-derived indices with prevalent and incident DR subtypes, retinal lesions, and retinal vascular metrics. Results:At baseline, TyG and TyG-WHR (TyG × waist-to-hip ratio) were significantly associated (P ≤ 0.005) with advanced DR (odds ratio [OR] ≥ 2.12), VTDR (OR ≥ 1.77), and DME (OR ≥ 1.79). The TyG and TyG-WHtR (TyG × waist-to-height ratio) were also significantly linked to SE (OR ≥ 1.71, P ≤ 0.005), an early DR vascular abnormality. Longitudinally, TyG-WHtR predicted incident advanced DR (OR range: 1.7-18.8, P = 0.007). Mediation analysis showed HbA1c mediated these associations (P ≤ 0.001), suggesting both glycemic and nonglycemic mechanisms. Conclusions:The TyG and its derived indices (TyG-WHR, TyG-WHtR) are associated with the presence and progression of early and severe retinal vascular abnormalities in T2D. These markers may aid in identifying patients at high risk for VTDR. Financial Disclosures:The authors have no proprietary or commercial interest in any materials discussed in this article.

Background:Recently, deep learning has become a popular area of research, and has revolutionized the diagnosis and prediction of ocular diseases, especially fundus diseases. This study aimed to conduct a bibliometric analysis of deep learning in the field of ophthalmology to describe international research trends and examine the current research directions. Methods:This cross-sectional bibliometric analysis examined the development of research on deep learning in the field of ophthalmology and its sub-topics from 2015 to 2024. Visualization of similarities (VOS)-viewer was used to analyze and evaluate 3,055 articles. Data from the articles were collected on a specific date (September 11, 2024) and downloaded from the Web of Science Core Collection (WOSCC) in plain-text format. Results:A total of 3,055 relevant articles on the WOSCC published from 2015 to 2024 were included in this analysis. The first article on the application of deep learning to ophthalmology was published in 2015, and the number of articles on the subject has grown significantly since 2019. China was the most productive country (n=1,187), followed by the United States (n=673). Sun Yat-sen University was the institution with the most publications. Cheng and Bogunovic were the most frequently published authors. The following four different clusters were identified based on a co-occurrence cluster analysis of high-frequency keywords: (I) deep learning for the segmentation and feature extraction of ophthalmic images; (II) deep learning for the automatic detection and classification of ophthalmic images; (III) application of deep learning to ophthalmic imaging techniques; and (IV) deep learning for the diagnosis and management of ophthalmic diseases. Conclusions:The analysis of fundus images and the clinical application of deep learning techniques have emerged as prominent research areas in the field of ophthalmology. The substantial increase in publications and citations signifies the expanding impact and global collaboration in the application of deep learning research to ophthalmology. By identifying four distinct clusters representing sub-topics in deep learning ophthalmology research, this study contributes to the understanding of current trends and potential future advancements in the field.

This study investigated the association between omega-3 polyunsaturated fatty acids (PUFAs) and cataract risk by combining observational and genetic approaches. A cross-sectional analysis of the National Health and Nutrition Examination Survey (2003-2008) showed that higher omega-3 PUFA intake was inversely associated with cataract risk (fully adjusted OR = 0.74, 95 % CI: 0.57-0.97, P = 0.041). This protective effect was corroborated by Mendelian randomization analyses using large-scale genetic data (inverse variance weighted OR = 0.92, 95 % CI: 0.86-0.99, P = 0.044), with consistent results across sensitivity analyses. Summary-data-based Mendelian randomization further identified ten genes linking omega-3 PUFA metabolism to cataract through pathways related to lipid biosynthesis, oxidative stress, and inflammation. These findings provide convergent evidence that omega-3 PUFA intake may reduce cataract risk and highlight putative molecular mechanisms underlying this association.

