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Duration of Bare Sclera Pterygium Surgery Combined with Mitomycin C with and Without Tranexamic Acid: A Randomized Double-Blind Controlled Trial. 裸巩膜翼状胬肉手术联合使用丝裂霉素 C 和不使用氨甲环酸的持续时间:随机双盲对照试验。
IF 1.9 4区 医学 Q2 OPHTHALMOLOGY Pub Date : 2024-12-01 Epub Date: 2024-11-20 DOI: 10.1089/jop.2024.0068
Nevo Kovalis, Shmuel Graffi, Shadi Safuri, Yinon Shapira, Geulah Ben-David, Michael Mimouni

Purpose: To evaluate the efficacy of subconjunctival tranexamic acid (TXA) in reducing intraoperative bleeding, shortening surgery duration, and improving postoperative outcomes in pterygium surgery. Methods: In this double-blind, randomized controlled trial, 50 eyes of 50 patients undergoing pterygium surgery were randomly assigned to receive either subconjunctival injection of 0.25 mL of 5% TXA (TXA group, n = 25) or an equivalent volume of saline (control group, n = 25). Baseline characteristics, including age, gender, working environment, allergies, preoperative logMAR best-corrected visual acuity, and systemic anticoagulant or antiplatelet therapy, were similar between the groups. The primary outcome measures were intraoperative bleeding, surgery duration, and the number of eye spears used. Secondary outcome measures included postoperative visual acuity and pterygium recurrence rates at 3 years post-surgery. Results: No significant differences were observed between the TXA group and the control group in terms of surgery duration (445.3 ± 94.8 s vs. 423.5 ± 80.6 s, P = 0.40), the number of eye spears used (3.5 ± 2.4 vs. 3.5 ± 2.6, P = 0.97), or the weight of absorbed blood (1.94 ± 1.40 grams vs. 1.90 ± 1.25 grams, P = 0.91). Additionally, there were no significant differences in postoperative visual acuity (0.14 ± 0.13 logMAR vs. 0.20 ± 0.19 logMAR, P = 0.39) or pterygium recurrence rates at 3 years post-surgery (8.0% vs. 4.4%, P = 0.60). Subconjunctival TXA injection was safe, with no reported adverse events or complications associated with its use. Conclusion: Subconjunctival injection of TXA did not significantly reduce intraoperative bleeding, shorten surgery duration, or improve postoperative outcomes in pterygium surgery. The intervention was safe and well-tolerated, but further research is warranted to explore alternative interventions or modifications to the surgical technique that may improve outcomes in pterygium surgery.

目的:评估结膜下氨甲环酸(TXA)在翼状胬肉手术中减少术中出血、缩短手术时间和改善术后效果的效果。方法:在这项双盲随机对照试验中,接受翼状胬肉手术的 50 名患者的 50 只眼睛被随机分配到结膜下注射 0.25 mL 5%氨甲环酸(TXA 组,n = 25)或等量生理盐水(对照组,n = 25)。两组的基线特征相似,包括年龄、性别、工作环境、过敏史、术前最佳矫正视力 logMAR 值、全身抗凝剂或抗血小板治疗。主要结果指标为术中出血量、手术持续时间和使用的眼矛数量。次要结果指标包括术后视力和术后三年翼状胬肉复发率。结果:TXA组与对照组在手术时间(445.3 ± 94.8 秒 vs 423.5 ± 80.6 秒,P = 0.40)、眼矛使用数量(3.5 ± 2.4 vs 3.5 ± 2.6,P = 0.97)或吸收血液重量(1.94 ± 1.40 克 vs 1.90 ± 1.25 克,P = 0.91)方面无明显差异。此外,术后视力(0.14 ± 0.13 logMAR vs. 0.20 ± 0.19 logMAR,P = 0.39)或术后 3 年翼状胬肉复发率(8.0% vs. 4.4%,P = 0.60)均无明显差异。结膜下注射 TXA 是安全的,没有与使用 TXA 相关的不良事件或并发症报道。结论:结膜下注射 TXA 是安全的:结膜下注射 TXA 并不能明显减少翼状胬肉手术的术中出血、缩短手术时间或改善术后效果。该干预措施安全且耐受性良好,但仍需进一步研究,探索可改善翼状胬肉手术疗效的其他干预措施或手术技巧的改进方法。
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引用次数: 0
Cysteinyl Leukotriene Receptor Antagonism by Montelukast to Treat Visual Deficits. 用孟鲁司特拮抗胱氨酰白三烯受体治疗视力障碍
IF 1.9 4区 医学 Q2 OPHTHALMOLOGY Pub Date : 2024-12-01 Epub Date: 2024-10-02 DOI: 10.1089/jop.2024.0111
Amritha T M Seetharaman, Caroline E Owens, Rajashekhar Gangaraju

