Robot-assisted vitreoretinal surgery is a precision-oriented approach for technically demanding retinal procedures, but its structure and clinical maturity remain incompletely defined. We mapped the global development of this field using bibliometric and visualization methods. Records indexed in the Science Citation Index Expanded of the Web of Science Core Collection were retrieved on May 1, 2026. Bibliometrix in R, CiteSpace, and SCImago Graphica were used to analyze publication output, collaboration networks, citation patterns, journal distribution, and keyword evolution. The final dataset comprised 129 records published from 2008 to May 2026, including 110 original articles and 19 reviews. Full-text review identified 98 original articles with substantive empirical evaluations: 53 technical/simulation studies, 35 preclinical studies, and 10 human clinical studies. Publication output remained low before 2017 but increased thereafter. The United States and China contributed the largest numbers of publications, Johns Hopkins University was the most productive institution, and several authors showed similarly high outputs. Journal and reference analyses revealed an interdisciplinary clinical-engineering knowledge base spanning ophthalmology, medical robotics, imaging, motion control, and computer-assisted intervention. Keyword analyses showed increasing attention to subretinal injection, optical coherence tomography-guided intervention, artificial intelligence, and computer vision. The predominance of technical/simulation and preclinical evaluations suggests that publication growth has outpaced the accumulation of human clinical evidence. Robot-assisted vitreoretinal surgery is therefore better positioned as a selective precision platform for high-demand retinal interventions than as a universal replacement for manual surgery. Future research should prioritize multicenter validation, clinically relevant outcomes, workflow integration, training, and cost-effectiveness.
The rapidly rising global prevalence of childhood myopia has become a major public health concern, accompanied by a continuous annual increase in relevant academic publications. Against this backdrop, this study adopted bibliometric methods to analyze the research hotspots and evolutionary trends in this field. Publications related to myopia in children and adolescents were collected from the Science Citation Index Expanded of the Web of Science Core Collection database. A bibliometric and visualization analysis was performed using Microsoft Office Excel and VOSviewer to identify the most influential countries, papers, and authors and to construct the visualization map of citation, co-citation, and co-occurrence. After screening, 3413 papers met the inclusion criteria. China had the largest number of published papers, whereas the United States enjoyed the highest citations. Moreover, cooperation network analysis showed close cooperation among China, the United States, and Australia. The review "Myopia" in 2012 was the most-cited article. Among the 10 most-cited articles, outdoor time and the development of myopia in children were the topics with the highest frequency. As an expert in the field of epidemiology of myopia research, Saw SM contributed the most citations. The burst keywords were divided into 3 clusters through co-occurrence analysis: epidemiology, management, and mechanism of myopia in children and adolescents. This bibliometric analysis of myopia in children and adolescents helps researchers identify hotspots and research frontiers in the field and might provide a direction that future research should concentrate on.
Provide expert-informed guidance on the integration of aflibercept 8 mg into routine clinical care for patients with neovascular age-related macular degeneration (nAMD) and diabetic macular oedema (DMO), based on clinical trial and real-world evidence. Sixteen retina specialists ('experts') met during the Association for Research in Vision and Ophthalmology (ARVO) annual meeting in May 2025 to discuss the clinical use of aflibercept 8 mg. A post-meeting online platform was used to collect additional independent input. Agreement was captured using binary responses and categorised as: all agreed (100%), majority agreed ( ≥ 75%), most agreed (50-74%), or non-consensus ( ≤ 50%). All experts agreed that aflibercept 8 mg may be considered as a first-line treatment in treatment-naïve patients with nAMD and DMO, and switching to aflibercept 8 mg can be considered for previously treated patients. The majority of experts agreed that switching patients with well-controlled disease on shorter or intermediate dosing intervals may enable further interval extension while maintaining disease control, and switching patients with poorly controlled disease may optimise anatomical outcomes and improve stability. Most experts agreed that three initial monthly loading doses are appropriate in newly diagnosed patients. No consensus was reached on optimal dosing-decision strategies after switching in patients with poorly controlled disease, nor on the timing of initial interval modification during treatment initiation. These expert opinions, informed by available, emerging clinical evidence and real-world clinical experience, support aflibercept 8 mg as a first-line and switch option for nAMD and DMO, using personalised treatment approaches for both treatment-naïve and previously treated patients.
To present an up-to-date summary of the association between ocular shape and myopia. We systematically searched PubMed, Embase, Web of Science, the Cochrane Library, CNKI and Wanfang from June 2009 to September 2025 for cross-sectional and cohort studies examining the association between ocular shape and myopia (PROSPERO: CRD42024558271). The Newcastle-Ottawa Scale and the Agency for Healthcare Research and Quality were used to evaluate the quality of included studies. Thirty-four studies were included. Ocular growth appears relatively uniform in non-myopic eyes whereas myopic eyes tend to show non-uniform expansion. Greater myopia is associated with asymmetric changes in both anterior and posterior ocular shape. Highly myopic eyes frequently display spheroid shapes with equatorial pyriform contours and macular staphylomas, with more pronounced posterior deformities linked to a higher risk of myopic complications. Longitudinal evidence suggests that baseline ocular shape may be associated with subsequent ocular morphological changes and myopia progression. Ocular shape is closely associated with myopia and myopic retinopathy. Existing studies remain mostly observational and heterogeneous, with small sample sizes in some studies limiting causal inference and precluding meta-analysis. Future studies are needed to better understand the potential value of ocular shape in myopia control. CRD 42024558271.