In ophthalmology, the quality of fundus images is critical for accurate diagnosis, both in clinical practice and in artificial intelligence (AI)-assisted diagnostics. Despite the broad view provided by ultrawide-field (UWF) imaging, pseudocolor images may conceal critical lesions necessary for precise diagnosis. To address this, we introduce UWF-Net, a sophisticated image enhancement algorithm that takes disease characteristics into consideration. Using the Fudan University Ultra-wide-field Image (FDUWI) dataset, which includes 11 294 Optos pseudocolor and 2 415 Zeiss true-color UWF images, each of which is rigorously annotated, UWF-Net combines global style modeling with feature-level lesion enhancement. Pathological consistency loss is also applied to maintain fundus feature integrity, significantly improving image quality. Quantitative and qualitative evaluations demonstrated that UWF-Net outperforms existing methods such as contrast limited adaptive histogram equalization (CLAHE) and structure and illumination constrained generative adversarial network (StillGAN), delivering superior retinal image quality, higher quality scores, and preserved feature details after enhancement. In disease classification tasks, images enhanced by UWF-Net showed notable improvements when processed with existing classification systems over those enhanced by StillGAN, demonstrating a 4.62% increase in sensitivity (SEN) and a 3.97% increase in accuracy (ACC). In a multicenter clinical setting, UWF-Net-enhanced images were preferred by ophthalmologic technicians and doctors, and yielded a significant reduction in diagnostic time ((13.17 ± 8.40) s for UWF-Net enhanced images vs (19.54 ± 12.40) s for original images) and an increase in diagnostic accuracy (87.71% for UWF-Net enhanced images vs 80.40% for original images). Our research verifies that UWF-Net markedly improves the quality of UWF imaging, facilitating better clinical outcomes and more reliable AI-assisted disease classification. The clinical integration of UWF-Net holds great promise for enhancing diagnostic processes and patient care in ophthalmology.

INTRODUCTION:Diabetic cataract (DC) is a common ocular complication of diabetes. Mitofusin 2 (MFN2), a mitochondrial fusion protein, is involved in the pathogenesis of cataract and diabetic complications. However, its role and molecular mechanisms in DC remain unclear. MATERIALS AND METHODS:DC models in rats were induced by intraperitoneal injection of streptozocin (STZ) for 12 weeks. We measured the body weight of rats, blood glucose concentrations, sorbitol dehydrogenase (SDH) activity and advanced glycation end products (AGE) content in the lenses of rats. MFN2 mRNA and protein expression levels in the lenses were detected by RT-qPCR and western blot assays. In vitro, human lens epithelial (HLE) B3 cells were treated for 48 h with 25 mM glucose (high glucose, HG) to induce cell damage. To determine the role of MFN2 in HG-induced cell damage, HLE-B3 cells were transfected with lentivirus loaded with MFN2 overexpression plasmid or short hairpin RNA (shRNA) to overexpress or knock down MFN2 expression, followed by HG exposure. Cell viability was assessed by CCK-8 assay. Flow cytometry was used to detect cell apoptosis and reactive oxygen species (ROS) level. JC-1 staining showed the changes in mitochondrial membrane potential (Δψm). The mediators related to apoptosis, mitochondrial damage, and autophagy were determined. RESULTS:STZ-administrated rats showed reduced body weight, increased blood glucose levels, elevated SDH activity and AGE content, suggesting successful establishment of the DC rat model. Interestingly, MFN2 expression was significantly downregulated in DC rat lens and HG-induced HLE-B3 cells. Further analysis showed that under HG conditions, MFN2 overexpression enhanced cell viability and inhibited apoptosis accompanied by decreased Bax, cleaved caspase-9 and increased Bcl-2 expression in HLE-B3 cells. MFN2 overexpression also suppressed the mitochondrial damage elicited by HG as manifested by reduced ROS production, recovered Δψm and increased mitochondrial cytochrome c (Cyto c) level. Moreover, MFN2 overexpression increased LC3BⅡ/LC3BⅠ ratio and Beclin-1 expression, but decreased p62 level, and blocked the phosphorylation of mTOR in HG-treated HLE-B3 cells. In contrast, MFN2 silencing exerted opposite effects. CONCLUSIONS:Presented findings indicate that MFN2 expression may be essential for preventing lens epithelial cell apoptosis during development of diabetic cataract.