Montelukast, a Food and Drug Administration-approved drug for asthma and allergic rhinitis modulates leukotriene (LT) receptors and serves as a critical anti-inflammatory agent. Recent research suggests that the LT signaling pathway targeted by montelukast has broader implications for diseases such as fibrosis, cardiovascular diseases, cancer, cerebrovascular disease, and immune defense. This expanded understanding highlights montelukast's potential for repurposing in conditions involving aberrant stress mechanisms, including ocular diseases marked by inflammation, oxidative stress, ER stress, and apoptosis, among several others. This review delves into montelukast's therapeutic mechanisms across various diseases, draws parallels to ocular conditions, and examines clinical trials and associated adverse effects to underscore the unmet need for cysteinyl LT receptor antagonism by montelukast as an effective therapy for visual deficits.

孟鲁司特是美国食品和药物管理局批准的一种治疗哮喘和过敏性鼻炎的药物,它能调节白三烯(LT)受体,是一种重要的抗炎药物。最近的研究表明,孟鲁司特针对的 LT 信号通路对纤维化、心血管疾病、癌症、脑血管疾病和免疫防御等疾病具有更广泛的影响。对这一认识的扩展凸显了孟鲁司特在涉及异常应激机制的疾病(包括以炎症、氧化应激、ER 应激和细胞凋亡等为特征的眼部疾病)中重新使用的潜力。本综述深入探讨了孟鲁司特对各种疾病的治疗机制,将其与眼部疾病进行了比较,并研究了临床试验和相关不良反应,以强调通过孟鲁司特拮抗胱氨酰LT受体作为治疗视力障碍的有效疗法的需求尚未得到满足。
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引用次数: 0
Detection of Residual iPSCs Following Differentiation of iPSC-Derived Retinal Pigment Epithelial Cells. 检测 iPSC 衍生视网膜色素上皮细胞分化后的残余 iPSC。
IF 1.9 4区 医学 Q2 OPHTHALMOLOGY Pub Date : 2024-12-01 Epub Date: 2024-10-02 DOI: 10.1089/jop.2024.0130
Matthew Hill, Cynthia Andrews-Pfannkoch, Evan Atherton, Travis Knudsen, Emma Trncic, Alan D Marmorstein

Purpose: The goal of this study was to develop a lot release assay for iPSC residuals following directed differentiation of iPSCs to retinal pigment epithelial (RPE) cells. Methods: RNA Sequencing (RNA Seq) of iPSCs and RPE derived from them was used to identify pluripotency markers downregulated in RPE cells. Quantitative real time PCR (qPCR) was then applied to assess iPSC residuals in iPSC-derived RPE. The limit of detection (LOD) of the assay was determined by performing spike-in assays with known quantities of iPSCs serially diluted into an RPE suspension. Results: ZSCAN10 and LIN28A were among 8 pluripotency markers identified by RNA Seq as downregulated in RPE. Based on copy number and expression of pseudogenes and lncRNAs ZSCAN10 and LIN28A were chosen for use in qPCR assays for residual iPSCs. Reverse transcription PCR indicated generally uniform expression of ZSCAN10 and LIN28A in 21 clones derived from 8 iPSC donors with no expression of either in RPE cells derived from 5 donor lines. Based on qPCR, ZSCAN10, and LIN28A expression in iPSCs was generally uniform. The LOD for ZSCAN10 and LIN28A in qPCR assays was determined using spike in assays of RPE derived from 2 iPSC lines. Analysis of ΔΔCt found the limit of detection to be <0.01% of cells, equivalent to <1 iPSC/10,000 RPE cells in both iPSC lines. Conclusions: qPCR for ZSCAN10 and LIN28A detects <1 in 10,000 residual iPSCs in a population of iPSC-derived RPE providing an adequate LOD of iPSC residuals for lot release testing.

