Background:Bisphenol A (BPA) is a pervasive environmental contaminant associated with various systemic toxicities. However, its specific mechanistic involvement in dry eye disease (DED) pathogenesis is not defined. This study aimed to evaluate the toxicological mechanisms of BPA in DED pathogenesis and identify the key molecular mediators driving ocular surface injury. Methods:Toxicity profiles of BPA were predicted using the ProTox and ADMETlab platforms. Network toxicology and machine learning were used to explore pathogenic pathways and molecular mechanisms. Mendelian randomization (MR) analysis was performed to assess the causal effects of candidate targets on DED. Immune infiltration analysis and Gene Set Enrichment Analysis (GSEA) were used to characterize functional features and immune associations. Molecular docking and molecular dynamics (MD) simulations evaluated the spatial engagement and stability between BPA and the hub target. Finally, in vitro assays (CCK-8, LDH release, propidium iodide staining, ROS detection, qRT-PCR, and Western blot) using human corneal epithelial cells (HCECs) were conducted to validate the BPA-induced cytotoxicity and the molecular mechanisms. Results:Toxicity assessments predicted significant ocular irritant and corrosive properties for BPA. Machine learning algorithms identified CASP1 as the hub gene. MR analysis provided genetic evidence that elevated CASP1 expression causally increases DED risk (OR = 1.11, 95% CI: 1.06-1.16). Molecular docking demonstrated stable binding affinity (-5.1 kcal/mol) between BPA and the CASP1 protein. 100-ns molecular dynamics simulations confirmed its structural equilibrium and spontaneous thermodynamic stability with an MM-PBSA binding free energy of -12.19 kcal/mol. In vitro, BPA exposure decreased HCEC viability, compromised membrane integrity, and triggered significant intracellular ROS accumulation. BPA significantly upregulated the mRNA and protein expression of caspase-1, GSDMD, IL-1β, and IL-18. The application of a CASP1 inhibitor reversed these alterations and mitigated ROS accumulation. Conclusion:This study suggests that CASP1 is a central molecular component in DED. BPA promotes ocular surface injury by activating the CASP1/GSDMD-mediated pyroptotic axis and its associated inflammatory cascade. Inhibition of CASP1 effectively abrogates this process, suggesting potential avenues for clinical intervention.

Purpose: To investigate the mechanism of regulatory effect of astaxanthin (AST) on macrophage polarization both in vitro and in vivo dry eye models induced by hyperosmolarity. Methods: 1. In vitro: Raw264.7 cells were pretreated with AST or liposomal AST (AST-Lipo) followed by hyperosmotic stimulation. Control groups included an untreated hyperosmotic group and an isotonic control group. The mRNA expression of iNOS, Arg-1, TNF-α, MyD88, IL-1β, and HMGB1 was detected by qRT-PCR. Protein expression of NF-κB, phosphorylated NF-κB p65 (p-NF-κB p65), TNF-α, MyD88, IL-1β, and HMGB1 was detected by Western blot. 2. In vivo: BALB/c mice were randomly divided into isotonic control, hyperosmotic (DE) model, hyperosmotic + AST-Lipo, and hyperosmotic + AST groups. Corneal damage was assessed by fluorescein staining. The mRNA and protein expression levels of iNOS, Arg-1, NF-κB, p-NF-κB p65, TNF-α, MyD88, IL-1β, and HMGB1 in mouse corneas were detected by qRT-PCR and Western blot, respectively. Results: 1. In vitro: Compared to the hyperosmotic group, pretreatment with AST or AST-Lipo significantly decreased mRNA expression of iNOS, and significantly increased mRNA expression of Arg-1. NF-κB protein expression showed no significant change, while p-NF-κB p65 protein expression was significantly decreased. mRNA and protein expression of TNF-α, MyD88, IL-1β, and HMGB1 were significantly reduced. The effects of AST-Lipo were more pronounced than those of AST alone. 2. In vivo: Compared to the DE model group, both AST and AST-Lipo treatment groups showed significantly reduced corneal fluorescein staining scores. mRNA expression of iNOS was significantly decreased, while Arg-1 mRNA expression was significantly increased. NF-κB protein expression was unchanged, but p-NF-κB p65 protein expression was significantly decreased. mRNA and protein expression of TNF-α, MyD88, IL-1β, and HMGB1 were significantly lower. Again, AST-Lipo showed stronger effects than AST. Conclusion: Astaxanthin can inhibit M1 macrophage polarization and promote M2 polarization by suppressing the HMGB1/MyD88/NF-κB signaling pathway, thereby exerting anti-inflammatory effects in hyperosmolarity-induced dry eye models in vitro and in vivo. Liposomal encapsulation enhances the bioavailability and efficacy of AST.