Purpose:The purpose of this study was to investigate the role of lncRNA H19 in epithelial-mesenchymal transition (EMT) and its molecular mechanism in fibrotic cataracts.Methods:TGF-β2-induced EMT was induced in human lens epithelial cell line (HLECs) and rat lens explants to mimic posterior capsular opacification (PCO) in vitro and in vivo. Anterior subcapsular cataract (ASC) was induced in C57BL/6J mice. The long noncoding RNA (lncRNA) H19 (H19) expression was detected by RT-qPCR. Whole-mount staining of lens anterior capsule was used to detect α-SMA and vimentin. Lentiviruses carrying shRNA or H19 vector were transfected in HLECs to knockdown or overexpress H19. Cell migration and proliferation were characterized by EdU, Transwell, and scratch assay. EMT level was detected by Western blotting and immunofluorescence. The rAAV2 carrying mouse H19 shRNA was injected into ASC model mouse anterior chambers as a gene therapy to determine its therapeutic potential.Results:PCO and ASC models were built successfully. We found H19 upregulation in PCO and ASC models in vivo and in vitro. Overexpression of H19 by lentivirus transfection increased cell migration, proliferation, and EMT. In addition, H19 knockdown by lentivirus suppressed cell migration, proliferation, and EMT levels in HLECs. Moreover, transfection of rAAV2 H19 shRNA alleviated fibrotic area in ASC mouse lens anterior capsules.Conclusions:Excessive H19 participates in lens fibrosis. Overexpression of H19 increases, whereas knockdown of H19 ameliorates HLECs migration, proliferation, and EMT. These results demonstrate H19 might be a potential target for fibrotic cataracts.

ObjectiveGlaucoma has currently become the second leading cause of blindness in the world. Serum vitamin B12 level has been found to be involved in the development and progression of glaucoma. We performed the present study to confirm this association.MethodsThis cross-sectional study included 594 participants aged 40 years and older in the National Health and Nutrition Examination Survey (NHANES) from 2005 to 2008. Retinal imaging was performed using the Ophthalmic Digital Imaging system (Retinography) to assess the retina for the presence of features of glaucomatous lesions. Logistic regression models were used to assess the association between dietary vitamin intake and glaucoma.ResultsAfter screening, 594 subjects were finally included. Among all vitamin intakes, we observed significant differences between the two groups for vitamin B12 intake (5.93 vs. 4.77 mg, p = 0.033). According to the logistic regression results, the intake of vitamin B12 was significantly positively associated with glaucoma (model 1: OR = 1.078, 95% CI = 1.019–1.141; model 2: OR = 1.092, 95% CI = 1.031–1.158; model 3: OR = 1.092, 95% CI = 1.029–1.158). After performing a quantile regression, we observed a significant positive association between vitamin B12 intake and incident glaucoma in the fourth quartile (model 1: OR = 1.133, 95% CI = 1.060–1.210; model 2: OR = 1.141, 95% CI = 1.072–1.215; model 3: OR = 1.146, 95% CI = 1.071–1.226).ConclusionsTherefore, the above results, high-dose intake of vitamin B12 may promote the development of glaucoma.