目的:本研究旨在开发一种批量释放检测方法,用于检测 iPSCs 定向分化为视网膜色素上皮细胞(RPE)后的 iPSCs 残留。方法:RNA 测序(RNA Sequencing):对 iPSCs 及其衍生的 RPE 进行 RNA 测序(RNA Seq),以确定 RPE 细胞中下调的多能性标记。然后应用定量实时 PCR (qPCR) 技术评估 iPSC 衍生的 RPE 中的 iPSC 残留。该检测方法的检测限 (LOD) 是通过将已知数量的 iPSCs 按一定比例稀释到 RPE 悬浮液中进行加标检测来确定的。结果通过 RNA Seq 鉴定,ZSCAN10 和 LIN28A 是在 RPE 中下调的 8 个多能性标记物之一。根据假基因和 lncRNA 的拷贝数和表达情况,ZSCAN10 和 LIN28A 被选中用于残留 iPSCs 的 qPCR 检测。反转录 PCR 显示,在来自 8 个 iPSC 供体的 21 个克隆中,ZSCAN10 和 LIN28A 的表达基本一致,而在来自 5 个供体系的 RPE 细胞中,两者均无表达。根据 qPCR,iPSCs 中 ZSCAN10 和 LIN28A 的表达基本一致。qPCR 检测中 ZSCAN10 和 LIN28A 的 LOD 是通过对 2 个 iPSC 品系的 RPE 进行尖峰检测确定的。对 ΔΔCt 的分析发现检测限为 结论:qPCR 检测 ZSCAN10 和 LIN28A 能检测出
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引用次数: 0
Effects of Rebamipide for Dry Eye on Optical Quality and Efficacy: A Systematic Review and Meta-Analysis. 瑞巴派特治疗干眼症对光学质量和疗效的影响:系统回顾与元分析》。
IF 1.9 4区 医学 Q2 OPHTHALMOLOGY Pub Date : 2024-12-01 Epub Date: 2024-10-25 DOI: 10.1089/jop.2024.0098
Yu-Ling Yan, Jing-Yao Chang, Xin-Ru Ling, Chun-Yan Xue

Purpose: To evaluate the effects of rebamipide ophthalmic suspension on optical quality and efficacy of patients with dry eye under different conditions. Methods: A comprehensive search across five databases (PubMed, Cochrane Library, Web of Science, China National Knowledge Infrastructure, and Wan Fang) was conducted for studies published through May 13, 2024, focusing on rebamipide for dry eye treatment. Results: A total of 11 studies including 334 patients with dry eye were included. Tear breakup time (TBUT) values of patients with dry eye increased significantly after 2 weeks (standardized mean difference [SMD] =1.07, 95% confidence interval [CI] = [0.05, 2.09]), 4 weeks (SMD = 1.26, 95% CI = [0.77, 1.75]), and 12 weeks (SMD = 1.04, 95% CI = [0.37, 1.71]) of rebamipide treatment. Subgroup analysis revealed that patients with dry eye wearing soft contact lens (SCL) exhibited higher TBUT values after 4 weeks of rebamipide treatment compared with those who received rebamipide alone. In addition, rebamipide significantly improved fluorescein staining score of patients with dry eye after 4 weeks of treatment (SMD = -0.34, 95% CI = [-0.63, -0.06]). However, 4 weeks of rebamipide treatment showed no significant effect on Schirmer I test values (SMD = -0.04, 95%, CI = [-0.43, 0.35]) and higher-order aberrations (SMD = -0.73, 95% CI = [-1.77, 0.30]). Conclusions: These results indicate a significant improvement in the efficacy of rebamipide treatment for patients with dry eye, particularly for those wearing SCL. The effect of rebamipide on visual quality was found to correlate with the underlying dry eye status.