Topical ocular treatments for diabetic macular oedema (DMO) have not previously been considered effective. We aimed to assess the efficacy and safety of topical OCS-01 (dexamethasone 1.5% ophthalmic suspension) in the treatment of DMO. This is a multicentre, double-blind, randomised, vehicle-controlled phase 2/3 trial. The objective of Stage 1 (reported herein, Stage 2 is ongoing) was to evaluate the efficacy and safety of a dosing regimen of OCS-01 to use in Stage 2, specifically to estimate the magnitude of the treatment effect on BCVA. Stage 1 was conducted at 27 ophthalmology clinics in the USA and four in Hungary. Patients aged 18-85 years with DMO involving the central macula (central subfield thickness (CST) ≥310 μm by SD-OCT), and ETDRS letter score 24-65 in the study eye were included in the study. Key exclusion criteria were macular oedema with causes other than DMO, decreased BCVA due to causes other than DMO, significant macular ischemia which would have prevented gain in BCVA, or other ocular disease that may have caused substantial reduction in BCVA. Patients were randomised, using an automated interactive response system to generate randomisation codes, stratified for baseline BCVA (<60 versus ≥60) and lens status (phakic or nonphakic), in blocks of 6 in a 2:1 ratio to receive topical ocular OCS-01 or matching vehicle. Treatment was given six times/day for 6 weeks (loading phase), followed by three times/day for 6 weeks (maintenance phase). Patients, investigators and the study team were masked to treatment assignment. Masking of treatment was maintained by using a vehicle that was identical to OCS-01 but did not contain dexamethasone, and OCS-01 and vehicle were supplied in identical packaging. The primary endpoint was change from baseline to Week 6 in ETDRS letter score in the Intent-to-Treat Set (all randomised patients). Safety analyses were based on the Safety Set (all patients who received ≥1 dose of study drug). The trial is registered with ClinicalTrials.gov, NCT05066997. Between Oct 5, 2021 and March 16, 2023, 100 patients (53 male, 47 female) received OCS-01 and 48 (26 male, 22 female) received vehicle; 85 and 39 patients, respectively, completed the study. LS mean (SE) change from baseline to Week 6 in BCVA ETDRS letter score was significantly greater with OCS-01 than Vehicle: 7.2 (0.85) letters versus 3.1 (1.26) letters (LS mean difference 4.1 (1.52) letters, 95% CI 1.1,7.0, p = 0.0070). Ocular adverse events (AEs) in the study eye occurred in 47/100 (47%) patients in the OCS-01 group and 22/48 (46%) Vehicle patients. Whilst acknowledging that no formal hypothesis was tested in Stage 1, topical OCS-01 was well tolerated, with no unexpected safety findings, and improved visual acuity in patients with DMO over the 12-week duration of Stage 1 of this study. Further data are required. The dosing regimen was found to be appropriate for use in Stage 2, which will provide longer-term data. Oculis Sàrl, Lausanne, Switzerland.
Preloaded Descemet membrane endothelial keratoplasty (plDMEK), in which eye-bank validated donor tissues are prepared, folded, and loaded into delivery devices prior to shipment, has emerged as a promising strategy to standardize and expand access to endothelial keratoplasty. Protocols developed with both endothelium-in (endo-in) and endothelium-out (endo-out) loading configurations have shown to improve surgical efficiency, reproducibility, and tissue utilization while lowering procedural barriers. We compiled current laboratory and clinical evidence on plDMEK and compared endo-in versus endo-out techniques to inform best practices. Following PRISMA guidelines, studies published between June, 2016, and August, 2025, were identified through PubMed, Scopus, Web of Science, and Google Scholar. Thirty-nine studies met inclusion criteria (19 clinical, 20 laboratory). Across 1420 clinical eyes, the overall sample size-weighted rebubbling rate was 25.5%; with rates of 30.4% for endo-in and 19.3% for endo-out grafts. Both configurations produced meaningful visual improvement from baseline (0.18 logMAR for endo-in, 0.12 logMAR for endo-out; p = 0.31) with endothelial cell loss (ECL) of 38% (endo-in) and 32% (endo-out) (p = 0.33) at 12 months. Laboratory studies showed a pooled ECL of 10.2% (9.4% endo-in, 11% endo-out; p = 0.4112) after storing in the delivery device for up to five days. Both approaches appear to be reliable, safe, and clinically acceptable methods for graft preparation and delivery. While endo-out technique shows a trend toward lower post operative rebubbling compared to endo-in, study heterogeneity underscores the need for standardized reporting, longer follow-up, and direct comparative trials to guide global clinical adoption.
To systematically evaluate the efficacy of orthokeratology combined with atropine versus orthokeratology alone in treating myopia in children. Randomized controlled trials (RCTs) comparing the efficacy of orthokeratology combined with atropine versus orthokeratology alone for pediatric myopia were retrieved from databases including CNKI, Wanfang, VIP, CBM, PubMed, Cochrane Library, Embase, and Web of Science from inception to April 2025. Data were analyzed using RevMan 5.2 software. A total of 18 randomized controlled trials involving 1,669 myopic children were included. The analysis showed that the intervention group had greater improvements in axial elongation (SMD = -0.66, 95% CI = -0.80 to -0.53, p < 0.001), tear film break-up time (SMD = 0.48, 95% CI = 0.33 to 0.63, p < 0.001), and corneal curvature (SMD = -2.47, 95% CI = -4.21 to -0.73, p = 0.005) compared to the control group. However, no statistically significant differences were found between the two groups in uncorrected visual acuity (SMD = 0.49, 95% CI = -0.27 to 1.24, p = 0.21) or tear film lipid layer thickness (SMD = -0.00, 95% CI = -1.09 to 1.09, p = 1.00). In addition, increased pupil diameter (SMD = 0.37, 95% CI = 0.09 to 0.64, p < 0.001) and reduced accommodative amplitude (SMD = -1.50, 95% CI = -2.58 to -0.43, p = 0.006) reflected the side effects associated with combined atropine treatment. Compared with orthokeratology alone, orthokeratology combined with atropine treatment reduces axial elongation, tear film break-up time, and corneal curvature in myopic children, but shows no significant advantage in uncorrected visual acuity or tear film lipid layer thickness, while incurring side effects of increased pupil diameter and reduced accommodative amplitude.