Objective: To investigate the vascular characteristic changes in the macular retina and choriocapillaris, as well as the choroidal vascularization of eyes with different degrees of myopia in juveniles using Swept-source Optical Coherence Tomography (SS-OCT), aiming to understand the pathophysiological characteristics of myopic eyes further. Methods: We conducted a retrospective case-control study involving 103 patients (198 eyes) aged 6–17 years who had undergone SS-OCT examination. Based on equivalent spherical power, they were divided into four groups: emmetropia group, low myopia group, moderate myopia group, and high myopia group. The density of superficial capillary plexuses (SCP), choriocapillaris (CC), choroid vessel (CV)layers, and subfoveal choroidal thickness (SFCT) in the macular area were measured using SS-OCT. Multivariate regression analysis was employed to determine the ocular and demographic factors associated with retinal and choroidal blood flow indicators. Results: In the temporal parafoveal area, the superficial capillary plexus (SCP) density was significantly lower in the moderate myopia group compared to the low myopia group (47.27 ± 2.21 vs. 48.51 ± 1.8, p = 0.002). Conversely, subfoveal choroidal vessel (CV) density was substantially higher in highly myopic eyes than in emmetropic eyes (56.98± 3.65 vs. 53.70 ± 4.31, p = 0.023). The multiple linear regression analysis showed that in the area under the fovea, thinner choroidal thickness is associated with higher choroidal vessel density. Specifically, as choroidal thickness decreases, the density of choroidal vessels increases (p = 0.024). Conclusions: For juveniles, with the progression of myopia, the density of retinal superficial blood vessels and choroidal capillaries remains at a relatively stable level, while the choroidal vessel density under the fovea gradually increases. The main cause of changes in choroidal vessel density is the thickness of choroid under the fovea.

Human cytomegalovirus (HCMV) has evolved sophisticated strategies to evade host immune defenses, enabling its persistent survival in human populations. HCMV intermediate-early protein 2 (IE2) has been identified as a crucial factor in immune evasion mechanisms. However, the specific immunomodulatory effects of IE2 on antigen presentation remain insufficiently explored. In this study, we established a transgenic mouse model to systematically examine the impact and molecular mechanisms of IE2 on macrophages (Mφs) antigen presentation in vivo. Our findings demonstrated that IE2 modifies Mφs' function by preventing their phagocytic activity and polarization. Additionally, IE2 inhibits Mφs overactivation both in vivo and in vitro, which raises IL-10 levels and activates the downstream mediator STAT3, which in turn decreases T cell immune responses by encouraging T helper 2 (Th2) type responses. In conclusion, these findings underscore the potential of IE2 as a critical regulator of immune evasion and may contribute to the development of novel, targeted therapeutic strategies against the virus.

INTRODUCTION:This was an in vivo animal study designed to investigate the interaction between dexamethasone (Dex) and microRNA-204 (miR-204) in a mouse alkali burn-induced corneal neovascularization (CNV) model. The function of miR-204 was then investigated in human mammary epithelial cells (HMECs) in vitro. MATERIALS AND METHODS:The CNV model was induced by corneal alkali burn in BLAB/c mice. The mice were randomly divided into five groups: normal control (Ctrl), alkali burn-induced corneal injury (Alkali), alkali burn + Dex (Dex), alkali burn + negative control (NTC), and alkali burn + miR-204 agomir (miR-204). Subconjunctival injection of NTC, Dex, or miR-204 agomir was conducted at 0, 3, and 6 days, respectively, after alkali burn. The corneas were collected at day 7 after injury, and the CNV area was observed using immunofluorescence staining. The expression of miR-204 was analyzed with quantitative real time (qRT)-PCR. In HMECs, exogenous miR-204 agomir or antagomir was used to strengthen or inhibit the expression of miR-204. Migration assays and tube formation studies were conducted to evaluate the function of miR-204 on HMECs. RESULTS:At 7 days post-alkali burn, CNV grew aggressively into the cornea. MicroRNA-204 expression was reduced in the Alkali group in contrast with the Ctrl group (P = .003). However, miR-204 was upregulated in the Dex group (vs. alkali group, P = .008). The CNV areas in the NTC and miR-204 groups were 59.30 ± 8.32% and 25.60 ± 2.30%, respectively (P = .002). In vitro, miR-204 agomir showed obvious inhibition on HMEC migration in contrast with NTC (P = .033) and miR-204 antagomir (P = .017). Compared with NTC, miR-204 agomir attenuated tube formation, while miR-204 antagomir accelerated HMEC tube formation (P < .05). CONCLUSION:The role of Dex in attenuating CNV may be partly attributed to miR-204. MiR-204 may be a potential therapeutic target in alkali burn-induced CNV.