目的:评估瑞巴派特眼用混悬液在不同条件下对干眼症患者光学质量和疗效的影响。方法在五个数据库(PubMed、Cochrane Library、Web of Science、中国国家知识基础设施和万方数据库)中对截至 2024 年 5 月 13 日发表的研究进行了全面检索,重点关注瑞巴派特用于干眼症治疗的研究。研究结果共纳入 11 项研究,包括 334 名干眼症患者。干眼症患者的泪液破裂时间(TBUT)值在接受瑞巴咪啶治疗 2 周(标准化平均差 [SMD] =1.07,95% 置信区间 [CI] = [0.05,2.09])、4 周(SMD =1.26,95% CI = [0.77,1.75])和 12 周(SMD =1.04,95% CI = [0.37,1.71])后显著增加。亚组分析显示,与单独接受瑞巴咪啶治疗的患者相比,佩戴软性隐形眼镜(SCL)的干眼症患者在接受 4 周瑞巴咪啶治疗后的 TBUT 值更高。此外,治疗 4 周后,干眼症患者的荧光素染色评分明显提高(SMD = -0.34,95% CI = [-0.63, -0.06])。然而,4周的雷帕米特治疗对Schirmer I测试值(SMD = -0.04,95% CI = [-0.43,0.35])和高阶像差(SMD = -0.73,95% CI = [-1.77,0.30])没有明显影响。结论:这些结果表明,对干眼症患者,尤其是佩戴 SCL 的干眼症患者而言,瑞贝美的疗效显著提高。研究发现,瑞巴派特对视觉质量的影响与干眼症的基本状况有关。
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引用次数: 0
Inflammation in Dry Eye Disease-Pathogenesis, Preclinical Animal Models, and Treatments. 干眼症中的炎症--发病机制、临床前动物模型和治疗方法。
IF 1.9 4区 医学 Q2 OPHTHALMOLOGY Pub Date : 2024-12-01 Epub Date: 2024-10-02 DOI: 10.1089/jop.2024.0103
Santosh Bhujbal, Ilva D Rupenthal, Philipp Steven, Priyanka Agarwal

Dry eye disease (DED) is a rapidly growing ocular surface disease with a significant socioeconomic impact that affects the patients' visual function and, thus, their quality of life. It is distinguished by a loss of tear film homeostasis, leading to tear film instability, hyperosmolarity, ocular surface inflammation, and neurosensory abnormalities, with all of these playing etiological roles in the propagation of the vicious DED circle. While current treatments primarily focus on reducing tear film instability and hyperosmolarity, increasingly more attention is being placed on tackling the underlying inflammation that propagates and potentiates these factors. As such, preclinical models are crucial to further elucidate the DED pathophysiology and develop novel therapeutic strategies. This review outlines the role of inflammation in DED, highlighting related signs and diagnostic tools before focusing on relevant preclinical animal models and potential therapeutic strategies to tackle DED-associated inflammation.

干眼症(DED)是一种迅速发展的眼表疾病,对社会经济产生重大影响,影响患者的视觉功能,进而影响他们的生活质量。它的特点是泪膜失去平衡,导致泪膜不稳定、高渗透性、眼表炎症和神经感觉异常,所有这些都是导致 DED 恶性循环的病因。虽然目前的治疗方法主要集中在降低泪膜不稳定性和高渗透性上,但越来越多的注意力放在了解决引发和加剧这些因素的潜在炎症上。因此,临床前模型对于进一步阐明 DED 病理生理学和开发新型治疗策略至关重要。本综述概述了炎症在 DED 中的作用,重点介绍了相关体征和诊断工具,然后重点介绍了相关的临床前动物模型和解决 DED 相关炎症的潜在治疗策略。
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引用次数: 0
Extracellular Vesicles Derived from Adipose-Derived Mesenchymal Stem Cells Alleviate Apoptosis and Oxidative Stress of Retinal Pigment Epithelial Cells Through Activation of Nrf2 Signaling Pathway. 源自脂肪间充质干细胞的细胞外囊泡通过激活 Nrf2 信号通路缓解视网膜色素上皮细胞的凋亡和氧化应激
IF 1.9 4区 医学 Q2 OPHTHALMOLOGY Pub Date : 2024-12-01 Epub Date: 2024-10-25 DOI: 10.1089/jop.2024.0064
Jin Sun Hwang, Hyun Beom Song, Geonhui Lee, Sangmoo Jeong, Dae Joong Ma