Oxidative stress-induced lens epithelial cells (LECs) death plays a pivotal role in age-related cataract (ARC) with severe visual impairment, in which ferroptosis is gradually receiving numerous attention resulting from lipid peroxide accumulation and reactive oxygen species (ROS) overproduction. However, the essential pathogenic factors and the targeted medical strategies still remain skeptical and indistinct. In this work, by transmission electron microscopy (TEM) analysis, the major pathological courses in the LECs of ARC patients have been identified as ferroptosis, which was manifested with remarkable mitochondrial alterations, and similar results were found in aged mice (24-month-old). Furthermore, the primary pathological processes in the NaIO3-induced mice and HLE-B3 cell model have also been verified to be ferroptosis with an irreplaceable function of Nrf2, proved by the increased sensitivity to ferroptosis when Nrf2 was blocked in Nrf2-KO mice and si-Nrf2-treated HLE-B3 cells. Importantly, it has been found that an increased expression of GSK-3β was indicated in low-Nrf2-expressed tissues and cells. Subsequently, the contributions of abnormal GSK-3β expression to NaIO3-induced mice and HLE-B3 cell model were further evaluated, inhibition of GSK-3β utilizing SB216763 significantly alleviated LECs ferroptosis with less iron accumulation and ROS generation, as well as reversed expression alterations of ferroptosis markers, including GPX4, SLC7A11, SLC40A1, FTH1 and TfR1, in vitro and in vivo. Collectively, our findings conclude that targeting GSK-3β/Nrf2 balance might be a promising therapeutic strategy to mitigate LECs ferroptosis and thus probably delay the pathogenesis and development of ARC.

One of the major pathological processes in cataracts has been identified as ferroptosis. However, studies on the iron metabolism mechanism in lens epithelial cells (LECs) and the methods of effectively alleviating ferroptosis in LECs are scarce. Along these lines, we found that in the ultraviolet radiation b (UVB) induced cataract model in vitro and in vivo, the ferritin of LECs is over-degraded by lysosomes, resulting in the occurrence of iron homeostasis disorder. Glycine can affect the ferritin degradation through the proton-coupled amino acid transporter (PAT1) on the lysosome membrane, further upregulating the content of nuclear factor erythrocyte 2 related factor 2 (Nrf2) to reduce the damage of LECs from two aspects of regulating iron homeostasis and alleviating oxidative stress. By co-staining, we further demonstrate that there is a more sensitive poly-(rC)-binding protein 2 (PCBP2) transportation of iron ions in LECs after UVB irradiation. Additionally, this study illustrated the increased expression of nuclear receptor coactivator 4 (NCOA4) in NRF2-KO mice, indicating that Nrf2 may affect ferritin degradation by decreasing the expression of NCOA4. Collectively, glycine can effectively regulate cellular iron homeostasis by synergistically affecting the lysosome-dependent ferritin degradation and PCBP2-mediated ferrous ion transportation, ultimately delaying the development of cataracts.

IntroductionCataract is one of the leading causes of blindness and visual impairment, about 16 million people around the world. Trace elements play an important role in a variety of the processes in human body. This study aimed to investigate the association between daily dietary intake of trace elements and age-related cataract incidence based on data from the National Health and Nutrition Examination Survey (NHANES) 2001–2008.MethodsIron, zinc, copper, and selenium were conducted in this study among subjects aged 50 years and older for African Americans and 55 and older in US adults. Multivariate logistic regression analysis was used in different models to investigate the association of trace elements intake and cataract.ResultsAfter screening, 7,525 subjects were ultimately included in this study. A significant negative association was found between selenium intake and cataract incidence in adjusted models using multivariate logistic regression analysis (model 1: OR = 0.998, 95% CI = 0.997–1.000; model 2: OR = 0.997, 95% CI = 0.995–1.000; and model 3: OR = 0.998, 95% CI = 0.995–1.000). After dividing selenium intake into quintiles, significant negative associations between selenium intake and cataract were observed in the first quintile of model 3, the fourth and fifth quintiles of all models. In subgroup analyses adjusted for age and sex, a significant negative association was observed only in women aged 65–74 years.DiscussionOur study points out that maintaining daily dietary selenium intake at higher levels is helpful for cataract prevention, and that increasing daily dietary selenium intake in American women aged 65–74 years may contribute to the prevention of age-related cataract. The intakes of iron, zinc, copper may not be associated with age-related cataract.

