International journal of ophthalmology最新文献

Aim: To investigate the potential causal associations between 41 inflammatory cytokines and myopia using a two-sample Mendelian randomization (MR) approach.

Methods: Publicly available genome-wide association study (GWAS) datasets were utilized for this two-sample MR analysis. Inflammatory cytokine-related GWAS data were extracted from The University of Bristol's Research Data Repository, and myopia-related GWAS data were obtained from the FinnGen project. Single nucleotide polymorphisms (SNPs) associated with inflammatory cytokines were systematically selected as instrumental variables (IVs) based on three rigorous criteria: relevance, independence, and exclusion of pleiotropy. Five MR methods were employed for causal inference: the inverse-variance weighted (IVW) method as the primary analysis, supplemented by MR-Egger regression, weighted median estimator, simple mode, and weighted mode approaches. Sensitivity analyses were performed to evaluate the robustness of the causal estimates.

Results: A total of 773 myopia-associated SNPs were identified. MR analysis revealed that higher levels of macrophage inflammatory protein 1-α (MIP-1α) were associated with a 17% reduced risk of myopia [odds ratio (OR)=0.83; 95% confidence interval (CI): 0.69-0.99; P<0.05]. In contrast, elevated levels of eotaxin (OR=1.26; 95%CI: 1.07-1.47; P<0.01), stromal cell-derived factor-1α (SDF-1α; OR=1.68; 95% CI: 1.08-2.62; P<0.05), and interleukin-2 receptor subunit alpha (IL-2Rα; OR=1.25; 95%CI: 1.01-1.53; P<0.05) were significantly associated with an increased risk of myopia. Sensitivity analyses confirmed the reliability of these results.

Conclusion: This study provides evidence supporting a causal relationship between specific inflammatory cytokines and myopia. MIP-1α may act as a protective factor against myopia, while eotaxin, SDF-1α, and IL-2Rα are potential risk factors for myopia. These findings emphasize the critical role of inflammatory pathways in the pathogenesis of myopia, offering novel insights for the development of preventive and therapeutic strategies for myopia.

Aim: To evaluate the predictive value of pan-immune-inflammation value (PIV) in the diagnosis of proliferative diabetic retinopathy (PDR) and its association with the stage of PDR.

Methods: This observational case-control study included participants who underwent routine complete blood count testing. Inflammation-related indices, including neutrophil-to-lymphocyte ratio, systemic immune-inflammation index (SII), and PIV, were derived and analyzed. Receiver operating characteristic curve (ROC) analysis was applied to assess the diagnostic performance of these indices in distinguishing patients with PDR, with sensitivity, specificity, area under ROC, and optimal threshold values calculated. In addition, binary logistic regression analysis was performed to evaluate the association between inflammatory indices and PDR stage.

Results: This study included 205 patients: 60 with diabetes without retinopathy (mean age: 61.81±10.76y), 80 with PDR (mean age: 61.63±10.03y) and 65 healthy controls (mean age: 59.52±5.88y). The PDR group had significantly higher white blood cell (WBC, P<0.001), monocyte (MONO, P=0.009) and neutrophil (NEU) counts (P<0.001). SII and PIV had the highest sensitivity and area under ROC for predicting patients with PDR (0.822, 0.846, respectively). The optimal cut-off values for discriminating patients with PDR were determined to be >527.12 and >299.08 for SII and PIV, respectively. The logistic regression analysis demonstrated that a decrease in lymphocyte (LYM) count and an increase in platelet count (PLT), glycated haemoglobin (HbA1c), SII, and PIV were all significantly associated with the development of high-risk PDR (all P<0.05). PIV was more stable than independent MONO, LYM, PLT and NEU levels in predicting both the diagnosis and stage of PDR. The optimal cut-off value for PIV to discriminate patients with high-risk PDR was found to be >345.87 area under ROC=0.871, with sensitivity of 0.827 and specificity of 0.812.