PURPOSE:To explore the influence of preoperative factors, including varying pupil sizes and refractive attributes, on postoperative glare disability in patients undergoing implantable collamer lens (ICL) implantation. SETTING:Second Affiliated Hospital, Nanchang University, Nanchang, Jiangxi, China. DESIGN:Prospective observational study. METHODS:The preoperative ocular characteristics and 6-month postoperative glare status in eligible patients who underwent EVO-Visian ICL V4c (VICMO) implantation were analyzed. The glare disability criteria encompassed a glare symptom score >6 and glare sensitivity exceeding 1:2.7. Logistic regression analysis was used to explore the relationship between the preoperative ocular parameters and post-ICL glare. RESULTS:The study included 95 patients (mean age, 26.04 ± 6.29 years), comprising 30 men (58 eyes) and 65 women (129 eyes). Multivariate analysis revealed a significant correlation between postoperative glare disability and increased spherical power in preoperative mesopic pupils (β = -0.124, P = .039), as well as elevated cylinder power in preoperative mesopic (β = -0.412, P = .009) and photopic pupils (β = -0.430, P = .007). Moreover, a larger preoperative mesopic pupil diameter (β = 0.561, P = .005) demonstrated a significant correlation with glare disability. CONCLUSIONS:Preoperative mesopic pupil dimensions and associated refractive parameters, such as sphere and cylinder, were correlated with glare disability, including the cylinder aspect in photopic pupils, which can assist clinicians in optimizing preoperative selection for ICL implantation, aiding in the anticipation of potential glare disability risks.

Dry eye disease (DED) is a common eye disease in clinical practice. The crucial pathogenesis of DED is that hyperosmolarity activates oxidative stress signaling pathways in corneal epithelial and immune cells and, thus, produces inflammatory molecules. The complex pathological changes in the dry eye still need to be elucidated to facilitate treatment. In this study, we found that astaxanthin (AST) can protect against DED through the SLC7A11/GPX4 pathway. After treatment with AST, the SLC7A11/GPX4 pathway was positively activated in DED both in vivo and in vitro, accompanied by enhanced autophagy and decreased ferroptosis. In hyperosmolarity-induced DED corneal epithelial cells, AST increased the expression of ferritin to promote iron storage and reduce Fe2+ overload. It increased glutathione (GSH) and GPX4, scavenged reactive oxygen species (ROS) and lipid peroxide, and rescued the mitochondrial structure to prevent ferroptosis. Furthermore, inhibition of ferroptosis by ferrostatin-1 (Fer-1), iron chelator deferoxamine mesylate (DFO), or AST could activate healthy autophagic flux. In addition, in a dry eye mouse model, AST upregulated SLC7A11 and GPX4 and inhibited ferroptosis. To summarize, we found that AST can ameliorate DED by reinforcing the SLC7A11/GPX4 pathway, which mainly affects oxidative stress, autophagy, and ferroptosis processes.

AIMS:This study aimed to synthesize the variations in subfoveal choroidal thickness (SFCT) observed at different follow-up intervals in myopic children undergoing orthokeratology treatment. MATERIALS AND METHODS:Relevant articles were systematically retrieved from databases such as PubMed, EMBASE, Web of Science, and Cochrane Library. The retrieval period extended from the inception of these databases to November 2023. Means and standard deviations (SD) of baseline and post-treatment SFCT were selected as the results for analysis and calculation. RESULTS:A total of eight articles involving 478 eyes fulfilled the inclusion criteria. At 1 month, 3 months, and 6 months intervals, the SFCT demonstrated significant increases by 16.74 μm (95% CI: 8.66, 24.82; p < 0.0001), 13.41 μm (95% CI: 4.36, 22.45; p = 0.004), and 17.57 μm (95% CI: 8.41, 26.73; p = 0.0002), respectively. Besides, children treated with orthokeratology exhibited a notably thicker change of SFCT in comparison with children with single-vision spectacles (SVL) (WMD = 13.50, 95% CI: 11.69, 15.13; p < 0.0001). CONCLUSION:Myopic children undergoing orthokeratology treatment experience a discernible increase in SFCT at 1 month, 3 months, and 6 months. Furthermore, compared to children utilizing SVL, those undergoing orthokeratology manifest a more pronounced thickening of SFCT.