Purpose: To examine the potential protective effects of adipose-derived mesenchymal stem cell-derived extracellular vesicles (ASC-EVs) on ARPE-19 cells exposed to hydrogen peroxide (H2O2) stress and to evaluate their ability to delay retinal degeneration in Royal College of Surgeons (RCS) rats. Methods: ARPE-19 cells were pre-treated with ASC-EVs for 24 h, followed by exposure to 200 μM H2O2 for an additional 24 h. RCS rats received an intravitreal injection of phosphate-buffered saline in one eye and ASC-EVs in the other eye. Results: ASC-EV pretreatment significantly protected against H2O2 in the Cell Counting Kit-8 assay and was also effective in the lactate dehydrogenase-release assay. It notably reduced early apoptosis (Annexin V-fluorescein isothiocyanate/propidium iodide assay) and late apoptosis (Terminal Deoxynucleotidyl Transferase dUTP Nick End Labeling assay), while significantly decreasing intracellular reactive oxygen species, glutathione levels, and superoxide dismutase activity. NFE2L2, HMOX1, and NQO1 mRNA levels, along with Nrf2, HO-1, and NQO1 protein levels, were significantly elevated with ASC-EV pretreatment. Compared with ARPE-19-derived EVs, 11 miRNAs were upregulated and 34 were downregulated in ASC-EVs. In RCS rats, intravitreal injections of ASC-EVs led to significant preservation of the outer nuclear layer and photoreceptor segments, along with increased nuclear Nrf2 expression and elevated HO-1 and NQO1 levels in the inner retina. Eyes that received intravitreal injections of ASC-EVs demonstrated significantly preserved electroretinography a- and b-wave amplitudes at 1 week post-injection, though this effect faded by 2 weeks. Conclusions: ASC-EVs mitigated apoptosis and oxidative stress in ARPE-19 cells subjected to H2O2 exposure and temporarily slowed retinal degeneration in RCS rats via Nrf2 pathway activation by miRNAs.

目的:研究脂肪间充质干细胞衍生的细胞外囊泡(ASC-EVs)对暴露于过氧化氢(H2O2)应激的ARPE-19细胞的潜在保护作用,并评估其延缓皇家外科学院(RCS)大鼠视网膜变性的能力。方法:预处理 ARPE-19 细胞:一只眼睛接受磷酸盐缓冲盐水静脉注射,另一只眼睛接受ASC-EVs静脉注射。结果在细胞计数试剂盒-8测定中,ASC-EV预处理能明显抑制H2O2,在乳酸脱氢酶释放测定中也有效。它明显减少了早期细胞凋亡(Annexin V-荧光素异硫氰酸酯/碘化丙啶检测)和晚期细胞凋亡(末端脱氧核苷酸转移酶 dUTP Nick End Labeling 检测),同时显著降低了细胞内活性氧、谷胱甘肽水平和超氧化物歧化酶活性。经 ASC-EV 预处理后,NFE2L2、HMOX1 和 NQO1 mRNA 水平以及 Nrf2、HO-1 和 NQO1 蛋白水平均明显升高。与 ARPE-19 衍生的 EV 相比,ASC-EV 中有 11 个 miRNA 上调,34 个下调。在RCS大鼠中,玻璃体内注射ASC-EVs可显著保留核外层和感光节段,同时增加核Nrf2的表达,提高视网膜内层的HO-1和NQO1水平。注射ASC-EVs后1周,视网膜电图a波和b波振幅得到明显保护,但这种效果在2周后逐渐消失。结论ASC-EVs能减轻暴露于H2O2的ARPE-19细胞的凋亡和氧化应激,并通过miRNAs激活Nrf2通路暂时减缓RCS大鼠的视网膜退化。
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引用次数: 0
Eyes on New Product Development. 关注新产品开发。
IF 16.4 4区 医学 Q2 OPHTHALMOLOGY Pub Date : 2024-11-01 Epub Date: 2024-09-26 DOI: 10.1089/jop.2024.0155
Gary D Novack
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引用次数: 0
Efficacy and Safety of a Preservative-Free Latanoprost Cationic Emulsion in Patients with Open-Angle Glaucoma and Concurrent Ocular Surface Disease: A Randomized Phase 2 Study. 不含防腐剂的拉坦前列素阳离子乳剂对开角型青光眼和并发眼表疾病患者的疗效和安全性:随机 2 期研究。
IF 1.9 4区 医学 Q2 OPHTHALMOLOGY Pub Date : 2024-11-01 Epub Date: 2024-08-16 DOI: 10.1089/jop.2024.0029
Jason Bacharach, Eugene B McLaurin, Steven Silverstein, Mourad Amrane, Jean-Sebastien Garrigue, Dahlia Ismail, William J Flynn