Conclusion: PIV is a reliable, valuable, and inexpensive blood index that can be used for early detection and staging of PDR. PIV may therefore be essential to be used for the follow-up of diabetic patients.

Aim: To investigate the effects of zingerone (ZO) on the retina in diabetic rats.

Methods: A total of 70 rats were randomly selected and divided into seven groups [diabetic group (Dm+; n=10), diabetic+metformin group (Dm+Met; n=10), diabetic+ZO25 group (Dm+ZO25; n=10), diabetic+ZO50 group (Dm+ZO50; n=10), diabetic+metformin group+ZO 50 Group (Dm+Met+ZO50; n=10)]. Diabetes was induced by streptozotocin (STZ), and metformin and two different doses of ZO were administered via gavage. Retinal tissues were evaluated by histopathological and immunohistochemical analyses.

Results: In diabetic rats, severe retinal inflammation, tissue necrosis, and increased tumor necrosis factor-α (TNF-α) expression were observed. ZO administration reduced these effects in a dose-dependent manner. Protective effects of metformin alone were limited, and no synergistic benefit was observed in ZO+Met groups. Administration of 50 mg/kg ZO to non-diabetic rats caused no retinal toxicity. Additionally, elevated 8-OHdG and c-Jun N-terminal kinase (JNK) expressions in diabetic retinopathy models were significantly reduced by ZO treatment.

Conclusion: ZO can markedly reduce the pathological effects of the retina in a diabetic rat model.

To explore the mechanisms underlying ocular infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), we conducted a comprehensive review of current literature, focusing on viral entry pathways, receptor expression in ocular tissues, and associated clinical manifestations. This review encompasses studies published within the last five years with a focus on original research and systematic reviews that provide molecular, histological, or clinical evidence. The findings show that SARS-CoV-2 can infect ocular tissues through multiple receptors beyond angiotensin-converting enzyme 2 (ACE2), including transmembrane serine protease 2 (TMPRSS2), CD147, alanyl aminopeptidase N (ANPEP), dipeptidyl peptidase 4 (DPP4), angiotensin II receptor type 2 (AGTR2), and polymeric immunoglobulin receptor (PIGR), which are expressed in retinal, conjunctival, corneal, limbal, and photoreceptor cells. The virus may also reach ocular structures via neurovascular invasion. Clinically, patients with coronavirus disease 2019 (COVID-19) may present with a broad spectrum of ophthalmic manifestations, including conjunctivitis, hyperreflective lesions in the inner retinal layers, flame-shaped hemorrhages, cotton-wool spots, retinal pallor, hard exudates, and various forms of maculopathy, such as paracentral acute middle maculopathy and acute macular neuroretinopathy (AMN). These signs reflect both direct viral damage and secondary effects of systemic inflammation and microvascular injury. Understanding the molecular and clinical spectrum of ocular involvement is essential for early diagnosis, appropriate ophthalmologic care, and the prevention of long-term visual sequelae in patients affected by COVID-19.

Aim: To investigate the causal effect of obesity on cataract risk and explores the potential mediating roles of metabolites using Mendelian randomization (MR).

Methods: Summary-level data from large-scale genome-wide association studies to examine the relationship between obesity and cataract were utilized. Obesity-related traits, including body mass index (BMI), waist-to-hip ratio (WHR), and waist circumference (WC). A two-sample MR approach was employed to assess the causal effect of obesity on cataract risk, while potential mediators were identified from suitable genome-wide association studies (GWAS) datasets. Additionally, a metabolic pathway analysis was conducted.

Results: An increase of 1 standard deviation (SD) in BMI, WHR, and WC was associated with a significantly higher risk of cataract (BMI: odds ratio (OR) 1.0017, 95% confidence interval (CI): 1.0001-1.0032, P=0.0320; WHR: OR 1.0029, 95%CI: 1.0006-1.0051, P=0.0129; WC: OR 1.0020, 95%CI: 1.0001-1.0038, P=0.0390]. These associations remained robust after adjusting for confounding factors in multivariable MR analysis. Furthermore, a two-step MR analysis identified eight potential metabolic mediators, with one mediator showing a significant causal role in the relationship between obesity and cataract.