Introduction: The present study was conducted to determine the association of transforming growth factor-beta (TGF-β) gene polymorphism and myopia. Method: Four hundred twelve articles were identified, of which 11 articles with 5213 participants in 4 countries were included in the final analysis. Review Manager software (RevMan, version 5.4) was used for data analysis. Result: Odds ratio (OR) value of TGF-β1 rs1800469 is 1.33 (95% confidence interval [CI] = 1.15–1.54) in the allelic model; in the dominant model is 1.76 (95% CI = 1.16–2.67); in homozygous model is 5.98 (95% CI = 4.31–8.06). OR value of TGF-β1 rs4803455 is 0.62 (95% CI = 0.43–0.88) in recessive model. TGF-β2 is not associated with myopia. Relevant study on TGF-β3 is scarce. Conclusion: Our systematic review and meta-analysis found that TGF-β1 rs4803455 and rs1800469 were correlated with myopia.

Objective:To establish an in vitro capsular bag model and compare the inhibitory effects of different 360° square-edge intraocular lens (IOL) on lens epithelial cells (LECs) migration. Methods:In vitro capsular bag model with posterior capsule opacification (PCO) was established using Transwell compartment, cell climbing slices, human collagen type Ⅳ, and IOL.The models were divided into Plate-loop HydroSmart group, C-loop HydroSmart group, and C-compensation-loop Hydrophobic group according to the different square-edge IOL implanted.A blank control group was set using the Transwell compartment without IOL.The early PCO pathological manifestations in lens epithelial cell line SRA01/04 cultured in the Transwell compartment were observed with an inverted microscope.The cell morphology in different groups was observed by hematoxylin and eosin staining.The cell counting and cell migration inhibition rate of anterior capsule and posterior capsule were calculated by Transwell assay and cell-exclusion zone assay, respectively. Results:The early pathological characteristics of PCO, such as early Soemmering ring and small Elschnig pearl, could be found in cells in the in vitro capsular bag model after 48-hour culture.The migrating cells in model groups were fibrous.No changes mentioned above were found in blank control group.The number of migrating cells in the anterior capsule of Plate-loop HydroSmart group, C-loop HydroSmart group, C-compensation-loop Hydrophobic group was 18.80±5.53, 24.67±9.80, and 34.47±10.80, respectively, and the number of migrating cells in the optical area of the posterior capsule of the three groups was 56.43±9.00, 162.20±16.38, and 121.30±12.01, respectively.The cell migration inhibition rate in the anterior capsule of Plate-loop HydroSmart group, C-loop HydroSmart group, C-compensation-loop Hydrophobic group was (92.02±1.94)%, (89.76±3.10)%, (86.27±4.54)%, respectively, and the cell migration inhibition rate in optical area of the posterior capsule of the three groups was (91.60±3.65)%, (70.14±5.35)%, (78.43±3.48)%, respectively.The number of migrating cells in the anterior capsule was lower and the cell migration rate inhibition was higher in Plate-loop HydroSmart group than C-compensation-loop Hydrophobic group, with significant differences (both at P<0.05). The number of migrating cells in the optical area of the posterior capsule and the cell migration inhibition rate was greater than those of C-loop HydroSmart group and C-compensation-loop Hydrophobic group, showing statistically significant differences (all at P<0.001). Conclusions:The in vitro capsular bag model can be used in PCO research.Compared with C-loop HydroSmart IOL and C-compensation-loop Hydrophobic IOL, Plate-loop HydroSmart IOL can more effectively inhibit the migration of LECs to the optical area of the posterior capsule.