PurposeDry eye disease (DED) has a complex etiology and the roles of long noncoding RNAs (lncRNAs) in its pathophysiology are not completely understood. Autophagy is a self-eating process important for cell survival and homeostasis. The present study explored the role of myocardial infarction-associated transcript neighbor (MIATNB) long non-coding RNA in hyperosmolarity-induced autophagy and apoptosis in human corneal epithelial cell (HCEC)-based model of dry eye disease.MethodsIn vitro assays were performed with a human SV40 immortalized corneal epithelial cell line. Different concentrations of NaCl were used to create hyperosmolarity. HCECs were cultured in presence of 70-120 mM NaCl for 24 h to create an in vitro model of dry eye. RT-qPCR was performed to assess the expression of dry eye related LC3B, ATG16L, BECN1, ATG1, ATG7, ATG13, ATG5, ATG10, and ATG101 mRNAs and western blot analysis of LC3B and P62 and RFP -GFP-tagged LC3. Flow cytometry and western blot analysis of caspase 3, BCL2 and BAX were performed to detect apoptosis. Chloroquine (CQ) was used to inhibit autophagy pharmacologically.ResultsAutophagy flux was activated in HCECs subjected to hyperosmotic stress. Hyperosmolarity activated apoptosis and inhibited HCEC migration and autophagy. Hyperosmolarity upregulated MIATNB expression, while MIATNB knockdown inhibited autophagosome degradation and promoted HCEC apoptosis. Under hyperosmolar conditions, MIATNB knockdown also inhibited the degradation of autophagolysosomes and stimulated HCEC apoptosis.ConclusionMIATNB plays a vital role in dry eye pathogenesis and serves as a bridge between autophagy and apoptosis. Targeting MIATNB for DED treatment should be further evaluated.

To observe corneal nerve fibers and densitometry after small incision lenticule extraction (SMILE), femtosecond laser-assisted laser in situ keratomileusis (FS-LASIK) and laser-assisted subepithelial keratomileusis (LASEK) for high myopia. This is a prospective, cross-sectional research study. Patients with high myopia (equivalent spherical lens: −6.00 and −11.00D) who underwent laser corneal refractive surgery were divided into three groups: SMILE, FS-LASIK and LASEK. Scheimpflug imaging of corneal nerves in five areas was observed by confocal microscopy before and 6, 12 months after surgery. Corneal densitometry was measured by Pentacam anterior segment analysis system. Overall, 59 patients were enrolled. The nerve density in the central area did not recover to the preoperative level in three groups until 12 months. The density and length of corneal nerves in central and lower area were better in the SMILE group 6 months postoperatively (p = 0.01), while nerve density did not differ significantly among three groups 12 months postoperatively (p = 0.18). Nerve fibers in central and temporal region were wider in LASEK than that in other two groups at 6- and 12-month follow-up. Corneal densitometry in the central 6 mm diameter was significantly higher in the LASEK group compared with other two groups 6 months postoperatively (p = 0.04). Twelve months postoperatively, corneal densitometry in range of all zone was lower in SMILE than in FS-LASIK and LASEK (p = 0.01, 0.03, 0.04). Compared with FS-LASIK and LASEK, SMILE-treated eyes with high myopia had certain advantages in nerve density, length and nerve connection way and had better corneal transparency after operation.