Conclusion: This work highlights the importance of addressing obesity as a modifiable risk factor for cataracts, particularly through metabolic pathways.

Aim: To investigate the sex-specific correlation between systemic factors and retinal neurovascular alterations in individuals with type 1 diabetes mellitus (T1DM) who do not exhibit signs of diabetic retinopathy (DR).

Methods: A cohort participant without DR diagnosed with T1DM, underwent comprehensive ophthalmologic evaluation, optical coherence tomography angiography retinal structural and microvascular density analysis, and systemic parameter assessment. Multiple linear regression analysis was used to investigate the impact of systemic parameters on retinal alterations in distinct gender groups.

Results: A total of 182 individuals were included, consisting of 85 males (mean age 23.28±12.75y) and 97 females (mean age 22.98±13.68y). Males exhibited significantly greater thickness in both the internal retinal layer and the entire retina compared to females (P<0.01), whereas females had higher densities of deep retinal vessels and choroidal capillaries (P<0.05). Additionally, glycemic control was found to have a notable influence on retinal thickness in males (P<0.05), while insulin function had a more pronounced impact on retinal structure in females (P<0.01). Furthermore, a significant correlation was observed between thyroid function markers and retinal parameters in both male and female (P<0.05).

Conclusion: Sex differences in alterations in retinal structure and microcirculation are observed in individuals with T1DM prior to the development of clinical DR, with a noted association between these changes and systemic parameters.

Aim: To investigate the impact of depression-like behavior on ocular surface homeostasis in a mouse model, with a focus on dry eye-like alterations.

Methods: Male C57BL/6J mice (10-12 weeks old) were randomly assigned to control or restraint stress (RS) groups. The RS group underwent three intermittent 24-hour restraint sessions to induce depressive-like behavior. Behavioral testing, tear secretion measurement, and corneal Oregon Green Dextran (OGD) staining were performed. Postmortem analyses included histological evaluation of lacrimal glands, goblet cell quantification using periodic acid-Schiff staining, and assessment of key inflammatory and apoptotic markers: interleukin (IL)-17, matrix metalloproteinases (MMP)-3, MMP-9, IL-13, interferon (IFN)-γ, and cleaved caspase-3 and -8.

Results: Repeated RS induced depression-like behavior and significant ocular surface changes. RS-treated mice showed increased corneal OGD uptake and upregulation of gene/protein expression of IL-17, MMP-3, and MMP-9 (P<0.05). Goblet cell density and IL-13 protein expression were reduced, while IFN-γ protein expression was elevated (P<0.05). Cleaved caspase-3 and -8 levels were significantly increased in both cornea and conjunctiva. Tear volume and lacrimal gland size were unchanged; however, mild inflammatory infiltration was observed in lacrimal glands.

Conclusion: Repeated RS leads to ocular surface inflammation and dry eye-like pathology, including corneal barrier disruption, goblet cell loss, and epithelial apoptosis. These findings suggest that depression contributes to the pathogenesis of dry eye disease via immune-mediated mechanisms.

Aim: To assess the current research status and emerging trends of the choriocapillaris (CC) by bibliometric analysis.

Methods: Publications spanning from January 2013 to May 2023 were retrieved on June 27th, 2023, using the Web of Science Core Collection. Bibliometric and visualized analyses were performed employing the bibliometrix, CiteSpace and VOSviewer.

Results: A total of 1563 papers met the inclusion criteria, and a publication growth trend was observed. The United States was the leading country in the CC field. Retina and Investigative Ophthalmology & Visual Science stood out as highly impactful and prolific journals. Research topics in the CC field encompassed choroidal neovascularization, choroidal thickness, central serous chorioretinopathy, age-related macular degeneration, myopia, choroidal vascularity index, and diabetic retinopathy, based on the co-citation analysis. The keyword "high myopia" experienced a burst lasting until 2023.