Uveitis encompasses a group of intraocular inflammatory disorders that notably contribute to global visual morbidity. Persistent challenges include early diagnosis, accurate subtype classification and individualized treatment. Recent advances in omics technologies, including genomics, epigenetics, transcriptomics, single‑cell omics, proteomics, metabolomics, lipidomics and microbiome profiling, have reshaped the current understanding of uveitis pathogenesis by uncovering disease‑associated genetic variants, dynamic transcriptional landscapes, inflammatory proteins, metabolic alterations, and microbe‑host interactions. Notably, single‑cell RNA sequencing offers unprecedented insights into retinal immune cell heterogeneity and functional states, while radiomics is emerging as a valuable platform for imaging biomarkers. The present review summarizes key findings from multi‑omics studies in uveitis, described the sample sources and analytical strategies employed, and highlighted the transformative potential of integrative omics in precision ophthalmology. Multi‑omics approaches hold promise for identifying novel biomarkers and therapeutic targets, refining disease classification, and enabling tailored interventions for patients with uveitis.
Portable visual-field testing devices have emerged as accessible approaches for detecting and monitoring manifest glaucomatous visual-field loss, particularly where standard automated perimetry is difficult to access. Their diagnostic accuracy and clinical reliability, however, remain uncertain due to heterogeneous study designs, variable thresholds, and inconsistent performance metrics. This systematic review and meta-analysis aimed to evaluate the diagnostic accuracy, test duration, and correlation of all portable VF devices compared with SAP, across multiple device categories and glaucoma severities. A comprehensive search of PubMed, Scopus, Web of Science, Cochrane Central, ClinicalTrials.gov, WHO ICTRP, and Google Scholar was conducted from inception through December 2025, without language restrictions. Eligible studies included diagnostic-accuracy or cohort designs comparing portable VF devices, including virtual-reality, tablet-based, web-based, or paper-based against SAP as the reference standard. Two reviewers independently extracted data and assessed quality using QUADAS-2. Pooled sensitivity, specificity, and diagnostic odds ratios (DOR) were calculated using bivariate random-effects models, with heterogeneity and publication bias evaluated via I², τ², and Deeks' funnel asymmetry tests. Secondary outcomes included test duration and correlation coefficients for mean deviation (MD), pattern standard deviation (PSD), and visual field index (VFI). From 639 screened records, 21 studies involving 2,254 participants (1,362 glaucoma, 892 controls) were included. Pooled sensitivity was 86% (95% CI, 80-90) and pooled specificity 88% (95% CI, 80-93), with an overall DOR of 28.6 (95% CI, 14.3-57.2). Substantial heterogeneity was observed across studies and device categories. Virtual-reality/head-mounted devices showed the highest diagnostic performance, whereas tablet-based devices demonstrated the lowest pooled specificity; however, sensitivity did not differ significantly between device categories, and specificity differences were not statistically significant. Test durations were significantly shorter for portable perimetry overall (SMD - 1.60; 95% CI, - 2.63 to - 0.57), with the largest reductions for tablet-based and paper-based devices, whereas VR/head-mounted systems showed no significant difference. Global index correlations were strong (r = 0.82; 95% CI, 0.75-0.88). In included validation studies, portable visual-field devices showed promising diagnostic performance relative to SAP for detecting manifest glaucomatous visual-field loss in validation-study settings, and most devices reduced testing time. However, because many studies used case-control designs, pooled accuracy estimates may be optimistic. Prospective, population-based studies in unselected cohorts are needed before these technologies are used as stand-alone diagnostic tools. These technologies represent potentially scalable tools requiring further validation for improving global glaucoma detection and ongoing disease management.
To evaluate visual and refractive outcomes of the Alcon Clareon® T2 toric IOL (1.00 D cylinder at the IOL plane, ~ 0.65 D at the corneal plane) versus the Clareon® non-toric IOL. Single ophthalmology clinic in Haugesund, Norway. This was an exploratory single site randomized, unmasked, prospective clinical trial. The study was registered with clinicaltrials.gov (NCT06717607, registered retrospectively on 12/5/2024). Patients presenting for routine cataract surgery in one or both eyes, where at least one eye qualified for implantation of the T2 lens, were enrolled. Qualifying eyes were randomized to a T2 lens or a non-toric lens. Subjects were evaluated monocularly before surgery and three months postoperative. Testing included uncorrected and corrected distance visual acuity (VA), the manifest refraction, low contrast VA (photopic and mesopic, with and without glare) and contrast sensitivity (photopic and mesopic). These latter two tests were conducted with the distance correction in place. Fifty eyes of 43 subjects were successfully enrolled from 6/2022 to 5/2024, including 30 eyes (25 subjects) randomized to the toric IOL and 20 eyes (18 subjects) to the non-toric IOL. Analysis included all enrolled eyes. Subjects were matched for age (p = 0.59), sex (p = 0.30), mean keratometry (p = 0.44), anterior corneal astigmatism (p = 0.97), axial length (p = 0.12) and anterior chamber depth (p = 0.40). Postoperatively, there was no statistically significant difference in the spherical equivalent refraction (p = 0.08). Residual refractive cylinder was statistically significantly lower in the T2 group (0.22 ± 0.22 D vs. 0.59 ± 0.28 D, p < 0.01). The T2 group also had statistically significantly better uncorrected logMAR distance VA than the non-toric group (0.00 ± 0.08 vs. 0.09 ± 0.13, p < 0.01). Low contrast VA was not statistically significantly different between the two lens types under any test condition (p = 0.49 or higher in all cases), nor were photopic or mesopic contrast sensitivity (p = 0.71 and p = 0.63, respectively). Use of the low cylinder power toric IOL provided significantly better UDVA, with no significant differences in distance-corrected contrast sensitivity or low contrast acuity. The achieved cylinder correction was consistent with expectations. https://clinicaltrials.gov/, identifier NCT06717607.