Purpose: To compare intraocular pressure (IOP), ocular surface disease (OSD) parameters, and safety in patients with open-angle glaucoma (OAG)/ocular hypertension (OH) and concurrent OSD treated with preservative-free latanoprost 0.005% cationic emulsion (PF-latanoprost-E) or travoprost-Z 0.004% ophthalmical solution containing a soft preservative system. Methods: Patients with OAG/OH and OSD were randomized to treatment with PF-latanoprost-E or travoprost-Z nightly for 3 months. Outcomes included mean diurnal IOP reduction; OSD endpoints, including symptom improvement, tear break-up time (TBUT), and corneal fluorescein staining (CFS) score; and safety after 1 and 3 months. Results: A total of 105 patients were randomized, 51 to PF-latanoprost-E and 54 to travoprost-Z. IOP reductions (LS mean differences) at 3 months were numerically greater in the PF-latanoprost-E than in the travoprost-Z group at 8AM (7.2 versus 6.0 mmHg), 10AM (6.7 versus 5.9 mmHg), and 4PM (6.0 versus 5.4 mmHg). LS mean changes in IOP from baseline in both groups at 1 and 3 months, however, were comparable. Mean ± SD CFS scores on the Ora scale at month 3 showed significantly greater reductions in the PF-latanoprost-E than in the travoprost-Z group (-1.07 ± 1.863 versus -0.16 ± 2.553 P = 0.0461). The mean TBUT at month 3 showed similar improvements in both groups (1.1 versus 1.0 s, P > 0.05). OSD symptoms improved but did not differ significantly in the two groups. Overall safety was comparable in both groups. Conclusion: PF-latanoprost-E effectively and safely lowered IOP and improved OSD parameters in patients with OAG/OH. These findings provide evidence for the beneficial effects of this new formulation of latanoprost in glaucoma patients with OSD.

目的:比较开角型青光眼(OAG)/眼压过高(OH)并同时患有OSD的患者使用不含防腐剂的拉坦前列素0.005%阳离子乳剂(PF-拉坦前列素-E)或含有软防腐剂系统的曲伏前列素-Z 0.004%眼用溶液治疗时的眼压(IOP)、眼表疾病(OSD)参数和安全性。方法OAG/OH和OSD患者随机接受PF-拉坦前列素-E或曲伏前列素-Z治疗,每晚一次,为期3个月。结果包括平均昼间眼压降低率;OSD终点,包括症状改善、泪液破裂时间(TBUT)和角膜荧光素染色(CFS)评分;以及1个月和3个月后的安全性。结果共有105名患者接受了随机治疗,其中51人接受了PF-拉坦前列素-E治疗,54人接受了曲伏前列素-Z治疗。3 个月后,PF-拉坦前列腺素-E 组的眼压降低幅度(LS 平均差)在上午 8 点(7.2 毫米汞柱对 6.0 毫米汞柱)、上午 10 点(6.7 毫米汞柱对 5.9 毫米汞柱)和下午 4 点(6.0 毫米汞柱对 5.4 毫米汞柱)均高于曲伏前列腺素-Z 组。然而,两组患者在 1 个月和 3 个月后的眼压与基线相比的 LS 平均值变化不相上下。第 3 个月时,Ora 量表中 CFS 评分的平均值(± SD)显示,PF-拉坦前列素-E 组的降低幅度明显高于曲伏前列素-Z 组(-1.07 ± 1.863 对 -0.16 ± 2.553 P = 0.0461)。两组患者在第 3 个月时的平均 TBUT 改善情况相似(1.1 对 1.0 秒,P > 0.05)。OSD 症状有所改善,但两组差异不大。两组的总体安全性相当。结论PF-拉坦前列素-E能有效、安全地降低OAG/OH患者的眼压并改善OSD参数。这些发现为拉坦前列素这种新制剂在青光眼 OSD 患者中的有益作用提供了证据。
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引用次数: 0
Neuritin 1 Drives Therapeutic Preservation of Retinal Ganglion Cells in an Ex Vivo Human Glaucoma Model. Neuritin 1 在体外人类青光眼模型中驱动视网膜神经节细胞的治疗性保存。
IF 1.9 4区 医学 Q2 OPHTHALMOLOGY Pub Date : 2024-11-01 Epub Date: 2024-07-12 DOI: 10.1089/jop.2024.0041
Shahna S Hameed, Nicole E Bodi, Ryan C Miller, Tasneem P Sharma