Objective::To investigate the changes of corneal sub-basal nerve and corneal transparency in adolescents aged 8 to 15 years with orthokeratology lenses.Methods::In this prospective clinical study, myopic adolescents aged 8-15 years old fitted with orthokeratology lens in the Affiliated Hospital of Qingdao University from November 2020 to August 2021 were randomly selected. Nerve fiber density (NFD), nerve fiber length (NFL), nerve fiber orientation (NFO), and nerve fiber width (NFW) were assessed by confocal laser microscopy before and 1, 3 and 6 months after wearing lens. The optical density of cornea in different diameters was evaluated by Pentacam anterior segment analyzer. Pre- and post-wear comparisons of neuromorphological parameters and corneal optical density were performed using randomized zone group ANOVA.Results::A total of 16 patients (32 eyes) with myopia were included in the study, of which 4 were lost and 12 (28 eyes) eventually completed the follow-up. In the central cornea, the NFD was significantly increased at 1-month ( P=0.003) after wearing and gradually decreased to the baseline level at 3-and 6-month ( P>0.05). The difference in NFL shows no significant difference after lens wear ( P>0.05). NFO was significantly higher at 1 and 6 months ( P=0.015 and 0.047, respectively). NFW increased significantly at 6-month ( P=0.029). In the temporal cornea, there was no statistical difference during 6-month wearing ( P>0.05). NFL did not differ significantly during 6 months ( P>0.05). NFO increased gradually after wearing lens and showed statistical significance at 6 months ( P<0.001). NFW increased significantly at 3 months ( P=0.002) and further increased at 6 months ( P<0.001). In the upper cornea, NFD increased slightly in the early stage and decreased at 6-month, showing no statistical difference (all P>0.05). NFL increased significantly at 3-month ( P<0.001), and decreased to the baseline level at 6-month ( P>0.05). NFO significantly increased at 3 and 6 months ( P<0.001, P=0.022). The corneal optical density of the anterior corneal layer ≤2 mm and 2-6 mm increased at 6 months after wearing the lens, with statistical significance ( P=0.011, P<0.001). Conclusions::The morphology of the corneal sub-basal nerve and corneal densitometry changed significantly in the myopic adolescents after wearing orthokeratology lens. The nerve fiber density increased and then decreased after lens wearing, the degree of nerve course curvature increased, and the nerve fibers were generally thickened. The corneal transparency decreased steadily for 6 months after lens wearing.

Abstract Aims: This article aimed to assess the changes of subfoveal choroidal thickness (SFCT) in different follow-up durations for myopic children under the treatment of orthokeratology and give a reference for further studies.Method: Relevant publications were comprehensively retrieved through different databases, such as PubMed, Web of Science, Cochrane Library and Chinese database of Wan Fang and Wei Pu. Retrieval time was from the inception to February 2022. Standardized mean difference (SMD) and 95% confidence interval (95% CI) were selected as the effect for calculating and analyzing the changes of choroidal thickness in myopic children with orthokeratology.Result: A total of eight articles of 371 Patients (371 eyes) met our inclusion criteria. During the first month of wearing orthokeratology, choroidal thickness dramatically increased by 21.09 μ m (95%CI: 25.64, 16.7; P<0.00001). After the first month, it rose slightly, even became stable in next eleven months’ treatment (increased by 4.20 μm from the first month to the third month, 95%CI: 9.37, 0.9; P=0.11; increased by 3.99μm from the first month to the sixth month, 95%CI: 8.67, 0.6; P=0.09; increased by 2.99μm from the first month to the twelfth month, 95%CI: 7.76, 1.7; P=0.02).Conclusion: This meta-analysis demonstrated that in the first month with orthokeratology, choroidal thickness presented an obvious increase, after that it became stable or got a slightly rise for the longer following-up treatment.

Considering the significance of LINC01061 in papillary thyroid cancer, here, we commenced to study the role of LINC01061 in autoimmune thyroid disease (AITD) and the potential mechanism. Thyroid tissues were attained from patients with AITD, and Nthy-ori 3-1 cells were induced with lipopolysaccharide (LPS), followed by measurement of LINC01061, microRNA (miR)-612, and BRD4 expression as well as their binding relation. The ectopic expression and silencing experimentations were carried out in LPS-induced Nthy-ori 3-1 cells to detect cell viability and apoptosis as well as inflammation and inflammasome. BRD4 and LINC01061 upregulation and miR-612 downregulation were observed in thyroid tissues of AITD patients and LPS-induced Nthy-ori 3-1 cells. Mechanistic analysis manifested that LINC01061 bound to miR-612 that negatively targeted BRD4. LINC01061 upregulated BRD4 to enhance cell viability, trigger inflammation and inflammasome activation but reduce apoptosis of LPS-induced Nthy-ori 3-1 cells by sponging miR-612. In conclusion, LINC01061 induced the occurrence of AITD by upregulation of miR-612-mediated BRD4 expression.