Aspartyl-tRNA synthetase 2 (DARS2), the mitochondrial enzyme responsible for aminoacylation of aspartyl-tRNA, is traditionally known for its effect on protein synthesis. Recently, DARS2 is reported to be implicated in tumorigenesis. However, its specific effect on breast cancer (BC) is poorly understood. The present work employed bioinformatics tools for analyzing DARS2 expression among BC patients and its association with clinicopathological characteristics and patient prognosis. We evaluated DARS2 expression within BC cells and tissues and assessed how DARS2 knockdown or PI3K pathway activation affected cell growth, migration, invasion, apoptosis, as well as cell cycle progression. Mechanistically, we analyzed how DARS2 regulated the PI3K/Akt/GSK-3β/β-catenin pathway. Additionally, a xenograft tumor model was constructed to validate our in vitro findings. According to our observations, DARS2 expression significantly increased in BC cells and tissues. Knockdown of DARS2 markedly suppressed cell growth, invasion, migration, and epithelial-mesenchymal transition (EMT), but enhanced their apoptosis. Mechanistic studies revealed that DARS2 knockdown suppressed the PI3K/Akt/GSK-3β/β-catenin pathway, whereas PI3K pathway activation with 740Y-P reversed the impacts of DARS2 knockdown. In vivo experimental results further verified that DARS2 suppression significantly suppressed tumor growth and metastasis through downregulating the PI3K/Akt/GSK-3β/β-catenin pathway. Collectively, these results indicate that DARS2 promotes the growth, migration, invasion, and EMT of BC cells by regulating the PI3K/Akt/GSK-3β/β-catenin signaling pathway.
Ketone bodies are key metabolic intermediates with both neuroprotective and pro-oxidative properties; however, their role in glaucoma remains unclear. This study aimed to investigate associations between circulating ketone bodies and the incidence of primary open-angle glaucoma (POAG), as well as related ocular parameters, in the UK Biobank. Combined cross-sectional analysis and prospective cohort study. A total of 456 499 participants were included in the cohort analysis; 104 225 were included in the baseline intraocular pressure (IOP) analysis, 41 495 in the baseline ganglion cell complex (GCC) thickness analysis, and 39 498 in the IOP-adjusted GCC thickness analysis. Circulating ketone bodies were quantified using nuclear magnetic resonance-based metabolomics. Cox proportional hazards models were used to estimate hazard ratios for POAG incidence. Linear regression models assessed associations with baseline IOP and GCC thickness. Restricted cubic spline models were applied to evaluate dose-response relationships, and subgroup analyses were conducted to explore potential effect modification. Incidence of POAG. During follow-up, 2330 participants developed POAG. Higher circulating ketone body levels were associated with an increased incidence of POAG after full adjustment (hazard ratio: 1.93, 95% confidence interval [CI]: 1.25-2.99, P = 0.003). Elevated ketone body levels were also associated with higher baseline IOP (β = 1.84, 95% CI: 1.57-2.10, P < 0.001) and thinner GCC both before (β = -1.62, 95% CI: -2.66 to -0.57, P = 0.002) and after IOP adjustment (β = -1.48, 95% CI: -2.53 to -0.42, P = 0.006), suggesting associations that are partially IOP-independent. Elevated circulating ketone body levels were associated with a higher incidence of POAG and related ocular phenotypes. Circulating ketone body levels may serve as a potential biomarker of systemic metabolic dysregulation associated with increased POAG susceptibility.Financial Disclosure(s)Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
The vertebrate retina contains specialised regions for high-acuity vision, exemplified by the human fovea and its zebrafish analogue, the high acuity zone (HAZ). Despite the widespread use of zebrafish to model retinal disease, a stage-resolved quantitative reference describing normal eye, photoreceptor layer (PRL) and lens growth has been lacking. Here we apply contrast-enhanced micro-computed tomography to construct the first three-dimensional micro-CT normative atlas of wild-type zebrafish eye development across five larval stages (3, 5, 7, 10 and 18 dpf), mapping circumferential PRL thickness, eye and lens morphology, and compartment growth rates. Regional PRL thickening within the temporo-ventral region of the expected HAZ emerged by 5 dpf and was sustained by a localised redistribution of growth, persisting and extending towards the optic nerve through 18 dpf. The PRL, lens and eye grew through four phases, alternating between disproportionate PRL expansion and coordinated growth, while the eye remodelled from a nasal-dominant to a temporo-ventral-dominant form. This regional specialization was protracted relative to gross ocular growth and could proceed independently of it, paralleling the extended postnatal maturation of the human fovea. This atlas provides a quantitative baseline for distinguishing disease-induced changes from normal variation, supporting zebrafish models of foveal hypoplasia and related disorders.
Kidney fibrosis is the pathologic hallmark of chronic kidney disease (CKD) and is driven by fibroblast-to-myofibroblast transformation (FMT), excessive extracellular matrix accumulation, and persistent activation of transforming growth factor-β (TGFβ) signaling. Although TGFβ is a central mediator of fibrosis, its pleiotropic physiological functions have limited the development of direct anti-fibrotic therapies, highlighting the need to identify context-specific regulators of this pathway. Matrix Gla Protein (MGP) is a vitamin K-dependent extracellular protein best known for inhibiting vascular calcification; however, its role in kidney fibrosis remains unknown. Here, we demonstrate that MGP expression is markedly upregulated in fibroblasts from fibrotic kidneys in mouse models of chronic kidney injury and in human CKD samples. Using inducible global and fibroblast-specific Mgp knockout mice, we show that Mgp deficiency attenuates renal fibrosis, suppresses fibroblast activation, and preserves kidney function following folic acid nephropathy and unilateral ureteral obstruction. Mechanistically, MGP promotes FMT and amplifies TGFβ receptor/Smad3 signaling, whereas genetic or molecular inhibition of MGP blunts TGFβ-driven fibroblast activation both in vivo and in vitro. We further identify phosphorylation and γ-carboxylation as essential post-translational modifications required for the profibrotic activity of MGP. In addition, MGP interacts with bone morphogenetic protein-2 (BMP-2), reduces BMP-2 protein abundance, and counteracts BMP-2-mediated suppression of TGFβ signaling, thereby enhancing profibrotic responses. Collectively, these findings identify MGP as a previously unrecognized regulator of TGFβ-dependent fibroblast activation and kidney fibrosis, supporting MGP as a potential fibroblast-associated target for future strategies aimed at limiting CKD progression.