Purpose To compare the correlation between degree of lens opacity and the phacoemulsification energy parameter in patients with age-related cataract as determined by slit lamp, 25-MHz ultrasound biomicroscopy (UBM), and Scheimpflug imaging (Pentacam) and to evaluate the application of these three methods to measuring lens opacification. Methods This observational study was conducted in 319 patients (381 eyes) with different types of age-related cataract. The average age of patients was 67.3 ± 11.4 years. The degree of lens opacity acquired by slit lamp, 25-MHz UBM, and Pentacam was determined by the Lens Opacity Classification System III (LOCSIII), pixel units calculated by ImageJ, and lens density, respectively. We primarily analyzed and compared the correlation between lens opacity and the cumulative dissipated energy (CDE) values of phacoemulsification. Results Cortical, nuclear, and posterior subcapsular (PSC) cataracts were evaluated as follows: LOCSIII grades 3.31 ± 1.42, 3.29 ± 1.49, and 0.91 ± 0.83; pixel units 120.91 ± 22.8, 93.2 ± 15.9, and 99.7 ± 13.0; and lens density 51.8 ± 31.2, 21.2 ± 6.10, and 53.3 ± 35.3, respectively. The CDE values were 12.1 ± 12.4, 13.5 ± 9.11, and 3.93 ± 1.96. In cortical cataract, there was a linear correlation among LOCSIII, pixel units, and CDE value (r = 0.560, r = 0.832, and r = 0.582, respectively; both P < 0.05), but lens density had no correlation with other parameters. In nuclear cataract, there was a linear correlation among LOCSIII, lens density, and CDE value (r = 0.747, r = 0.865, and r = 0.906, respectively; both P < 0.05), but pixel units had no correlation with other parameters. In PSC, only pixel units and LOCSIII showed a correlation. Conclusions The various imaging methods offered different advantages in terms of determining lens opacity, a feature related to types of age-related cataracts. Choosing the most suitable imaging method to evaluate lens opacification based on the type of age-related cataract is important for accurately predicting the phacoemulsification parameters for cataract surgery. Translational Relevance Determining the appropriate phacoemulsification strategy depends on quantitative analysis of the degree of lens opacity to reduce intraoperative and postoperative complications and to obtain the optimal postoperative visual outcome.

Objective: To perform a bibliometric analysis in the field of ocular drug delivery research to characterize the current international trends and to present visual representations of the past and emerging trends on ocular drug delivery research over the past decade. Method: In this cross-sectional study, a bibliometric analysis of data retrieved and extracted from the Web of Science Core Collection (WoSCC) database was performed to analyze evolution and theme trends on ocular drug delivery research from January 1, 2001, to December 31, 2020. A total of 4334 articles on ocular drug delivery were evaluated for specific characteristics, such as publication year, journals, authors, institutions, countries/ regions, references, and keywords. Co-authorship analysis, co-occurrence analysis, co-citation analysis, and network visualization were constructed by VOSviewer. Some important subtopics identified by bibliometric characterization were further discussed and reviewed. Results: From 2001 to 2020, the annual global publications increased by 746.15%, from 52 to 440. International Journal of Pharmaceutics published the most manuscripts (250 publications) and produced the highest citations (9509 citations), followed by Investigative Ophthalmology & Visual Science (202 publications) and Journal of Ocular Pharmacology and Therapeutics (136 publications). The United States (1289 publications, 31,512 citations), the University of Florida (82 publications, 2986 citations), and Chauhan, Anuj (52 publications, 2354 citations) were the most productive and impactful institution, country, and author respectively. The co-occurrence cluster analysis of the top 100 keywords form five clusters: (1) micro/nano ocular drug delivery systems; (2) the treatment of inflammation and posterior diseases; (3) macroscopic ocular drug delivery systems/devices; (4) the characteristics of drug delivery systems; (5) and the ocular drug delivery for glaucoma treatment. Diabetic macular edema, anti-VEGF, ranibizumab, bevacizumab, micelles and latanoprost, were the latest high-frequency keywords, indicating the emerging frontiers of ocular drug delivery. Further discussions into the subtopics were provided to assist researchers to determine the range of research topics and plan research direction. Conclusions: Over the last two decades there has been a progressive increase in the number of publications and citations on research related to ocular drug delivery across many countries, institutions, and authors. The present study sheds light on current trends, global collaboration patterns, basic knowledge, research hotspots, and emerging frontiers of ocular drug delivery. Novel solutions for ocular drug delivery and the treatment of inflammation and posterior diseases were the major themes over the last 20 years.