Purpose: Glaucoma is a leading cause of irreversible blindness. Glaucomatous intraocular pressure (IOP) triggers deleterious effects, including gliosis, optic nerve (ON) axonal retraction, neurotrophic factor deprivation, inflammation, and other pathological events, leading to retinal ganglion cell (RGC) loss. Trophic factor impairment enhances RGC apoptosis susceptibility. Neuritin 1 (NRN1), a neurotrophic protein downstream of various neurotrophins, exhibited RGC protection and regeneration in axotomy models. We evaluated human recombinant NRN1's impact on human RGCs cultured in pressurized conditions within the ex vivo translaminar autonomous system to simulate glaucoma pathogenesis. Methods: Human glaucomatous and non-glaucomatous donor eyes were obtained from eye banks according to the Declaration of Helsinki. Initially, we evaluated NRN1and RGC marker expression in glaucoma and non-glaucomatous retina to determine the NRN1 level and its association with RGC loss. Further, we evaluated NRN1's therapeutic potential by treating pressurized human eyes at normal and high IOP for seven days. Retina, ON, and conditioned medium were analyzed for RGC survival (THY1, RBPMS), gliosis (GFAP), apoptosis (CASP3, CASP7), and extracellular matrix deposition (COLIV, FN) by qRT-PCR and western blotting. Paraphenylenediamine staining assessed ON axonal degeneration, whereas ex vivo electroretinogram assessed retinal activity. Results: Glaucomatous retinas exhibited significant reductions in both NRN1 (*p = 0.007, n = 5) and RGC marker expression (*p = 0.04, n = 5). NRN1 treatment reduced gliosis, extracellular matrix deposition, ON degeneration, and increased retinal activity in pressure-perfused eyes. Conclusions: Our study confirms that NRN1 enhances human RGC survival and improves retinal function in degenerative conditions, substantiating it as a promising candidate for rescuing human RGCs from degeneration.

目的:青光眼是导致不可逆失明的主要原因。青光眼眼压(IOP)会引发神经胶质细胞增生、视神经(ON)轴突回缩、神经营养因子匮乏、炎症和其他病理事件等有害影响,导致视网膜神经节细胞(RGC)丧失。营养因子受损会增加RGC凋亡的易感性。神经营养素1(NRN1)是多种神经营养素下游的一种神经营养蛋白,在轴突切断模型中表现出RGC的保护和再生能力。我们评估了人重组 NRN1 对在体外层间自主系统内加压条件下培养的人 RGC 的影响,以模拟青光眼的发病机制。方法:根据《赫尔辛基宣言》从眼库获取人类青光眼和非青光眼供体眼球。首先,我们评估了NRN1和RGC标记物在青光眼和非青光眼视网膜中的表达,以确定NRN1水平及其与RGC缺失的关系。此外,我们还通过在正常眼压和高眼压下对加压人眼进行为期七天的治疗,评估了 NRN1 的治疗潜力。我们通过 qRT-PCR 和 Western 印迹分析了视网膜、ON 和条件培养基中的 RGC 存活率(THY1、RBPMS)、胶质细胞增生(GFAP)、细胞凋亡(CASP3、CASP7)和细胞外基质沉积(COLIV、FN)。对苯二胺染色评估 ON 轴突变性,体外视网膜电图评估视网膜活动。结果青光眼视网膜中的NRN1(*p = 0.007,n = 5)和RGC标记表达(*p = 0.04,n = 5)均显著减少。NRN1 治疗可减少神经胶质增生、细胞外基质沉积、视网膜退化,并增加压力灌注眼的视网膜活动。结论我们的研究证实,NRN1 能提高人类 RGC 的存活率,并能改善退行性病变中的视网膜功能,因此它是拯救退行性病变中的人类 RGC 的理想候选物质。
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引用次数: 0
Comparative Ocular Pharmacokinetics of Dexamethasone Implants in Rabbits. 地塞米松植入物在兔子眼部的药代动力学比较。
IF 16.4 4区 医学 Q2 OPHTHALMOLOGY Pub Date : 2024-11-01 Epub Date: 2024-07-24 DOI: 10.1089/jop.2024.0052
Jihyun Won, Juhyung Kang, Wonku Kang