Hypertensive retinopathy is a microvascular complication caused by systemic hypertension and can lead to severe visual impairment. At present, the molecular mechanisms of this disease remain incompletely understood, particularly the global expression profiles and regulatory networks of non-coding RNA (ncRNA). This study aims to comprehensively analyze the genome-wide differential expression profiles of messenger RNA (mRNA), microRNA (miRNA), long non-coding RNA (lncRNA), and circular RNA (circRNA) in retinal tissues from a spontaneously hypertensive rat (SHR) model of hypertensive retinopathy, and to observe transcriptomic changes after treatment with the calcium channel blocker lacidipine, thereby revealing their potential roles in disease pathogenesis and identifying possible therapeutic targets. SHRs were used as a model of hypertensive retinopathy, and normotensive Wistar-Kyoto (WKY) rats were used as controls. Rats were divided into 3 groups: A control group (WKY), a model group (SHR), and a treatment group (SHR+lacidipine). Rats in the treatment group received lacidipine by gavage at 0.5 mg/(kg·d) for 8 consecutive weeks. At the end of the experiment, retinal tissues were collected for histopathological examination by hematoxylin and eosin (HE) staining and for high-throughput sequencing. The lncRNA library was used to analyze mRNA, lncRNA, and circRNA expression profiles, and the small RNA (sRNA) library was used to analyze miRNA expression profiles. Differential expression analysis was performed using DESeq2. The screening criteria were |log2 fold change (FC)|≥1 and false discovery rate (FDR) significance criteria for mRNAs and lncRNAs, and |log2FC|≥1 and P<0.05 for miRNAs and circRNAs as exploratory candidates. Differentially expressed RNAs were subjected to Gene Ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Competing endogenous RNA (ceRNA) regulatory networks involving lncRNA/circRNA-miRNA-mRNA were constructed through target prediction and co‑expression analysis. Ten mRNAs whose expression changes were reversed after treatment were selected for validation by real-time reverse transcription polymerase chain reaction (real-time RT-PCR; n=6 per group). Comparisons among multiple groups were performed using one-way analysis of variance and post hoc multiple-comparison tests. 1) Verification of the animal model: Blood pressure was significantly higher in the model group than in the control group. The model group exhibited edema of the retinal nerve fiber layer, dilation of vascular lumens, and increased retinal thickness. Lacidipine treatment reduced blood pressure and alleviated these pathological changes. 2) Differential expression of mRNAs: Compared with the control group, 870 mRNAs were significantly downregulated and 1 018 mRNAs were significantly upregulated in the model group. Compared with the model group, 2 644 mRNAs were significantly downregulated and 186 mRNAs were significantly upregulated in the treatment group. GO analysis showed that upregulated mRNAs in the model group were enriched in immune-inflammatory processes, such as leukocyte activation, chemotaxis, defense response, and regulation of tumor necrosis factor (TNF) production, whereas downregulated mRNAs were enriched in G protein-coupled receptor (GPCR) signaling, glycoprotein synthesis, ion channel activity, and related processes. KEGG analysis revealed that upregulated mRNAs in the model group were enriched in interleukin-17 (IL-17), TNF, oxidative stress, and lipid inflammatory mediator metabolic pathways, whereas downregulated mRNAs were enriched in phosphatidylinositol 3-kinase (PI3K)-protein kinase B (AKT) signaling, vascular smooth muscle contraction, extracellular matrix (ECM)-receptor interaction, and related pathways. In the treatment group, the downregulated mRNAs were mainly enriched in pathways related to immune-inflammatory activation, such as mast cell degranulation and leukocyte degranulation. 3) Treatment-reversed mRNAs: A total of 67 genes that were upregulated in the model group and downregulated after treatment were identified; these genes were mainly enriched in endoplasmic reticulum stress-associated apoptotic signaling, mitophagy, ubiquitin ligase activity, and related processes. In addition, 54 genes that were downregulated in the model group and upregulated after treatment were identified; these genes were mainly enriched in amino acid transport, integrin complex, focal adhesion, glutamate transport activity, and related processes. Real-time RT-PCR validated the expression changes of Med22, Rmt1, Sytl3, Itgb7, and Slc1a3 which were decreased in the model group and increased after treatment, as well as Rnf183, Lrrc29, Lat2, Hist1h4m, and Dpm3, which were increased in the model group and decreased after treatment. These findings were consistent with the sequencing results. 