Uncovering the functions of genes in a complex biological process is fundamental for systems biology. However, currently there is no simple and reliable experimental tool available to conduct loss-of-function experiments for multiple genes in every possible combination in a single experiment, which is vital for parsing the interactive role of multiple genes in a given phenotype. In this study, we develop miR-AB, a new microRNA-based shRNA (shRNAmir) backbone for simplified, cost-effective, and error-proof production of shRNAmirs. After verification of its potent RNAi efficiency in vitro and in vivo, miR-AB was integrated into a viral toolkit containing multiple eukaryotic promoters to enable its application in diverse cell types. We further engineer eight fluorescent proteins emitting wavelengths across the entire visible spectrum into this toolkit and use it to set up a multicolor-barcoded multiplex RNAi assay where multiple genes are strongly and reliably silenced both individually and combinatorially at a single-cell level.

Vision loss can occur when the cornea loses transparency or changes shape. The most effective treatment to restore vision is to use full or partial layers of donor cornea for corneal transplantation. However, there is a severe shortage of donor corneas worldwide, with more than 98.5% of patients with corneal blindness waiting for donor corneas. In addition, there exist some problems such as the possibility of infection, allotransplantation immunologic rejection, and other problems after corneal transplantation. Therefore, tissue-engineering corneas have been widely studied over the years as a viable alternative to donor corneas, with different materials and methods. And in nearly ten years, the research has had breakthrough progress. The ultimate goal of the research is to construct a full or partial tissue-engineering graft with good transparency, biocompatibility, and appropriate mechanical strength to repair, regenerate, or replace diseased corneas. This review discusses the research progress and existing problems about the most frequently studied natural biomaterials in recent years. These biomaterials include amniotic membrane, acellular cornea, collagen, and silk. In addition to the future research directions, other challenges related to the biomaterials discussed in this field are illustrated.

The retinal pigment epithelium cells (RPE) are sensitive to oxidative stimuli due to long-term exposure to various environmental stimuli. Thus, the oxidative injury of RPE cells caused by the imbalance of redox homeostasis is one of the main pathogenic factors of age-related macular degeneration (AMD). But the sophisticated mechanisms linking AMD to oxidative stress are not fully elucidated. Activation of Nrf2 signal pathway can protect RPE cells from oxidative damage. The present study investigated the regulating mechanism of miR-125b in Nrf2 cascade and evaluated its antioxidant capacity. The in vitro studies indicated that overexpression of miR-125b substantially inhibited Keap1 expression, enhanced Nrf2 expression and induced Nrf2 nuclear translocation. Importantly, functional studies demonstrated that forced expression of miR-125b could significantly elevate cell proliferation and superoxide dismutase (SOD) levels while reduce reactive oxygen species (ROS) overproduction and malondialdehyde (MDA) formation. Further studies showed that miR-125b had no effect when Nrf2 was silenced in ARPE-19 cells. Additionally, the results identified that Nrf2 silence induced ROS accumulation enhances HIF-1α protein expression, while miR-125b could offset this effect via promoting HIF-1α protein degradation. Subsequent in vivo studies demonstrated that sodium iodate induced outer retina thinner was reversed with exogenous supplementation of miR-125b, which was cancelled in Nrf2 knockout mice. In conclusion, this study illustrated that miR-125b can protect RPE from oxidative damage via targeting Nrf2/HIF-1α signal pathway and potentially may serve as a therapeutic agent of AMD.