Conclusion: In the past decade, research in the field of CC has flourished due to recent advancements in choroidal imaging; with focus shifting towards elucidating its role in various diseases. This will provide novel insights into managing chorioretinal diseases and vision-preserving interventions.

Aim: To evaluate the differences and consistency of vault measurements obtained by Scheimpflug tomography (Pentacam), anterior segment optical coherence tomography (AS-OCT, CASIA II), and ultrasound biomicroscopy (UBM) following implantable collamer lens (ICL) V4c implantation.

Methods: Vault measurements were acquired using three modalities: Pentacam, CASIA II AS-OCT, and UBM. Repeated-measures analysis of variance was used to compare the vault values obtained by the three devices. The correlation and consistency of measurements among the three instruments were assessed using the Pearson correlation coefficient, intraclass correlation coefficient (ICC), and Bland-Altman plots.

Results: This retrospective study enrolled 210 myopic eyes of 210 patients (158 women and 52 men) who underwent ICL implantation: 108 eyes had a myopic ICL V4c implanted, and 102 eyes had a toric ICL V4c implanted. The mean vault values measured by Pentacam, CASIA II, and UBM were 452.64±204.20 µm, 538.57±203.54 µm, and 560.95±227.54 µm, respectively, with statistically significant differences among the three groups (P<0.05). Pearson correlation analysis showed strong positive correlations between vault values measured by different instruments (all P<0.001). ICC results indicated good consistency among the three measurement modalities (all P<0.001). Stratified analysis revealed that when the vault value was ≤250 µm, the correlation and consistency of measurements across the three instruments were lower than those in the medium and high vault subgroups.

Conclusion: Vault values measured by Pentacam are lower than those obtained by CASIA II and UBM, with UBM yielding the highest mean vault values. Measurements from the three instruments are not interchangeable but can serve as mutual references due to their significant correlation and good overall consistency. Pentacam and CASIA II demonstrate the highest consistency in vault measurement. Notably, when the vault value is ≤250 µm, the consistency between Pentacam and the other two instruments decreases significantly.

Aim: To investigate whether vaccinia-related kinase 1 (VRK1) mediates transforming growth factor-beta2 (TGF-β2)-caused epithelial-mesenchymal transition (EMT) and inflammatory responses in retinal pigment epithelial (RPE) cells through regulating snail family transcriptional repressor 1 (SNAI1), and to validate its role in a proliferative vitreoretinopathy (PVR) mouse model.

Methods: Human RPE cell line ARPE-19 cells were treated with TGF-β2 to construct an EMT model. Western blot detected VRK1 level. The effects of VRK1 on SNAI1 expression and biological behavior of ARPE-19 cells were detected by immunofluorescence, ELISA, Transwell, and scratch assay, and the interaction between VRK1 and SNAI1 was confirmed through immunoprecipitation. A PVR mouse model was constructed, and the effects of VRK1 or/and SNAI1 on retinal damage were assessed by pathologic staining. Inflammatory factors and EMT-related proteins were assessed with ELISA and Western blot.

Results: VRK1 was upregulated in ARPE-19 cells after TGF-β2 treatment. Overexpression of VRK1 increased cell viability, promoted cell migration and EMT, and the levels of inflammatory factors. Silencing of VRK1 reversed the above indexes. There was a direct interaction between VRK1 and SNAI1, and overexpresssion SNAI1 weakened the impacts of silencing of VRK1. In PVR mice, silencing of VRK1 ameliorated retinal structural damage, decreased proinflammatory factor levels, and suppressed SNAI1 and mesenchymal marker expression. SNAI1 overexpression antagonized the protective effects of silencing VRK1 and exacerbated EMT and inflammatory responses.

Conclusion: VRK1 plays a key role in retinal structural and inflammatory damage in PVR mice by regulating SNAI1 and mediating TGF-β2-caused EMT and inflammatory responses in RPE cells.