Purpose: The biological role and mechanism of long noncoding RNA (lncRNA) myocardial infarction-associated transcript (MIAT) in dry eye remain to be illustrated. Pyroptosis is a noticeable form of inflammatory activation, which is characteristic of gasdermin D (GSDMD)-driven cell death. The present study was designed to explore the role of MIAT in pyroptosis and apoptosis induced by hyperosmolarity stress (HS) in human corneal epithelial cells (HCECs). Methods: HCECs were cultured in 70-120 mM hyperosmotic medium for 24 h to create a dry eye model in vitro. The level of the pyroptosis marker GSDMD was measured, and the cell inflammatory response was evaluated by detecting IL-113 and IL-18 levels. Exogenous caspase-1 inhibitor Ac-YVAD-CHO was used. The pyroptosis in HCECs was examined by caspase-1 activity, immunofluorescent staining, and Western blotting. Flow cytometry was performed to test the apoptosis rate of HCECs. Cell migration and proliferation were detected. The expression of the lncRNA MIAT in HCECs was detected by quantitative real-time PCR. MIAT was knocked down by small interfering RNA (siRNA) transfection. The effects of caspase-1 inhibition on pyroptosis, apoptosis, migration, and proliferation were observed. Results: HS promoted pyroptosis in HCECs by elevating caspase-1, GSDMD, and the active cleavage of GSDMD (N-terminal domain, N-GSDMD), and increased the release of IL-113, IL-18, LDH and the rate of apoptosis, with reduced cell migration. These changes were prevented by the inhibition of caspase-1. The expression of MIAT was significantly increased in HCECs exposed to a hyperosmotic medium. Silencing MIAT increased the expression of GSDMD, caspase-1, and inflammatory chemokines IL-113 and IL-18, and promoted apoptosis while inhibiting migration and proliferation in HCECs. Conclusion: The lncRNA MIAT is involved in HS-induced pyroptosis and apoptosis and the inflammatory response of HCECs and provides a new understanding of the pathogenesis of dry eye.

目的 探讨高度近视患者行飞秒激光小切口角膜基质透镜取出术(SMILE)、飞秒激光制瓣的准分子激光原位角膜磨镶术(FS-LASIK)以及准分子激光上皮瓣下角膜磨镶术(LASEK)术后不同时间不同直径范围内角膜光密度的对比及变化情况,及其与术中切削深度、切削厚度的相关性分析.方法 前瞻性队列研究.收集在青岛大学附属医院眼科就诊并进行屈光手术矫正的高度近视患者82例(164眼),按手术方式分为SMILE组30例(60眼);FS-LASIK组27例(54眼);LASEK组25例(50眼),于术前、术后1个月、术后3个月、术后6个月以及术后12个月行Pentacam三维眼前节分析系统检查,采用SPSS 22.0统计软件对术后同一时间不同术式角膜0～6 mm、>6～12 mm、整体直径范围内的角膜光密度采用随机区组方差分析,对术中切削深度、切削厚度与角膜光密度的关系采用Pearson相关分析.结果 术后1个月和术后6个月,不同组别患眼在同一直径范围内的角膜光密度相比差异均无统计学意义(均为P>0.05);术后3个月,LASEK组患眼的角膜光密度在0～6 mm、>6～12 mm、整体直径范围内均显著低于SMILE组,在>6～12 mm、整体直径范围内均显著低于FS-LASIK组(均为P<0.05);术后12个月,SMILE组患眼在0～6 mm、>6～12 mm、total直径范围内的角膜光密度均显著低于其他两组(均为P<0.05).术后3个月,0～6 mm、>6～12 mm、total直径范围内的角膜光密度与术中角膜切削深度、切削厚度均呈正相关(均为P<0.05);术后12个月,各直径范围内的角膜光密度与术中角膜切削深度、切削厚度均呈负相关(均为P<0.05).结论 高度近视患者在行激光角膜屈光术后的早期修复中,SMILE术式的角膜透明性稍差,而LASEK术式则相对更佳,但SMILE术后患眼长期的角膜透明性更佳.角膜光密度与术中角膜的切削深度以及切削厚度密切相关.