Purpose: Dexamethasone eye implant has been used to treat macular edema and non-infectious uveitis. To date, its ocular pharmacokinetics are not fully characterized, and the development of generic preparations is in progress, as the patent of the original brand expires soon. Therefore, this work was designed to 1) determine the time course of vitreous dexamethasone concentrations following intravitreal implantation in rabbits and 2) explore the alternative use of NDF-SI01 from a pharmacokinetic point of view compared to Ozurdex®, which is currentlyused in the market. Methods: Ozurdex® and NDF-SI01 were implanted into the right and left eyes of the rabbit, respectively. A serial vitreous collection was performed to minimize the sacrifice of animals, and dexamethasone concentrations were measured by HP LC-MS/MS. Results: After implantation, dexamethasone concentration reaches the maximum concentration (3.1 μg/mL) in 19.5 days and decreases with a half-life of 40.3 h. AUC and clearance are 683.9 μg·h/mL and 1.29 mL/h, respectively. There is no significant difference in pharmacokinetic parameters between NDF-SI01 and Ozurdex®. The overall patterns of the cumulative release of both implants are similar. Conclusions: NDF-SI01 could alternate Ozurdex® in clinics based on the in vivo comparative pharmacokinetic study and in vitro dissolution test.

目的:地塞米松眼药已被用于治疗黄斑水肿和非感染性葡萄膜炎。迄今为止,地塞米松的眼部药代动力学尚未完全定型,而且由于原品牌的专利即将到期,非专利制剂的开发也在进行中。因此,本研究的目的是:1)确定兔子玻璃体内植入地塞米松后玻璃体内地塞米松浓度的时间过程;2)从药代动力学的角度探讨与目前市场上使用的 Ozurdex® 相比,NDF-SI01 的替代用途。方法:将 Ozurdex® 和 NDF-SI01 分别植入兔子的右眼和左眼。为了尽量减少动物的牺牲,对玻璃体进行了连续采集,并通过 HP LC-MS/MS 测定了地塞米松的浓度。结果植入后,地塞米松的浓度在 19.5 天内达到最大值(3.1 μg/mL),然后以 40.3 小时的半衰期下降,AUC 和清除率分别为 683.9 μg-h/mL 和 1.29 mL/h。NDF-SI01 和 Ozurdex® 的药代动力学参数没有明显差异。两种植入物累积释放的总体模式相似。结论根据体内比较药代动力学研究和体外溶解试验,NDF-SI01 可以在临床上替代 Ozurdex®。
{"title":"Comparative Ocular Pharmacokinetics of Dexamethasone Implants in Rabbits.","authors":"Jihyun Won, Juhyung Kang, Wonku Kang","doi":"10.1089/jop.2024.0052","DOIUrl":"10.1089/jop.2024.0052","url":null,"abstract":"<p><p><b><i>Purpose:</i></b> Dexamethasone eye implant has been used to treat macular edema and non-infectious uveitis. To date, its ocular pharmacokinetics are not fully characterized, and the development of generic preparations is in progress, as the patent of the original brand expires soon. Therefore, this work was designed to 1) determine the time course of vitreous dexamethasone concentrations following intravitreal implantation in rabbits and 2) explore the alternative use of NDF-SI01 from a pharmacokinetic point of view compared to Ozurdex<sup>®</sup>, which is currentlyused in the market. <b><i>Methods:</i></b> Ozurdex<sup>®</sup> and NDF-SI01 were implanted into the right and left eyes of the rabbit, respectively. A serial vitreous collection was performed to minimize the sacrifice of animals, and dexamethasone concentrations were measured by HP LC-MS/MS. <b><i>Results:</i></b> After implantation, dexamethasone concentration reaches the maximum concentration (3.1 μg/mL) in 19.5 days and decreases with a half-life of 40.3 h. AUC and clearance are 683.9 μg·h/mL and 1.29 mL/h, respectively. There is no significant difference in pharmacokinetic parameters between NDF-SI01 and Ozurdex<sup>®</sup>. The overall patterns of the cumulative release of both implants are similar. <b><i>Conclusions:</i></b> NDF-SI01 could alternate Ozurdex<sup>®</sup> in clinics based on the in vivo comparative pharmacokinetic study and in vitro dissolution test.</p>","PeriodicalId":16689,"journal":{"name":"Journal of Ocular Pharmacology and Therapeutics","volume":" ","pages":"608-614"},"PeriodicalIF":16.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141759314","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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Journal of Ocular Pharmacology and Therapeutics
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