4) Differential expression of miRNAs: Compared with the control group, 30 miRNAs were downregulated and 26 miRNAs were upregulated in the model group. Compared with the model group, 14 miRNAs were downregulated and 53 miRNAs were upregulated in the treatment group. Treatment-reversed miRNAs were identified: Rno-miR-1-3p, novel_miR_1203, and novel_miR_1417 were upregulated in the model group and downregulated after treatment, whereas novel_miR_107 and novel_miR_905 were downregulated in the model group and upregulated after treatment. Their target genes were enriched in regulation of retinal cone/rod cell differentiation, ECM remodeling, the Notch pathway, fatty acid synthesis, and related processes. 5) Differential expression of lncRNAs: Compared with the control group, 786 lncRNAs were downregulated and 764 lncRNAs were upregulated in the model group. Compared with the model group, 217 lncRNAs were downregulated and 230 lncRNAs were upregulated in the treatment group. A total of 55 lncRNAs that were upregulated in the model group and downregulated after treatment, and 76 lncRNAs that were downregulated in the model group and upregulated after treatment, were identified. Their target genes were enriched in immune regulation, wound healing, vascular remodeling, retinol metabolism related to rod-mediated scotopic vision, glutamatergic neuron differentiation, the forkhead box O (FoxO) pathway, retinoic acid-inducible gene I (RIG-I)-like receptor signaling, and related processes. 6) Differential expression of circRNAs: Compared with the control group, 45 circRNAs were downregulated and 47 circRNAs were upregulated in the model group. Compared with the model group, 25 circRNAs were downregulated and 22 circRNAs were upregulated in the treatment group. Eleven circRNAs that were downregulated in the model group and upregulated after treatment, and 10 circRNAs that were upregulated in the model group and downregulated after treatment, were identified. Their host genes were enriched in regulation of synaptic neural signaling, second messenger transmission, calcium signaling, and vascular endothelial growth factor (VEGF) signaling pathways. 7) Construction of ceRNA networks: Based on expression patterns and target prediction, multiple lncRNA/circRNA-miRNA-mRNA regulatory networks were constructed. For example, the networks composed of rno_circ_Rims2_10, rno-miR-1-3p, and related mRNAs, such as Mmp14 and Fasn, as well as the novel_miR_1417 related network, may be involved in retinal stress responses, inflammatory regulation, and neurovascular remodeling. This study is the first to integrate and analyze retinal transcriptomic profiles of mRNAs, miRNAs, lncRNAs, and circRNAs in an SHR model of hypertensive retinopathy, and it reveals RNA expression changes associated with lacidipine treatment. The results suggest that immune-inflammatory activation, neurovascular dysfunction, and ncRNA-mediated ceRNA regulatory networks may participate in the pathogenesis of hypertensive retinopathy. The identified differentially expressed molecules and predicted regulatory axes provide a candidate molecular basis for further mechanistic validation and screening of potential therapeutic targets. 目的: 高血压视网膜病变是全身性高血压引起的微血管并发症，可导致严重的视力损害。目前对该病的分子机制认识尚不全面，尤其是非编码RNA(non-coding RNA，ncRNA)在其中的整体表达谱及调控网络缺乏系统研究。本研究旨在全面分析自发性高血压大鼠(spontaneously hypertensive rat，SHR)高血压视网膜病变模型视网膜组织中信使RNA(messenger RNA，mRNA)、微RNA(microRNA，miRNA)、长链非编码RNA(long non-coding RNA，lncRNA)和环状RNA(circular RNA，circRNA)的全基因组差异表达谱，并观察钙通道阻滞剂拉西地平治疗后的转录组变化，以揭示其参与疾病发病机制的潜在作用，并识别可能的治疗靶点。方法: 采用SHR作为高血压视网膜病变模型，正常血压Wistar-Kyoto(WKY)大鼠作为对照组。将大鼠分为3组:对照组(WKY)、模型组(SHR)和治疗组(SHR+拉西地平)。治疗组给予拉西地平0.5 mg/(kg·d)灌胃，连续8周。实验结束时收集视网膜组织，分别进行苏木精-伊红(hematoxylin and eosin，HE)染色、病理组织学检查和高通量测序。lncRNA文库用于分析mRNA、lncRNA和circRNA表达谱，小RNA(small RNA，sRNA)文库用于分析miRNA表达谱。使用DESeq2进行差异表达分析，筛选标准:mRNA和lncRNA以|log2倍数变化(fold change，FC)|≥1且错误发现率(false discovery rate，FDR)<0.05;miRNA和circRNA以|log2FC|≥1且P<0.05为探索性候选。对差异表达RNA进行基因本体(Gene Ontology，GO)功能注释和京都基因和基因组数据库(Kyoto Encyclopedia of Genes and Genomes，KEGG)信号通路富集分析。通过靶标预测和共表达分析构建lncRNA/circRNA-miRNA-mRNA的竞争性内源RNA(competing endogenous RNA，ceRNA)调控网络。选取10个治疗后逆转的mRNA进行实时反转录聚合酶链反应(real-time reverse transcription polymerase chain reaction，real-time RT-PCR)验证(每组6只)。多组间比较采用单因素方差分析及事后多重比较检验。结果: 1)动物模型验证:模型组血压显著高于对照组，视网膜神经纤维层水肿、血管管腔扩张、视网膜厚度增加;拉西地平治疗后血压降低并减轻了上述病理改变。2)mRNA差异表达:与对照组相比，模型组有870个mRNA表达显著下调、1 018个mRNA表达显著上调;与模型组相比，治疗组有2 644个mRNA表达显著下调、186个mRNA表达显著上调。GO分析显示模型组上调mRNA富集于免疫炎症过程[如白细胞活化、趋化性、防御反应，肿瘤坏死因子(tumor necrosis factor，TNF)产生调节]，下调mRNA富集于G蛋白偶联受体(G protein-coupled receptor，GPCR)信号、糖蛋白合成、离子通道活性等。KEGG分析显示模型组上调mRNA富集于白细胞介素-17(interleukin-17，IL-17)、TNF、氧化应激及脂质炎症介质代谢通路;下调mRNA富集于磷脂酰肌醇3激酶(phosphatidylinositol 3-kinase，PI3K)-蛋白激酶B(protein kinase B，AKT)信号、血管平滑肌收缩、细胞外基质(extracellular matrix，ECM)-受体相互作用等通路。治疗组中下调的mRNA主要富集于免疫炎症激活相关通路(如肥大细胞脱颗粒、白细胞脱颗粒)。3)治疗逆转的mRNA:鉴定出67个在模型组上调、治疗后下调的基因(主要富集于内质网应激凋亡信号、线粒体自噬、泛素连接酶活性等)，以及54个在模型组下调、治疗后上调的基因(主要富集于氨基酸转运、整合素复合物、黏着斑、谷氨酸转运活性等)。Real-time RT-PCR验证了Med22、Rmt1、Sytl3、Itgb7、Slc1a3(模型组降低，治疗后升高)及Rnf183、Lrrc29、Lat2、Hist1h4m、Dpm3(模型组升高，治疗后降低)的表达变化，与测序结果一致。4)miRNA差异表达:与对照组相比，模型组有30个miRNA下调、26个miRNA上调;与模型组相比，治疗组有14个miRNA下调、53个miRNA上调。