PURPOSE: To report three-decade changes of clinical characteristics, progress of treatments, and risk factors associated with mortality and enucleation in patients with retinoblastoma in China. DESIGN: Retrospective cohort study. METHODS: This multicenter study included 2552 patients diagnosed with retinoblastoma in 38 medical centers in 31 provinces in China from 1989 to 2017, with follow-up data. Kendall's tau-b value was used to describe correlation coefficients between the three eras (between 1989 and 2008, between 2009 and 2013, and between 2014 and 2017) and clinical or demographic features. Hazard ratios and odds ratios were applied to measure risk factors. RESULTS: A total of 324 (13%) patients died and 1414 (42%) eyes were removed. The 1-year, 3-year, and 5-year overall survival rates were 95%, 86%, and 83%, respectively. Patients were diagnosed at a better stage by International Classification for Retinoblastoma over time (Kendall's tau-b value = -0.084, P < .001). Pathological risk factors were also observed less in recent eras. New conservative therapies were adopted and used in more patients. The eye removal rate gradually decreased (Kendall's tau-b value = -0.167, P < .001). The over all survival rates were 81%, 83%, and 91% in the three eras. By multivariate Cox regression, bilateral tumors and extraocular extension were identified as risk factors for death. Among intraocular disease, Group E indicated higher risk of mortality. By multivariate logistics regression, unilateral tumors, earlier era of diagnosis, and extraocular extension were risk factors for eye salvage failure. Among intraocular retinoblastoma, Groups D and E had higher risk of eye salvage failure. CONCLUSIONS: Patients were diagnosed at an earlier stage in recent eras. Conservative therapies, including intra-arterial chemotherapy, were increasingly being used. The above changes may contribute to the decreasing enucleation rate. Although no significant impact was identified on the mortality by the three eras, a decreasing trend was shown. (C) 2021 Elsevier Inc. All rights reserved.

Background/purpose Proliferative diabetic retinopathy (PDR) is a major diabetic microvascular complication, characterized by pathological angiogenesis. This study sets out to investigate the potential molecular mechanism in the angiogenesis during PDR. Methods The expression of microRNA-30b (miR-30b) was quantified in a streptozotocin (STZ)-induced mouse model of PDR. The binding affinity between SIRT1 and miR-30b was then identified and validated. After transduction with In-miR-30b or combined with sh-SIRT1, high-glucose (HG)-induced retinal microvascular endothelial cells (RMECs) were co-cultured with extracellular vesicles (EVs) derived from the plasma of PDR mice (plasma-EVs). The proliferation and angiogenesis of RMECs were then detected in vitro. Results miR-30b expression was upregulated in the retinal tissue of PDR mice. SIRT1 was a target gene of miR-30b and under the negative regulation by miR-30b in RMECs. In contrast, inhibition of miR-30b resulted in elevated SIRT1 expression, thus alleviating the angiogenesis of RMECs. miR-30b was enriched in the plasma-EVs and could be delivered to RMECs, in which miR-30b exerted pro-angiogenic effects. Furthermore, inhibition of miR-30b arrested the progression of PDR in mice by promoting the expression of SIRT1. Conclusion Collectively, the present study pinpointed the involvement of miR-30b delivered by plasma-EVs in PDR angiogenesis, thus laying the basis for the development of novel therapeutic targets for the treatment of PDR.

Purpose: This study attempted to estimate the impact of eye-preserving therapies for the long-term prognosis of patients with advanced retinoblastoma with regard to overall survival and ocular salvage. Design: Retrospective cohort study covering all 31 provinces (38 retinoblastoma treating centers) of mainland China. Participants: One thousand six hundred seventy-eight patients diagnosed with group D or E retinoblastoma from January 2006 through May 2016. Methods: Chart review was performed. The patients were divided into primary enucleation and eye preserving groups, and they were followed up for survival status. The impact of initial treatment on survival was evaluated by Cox analyses. Main Outcome Measures: Overall survival and final eye preservation. Results: After a median follow-up of 43.9 months, 196 patients (12%) died, and the 5-year overall survival was 86%. In total, the eyeball preservation rate was 48%. In this cohort, 1172 patients (70%) had unilateral retinoblastoma, whereas 506 patients (30%) had bilateral disease. For patients with unilateral disease, 570 eyes (49%) underwent primary enucleation, and 602 patients (51%) received eye-preserving therapies initially. During the follow-up (median, 45.6 months), 59 patients (10%) from the primary enucleation group and 56 patients (9.3%) from the eye-preserving group died. Multivariate Cox analyses indicated no significant difference in overall survival between the 2 groups (hazard ratio [HR], 1.25; 95% confidence interval [CI], 0.85-1.84; P = 0.250). For patients with bilateral disease, 95 eyes (19%) underwent primary enucleation, and 411 patients (81%) received eye-preserving therapies initially. During the follow-up (median, 40.1 months), 12 patients (13%) from the primary enucleation group and 69 patients (17%) from the eye-preserving group died. For bilateral retinoblastoma with the worse eye classified as group E, patients undergoing primary enucleation exhibited better overall survival (HR, 2.35; 95% CI, 1.10-5.01; P = 0.027); however, this survival advantage was not evident until passing 22.6 months after initial diagnosis. Conclusions: Eye-preserving therapies have been used widely for advanced retinoblastoma in China. Patients with bilateral disease whose worse eye was classified as group E and who initially underwent eye preserving therapies exhibited a worse overall survival. The choice of primary treatment for advanced retinoblastoma should be weighed carefully. Ophthalmology 2022;129:209-219 (c) 2021 by the American Academy of Ophthalmology

Fucoidan is a marine-origin sulfated polysaccharide that has gained attention for its anticancer activities. However, the inhibitory effect of fucoidan on breast cancers by regulating autophagy and its mechanism are not clear, and the chemotherapeutic sensitization of fucoidan is largely unknown. In the present study, the anticancer potential of fucoidan was revealed in MCF-7 and MDA-MB-231 cells. Additionally, we also studied the chemotherapeutic sensitization of fucoidan by combining chemotherapeutic drugs doxorubicin (ADM) and cisplatin (DDP) with fucoidan on breast cancer cells. In the two kinds of human breast cancer cells, cell viability was determined by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. Apoptosis was examined with flow cytometry. Transfection assay was used to examine autophagy flow. Western blot was used to examine the expressions of related proteins. Results suggested that fucoidan could induce autophagy and might enhance the sensitivity of breast cancer cells to chemotherapeutic drugs. Mechanistically, fucoidan induced autophagy in breast cancer cells by down-regulating m-TOR/p70S6K/TFEB pathway. In conclusion, our research revealed that fucoidan could induce autophagy of breast cancer cells by mediating m-TOR/p70S6K/TFEB pathway, thus inhibiting tumor development. Furthermore, fucoidan might enhance the sensitivity of breast cancer cells to ADM and DDP, and this enhancement was related to autophagy.

Objective::To investigate the repair of corneal subepithelial nerve fibers in the early and middle stages after small incision lenticule extraction (SMILE), femtosecond flap excimer laser in situ keratomileusis (FS-LASIK) or laser epithelial keratomileusis (LASEK) in patients with high myopia.Methods::This was a prospective clinical study. Fifty-five patients (110 eyes) with high myopia who were treated in the Department of Ophthalmology at the Affiliated Hospital of Qingdao University were divided into a SMILE group (44 eyes), FS-LASIK group (36 eyes) and LASEK group (30 eyes). The repair of corneal nerve fibers was observed by laser confocal microscopy at 1, 3 and 6 months after the operations. Parameters of nerve fibers at different time periuds after the operations was used one-way ANOVA of random block design.Results::The corneal nerve distribution density, branch density, and length and width of different areas in patients with high myopia were best in the early stage after SMILE compared with the other two groups. The repair speed was also the fastest and reached the preoperative level earlier. Comparisons of corneal nerve repair in different areas, including the corneal flap, showed that the repair rate for FS-LASIK was between SMILE and LASEK. In the early stage after LASEK, especially in the central area, the white scar turbidity was obvious, and the speed and quality of corneal repair in different areas were the worst. The results of image analysis at the different time periods in each group suggested that the levels of corneal nerve fiber density (CNFD), corneal nerve fiber length (CNFL) and corneal nerve fiber total branch density (CTBD) in the center of the SMILE and FS-LASIK groups were significantly better than those in the LASEK group at 1 month after the operation (all P<0.05). The CNBD of SMILE was significantly better than that of both the FS-LASIK and LASEK groups ( HSD=4.367, P=0.007; HSD=4.237, P=0.008). Three months after the operation, the CNFD, CNBD, CNFL in the center of the SMILE operation were significantly better than for both the FS-LASIK and LASEK groups (all P<0.05). The CNFW of the LASEK operation was significantly better than that of both the SMILE and FS-LASIK groups ( HSD=3.457, P=0.003; HSD=3.668, P=0.004). Six months after the operation, the central CNFD, CNBD and CNFL of the SMILE operation were better than those of both the FS-LASIK and LASEK groups, and the difference was statistically significant (all P<0.05). Conclusions::In the early and middle stages after laser keratomileusis, SMILE is significantly superior to FS-LASIK and LASEK for nerve repair in all regions.