筛选出治疗逆转的miRNA:Rno-miR-1-3p、novel_miR_1203、novel_miR_1417在模型组上调、治疗后下调;novel_miR_107、novel_miR_905在模型组下调、治疗后上调。其靶基因富集于视网膜视锥/视杆细胞分化调节、ECM重塑、Notch通路及脂肪酸合成等。5)lncRNA差异表达:与对照组相比，模型组有786个lncRNA下调、764个上调;与模型组相比，治疗组有217个lncRNA下调、230个上调。筛选出55个模型组上调、治疗后下调的lncRNA和76个模型组下调、治疗后上调的lncRNA。其靶基因富集于免疫调节、伤口愈合、血管重塑、视黄醇代谢(视杆细胞暗视觉)、谷氨酸能神经元分化、叉头框蛋白O(forkhead box O，FoxO)通路、维A酸诱导基因I样受体信号等。6)circRNA差异表达:与对照组相比，模型组有45个circRNA下调、47个上调;与模型组相比，治疗组有25个circRNA下调、22个上调。筛选出11个模型下调/治疗后上调的circRNA和10个模型上调/治疗后下调的circRNA。其宿主基因富集于突触神经信号调节、第二信使传递、钙信号和血管内皮生长因子(vascular endothelial growth factor，VEGF)信号通路。7)ceRNA网络构建:基于表达模式和靶标预测，构建了多个lncRNA/circRNA-miRNA-mRNA调控网络。例如，rno_circ_Rims2_10与rno-miR-1-3p及相关mRNA(如Mmp14、Fasn)组成的网络，以及novel_miR_1417相关网络，可能参与视网膜应激反应、炎症调控和神经血管重塑。结论: 本研究在SHR高血压视网膜病变模型中整合分析了mRNA、miRNA、lncRNA和circRNA的视网膜转录组图谱，并揭示了拉西地平治疗相关的RNA表达变化。结果提示，免疫炎症激活、神经血管功能紊乱及ncRNA介导的ceRNA调控网络可能参与高血压视网膜病变的发病机制。鉴定出的差异表达分子及预测的调控轴为进一步的机制验证和潜在治疗靶点筛选提供了候选分子基础。.
Prenatal attachment plays an important role in shaping early parent-infant relationships and maternal psychological adaptation. However, the intellectual structure, collaborative patterns, research hotspots, and thematic evolution of prenatal attachment research have not been systematically characterized. This study aimed to provide a comprehensive scientometric overview of global prenatal attachment research. Publications related to prenatal attachment were retrieved from the Web of Science Core Collection from database inception to December 31, 2024. Only English-language articles and reviews were included. The Joinpoint Regression Program was used to objectively identify changes in annual publication trends, while CiteSpace 6.2.R6, VOSviewer 1.6.20, and Scimago Graphica were used to analyze collaboration networks, co-citation patterns, keyword co-occurrence, keyword clustering, and burst terms. A total of 470 publications from 58 countries/regions were included. Joinpoint regression identified 1 statistically supported change point in 2014 (95% confidence interval: 2012-2016). Annual publication output increased slowly from 1978 to 2014 and accelerated markedly from 2014 to 2024. The United Kingdom, the United States, and Australia occupied central positions in the international collaboration network, whereas publication output and citation impact were not always aligned across countries and institutions. Keyword and co-citation analyses revealed a shift from conceptualization and measurement development toward psychosocial risk factors, high-risk populations, paternal involvement, and technology-assisted approaches. This scientometric analysis delineates the developmental trajectory, collaborative landscape, intellectual base, and emerging themes of prenatal attachment research. The findings suggest that the field has expanded from early conceptualization and measurement validation toward broader topics involving psychosocial factors, high-risk populations, paternal involvement, and technology-related approaches. Future studies should strengthen cross-regional collaboration, adopt longitudinal and population-specific designs, and rigorously evaluate emerging interventions before drawing clinical conclusions.
Ankylosing spondylitis (AS) is a chronic inflammatory disease frequently associated with anterior uveitis. While ocular involvement is typically considered anterior, recent evidence suggests subclinical posterior microvascular alterations. This study aimed to evaluate retinal and choroidal changes in AS patients with and without anterior uveitis using optical coherence tomography angiography (OCTA). This cross-sectional study included 77 participants: 22 AS patients with anterior uveitis (43 eyes), 22 AS patients without ocular involvement (44 eyes), and 33 healthy controls (66 eyes). All subjects underwent a comprehensive ophthalmologic examination and OCTA imaging. Quantitative OCTA parameters, including superficial and deep capillary plexus (SCP, DCP) vessel densities, foveal avascular zone (FAZ) metrics, and choriocapillaris flow area, were analyzed. Both AS groups demonstrated significantly lower SCP vessel densities compared to controls (p<0.001), particularly in whole, parafoveal, and perifoveal regions. DCP vessel densities were markedly reduced in AS patients with anterior uveitis compared to both non-uveitis AS patients and controls (p<0.05). No significant differences were observed in FAZ area (p = 0.084), although FAZ perimeter was smaller in the uveitis group (p=0.045). Choriocapillaris and outer retinal flow areas also differed significantly among groups (p<0.01). AS patients, especially those with anterior uveitis, exhibit subclinical retinal and choroidal microvascular alterations detectable by OCTA. These findings suggest posterior segment involvement beyond clinically apparent anterior uveitis and indicate that OCTA may be a useful non-invasive tool for detecting microvascular alterations. Further longitudinal studies are warranted to assess the prognostic and therapeutic implications of these alterations.
To investigate the effectiveness of spectacle lenses with highly aspherical lenslets (HAL) and orthokeratology (ortho-k) for myopia control and the change in the interocular axial length (AL) difference in binocular anisomyopic children over 1-year in a real-world setting. Retrospective analysis of 74 bilateral anisomyopes (8-14 years; 39 HAL, 35 ortho-k). Axial elongation (AE) and interocular AL difference were compared in both groups; spherical equivalent refraction (SER), spherical refraction (SR), refractive astigmatism (RA) and corneal astigmatism (CA) were evaluated for the HAL group. AE in the more myopic eye (MME) of the HAL group was significantly greater than the ortho-k group (0.24 ± 0.17 vs. 0.15 ± 0.15 mm, p = 0.007). However, the opposite finding was observed in the less myopic eye (LME) (0.20 ± 0.14 vs. 0.29 ± 0.23 mm, p = 0.01). The interocular AL difference was reduced in the ortho-k group (0.69 ± 0.41 vs. 0.54 ± 0.32 mm, p = 0.007), whereas no significant change was found in the HAL group (p = 0.09). AE was associated with baseline SER (β = 0.08, p = 0.008) in the ortho-k group and age (β = -0.04, p = 0.001) in the HAL group. The MME in the HAL group showed larger changes in SER (-0.39 ± 0.31 vs. -0.27 ± 0.30 D) and CA (-0.21 ± 0.29 vs. -0.11 ± 0.25 D) than the LME (both p ≤ 0.03). The change in SER was positively associated with age and baseline SER (β = 0.08; β = 0.07, both p ≤ 0.02) in the HAL group. Ortho-k reduced AE, more so in the MME and reduced the interocular AL asymmetry. HAL slowed AE symmetrically, with greater control in older and less-myopic children.
In this study, we sought to characterize systems-level vitreous proteomic alterations associated with vitreoretinal lymphoma (VRL) and determine whether coordinated proteomic signatures associated with diffuse large B-cell lymphoma (DLBCL) biology are detectable within the intraocular microenvironment. A cross-sectional observational study. We included 11 immunocompetent patients diagnosed with VRL (DLBCL subtype) and 4 patients with a macular hole to serve as the noninflammatory controls. Undiluted vitreous samples from 11 eyes with VRL and 4 control eyes were analyzed using the SomaScan 7K aptamer‑based proteomic platform (SomaLogic), enabling quantification of 6981 proteins from limited-volume specimens. Differential expression analysis was performed using empirical Bayes linear modeling with false discovery rate (FDR) correction, followed by Gene Ontology, Reactome, and gene set enrichment analyses. Differentially expressed vitreous proteins and enriched biological pathways in VRL and control samples. Unbiased proteomic profiling revealed a distinct molecular signature in VRL vitreous samples, characterized by a coordinated enrichment of proteins associated with nuclear and chromatin-related pathways. A total of 2499 proteins met the predefined differential expression criteria (|log2-fold change| ≥ 0.5; adjusted P < 0.10), including 2440 upregulated and 59 downregulated proteins in VRL. Unsupervised analyses demonstrated a clear separation between the groups. Across complementary analyses, VRL showed enrichment of proteins associated with nuclear, chromatin-related, and epigenetic regulatory pathways, including deoxyribonucleic acid methylation, polycomb repressive complex-2‑mediated histone modification, histone deacetylation, and cell cycle-related transcriptional regulation. In parallel, pathways related to extracellular matrix organization, vesicle-associated components, and growth factor signaling were relatively reduced. Gene set enrichment analyses supported enrichment of nuclear regulatory pathway signatures (FDR <0.05). Vitreoretinal lymphoma was characterized by enrichment of proteins associated with nuclear and epigenetic regulatory pathways and the relative suppression of extracellular structural pathways, suggesting substantial intraocular microenvironmental remodeling. These findings demonstrate that high-dimensional vitreous proteomics can capture proteomic features associated with lymphoma-related pathways and provide a framework for molecular characterization and biomarker discovery in intraocular lymphoma. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
Research into biomarkers has transformed the identification and management of many diseases. Keratoconus (KC) is a multifactorial corneal ectasia, and due to limited understanding of disease pathophysiology, no biomarkers have been fully validated. microRNAs (miRNAs) are involved in regulating gene expression. Differentially expressed miRNAs have been reported in KC corneal tissue and as biomarkers for other ocular disorders. Salivary biomarkers mirror systemic processes and saliva contains substantial miRNAs. However, it is unknown if salivary miRNAs are differentially expressed in KC. Salivary miRNAs were collected from healthy (n=16) and KC subjects (n=50) and measured by qRT-PCR. Upregulated gene expression of miR-939-5p, miR-26a-5p, miR-25-3p, and miR-92a-3p; and downregulated expression of miR-320a was observed. Bioinformatic analysis using Ingenuity Pathway Analysis identified 248 experimental validated miRNA target genes and an enriched subset of 16 genes uniquely related to KC corneal functions. Gene ontology analysis demonstrated the over-representation of genes involved in protein kinase complex, protein phosphorylation, cellular senescence, apoptosis, and stress response. Our data detected previously unknown KC-dependent dysregulation of salivary miRNA expression. Future studies are warranted to determine the viability of these miRNAs as possible KC biomarkers, and to further establish their pathophysiological function.