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Cost-Effectiveness Analysis of Adalimumab Versus Cyclosporine for Vogt-Koyanagi-Harada Disease: A Randomized Controlled Study. 阿达木单抗与环孢素治疗Vogt-Koyanagi-Harada病的成本效益分析:随机对照研究
IF 1.7 4区 医学 Q3 OPHTHALMOLOGY Pub Date : 2024-10-01 Epub Date: 2024-05-23 DOI: 10.1080/02713683.2024.2355659
Lingyu Dai, Zhenyu Zhong, Qiuying Wu, Yu Gao, Xiaorong Lu, Fuxiang Zhang, Chong Tang, Yao Wang, Chunjiang Zhou, Peizeng Yang

Purpose: To compare the 26-week cost-effectiveness of adalimumab-corticosteroids (ADA-CS) and cyclosporine-corticosteroids (CSA-CS) for Vogt-Koyanagi-Harada (VKH).

Methods: A preplanned cost-effectiveness analysis based on the per-protocol population of a randomized-controlled trial. VKH subjects were randomized to receive either cyclosporine (100-200 mg daily) combined with corticosteroids or adalimumab (40 mg twice monthly) combined with corticosteroids. The primary outcome of this cost-effectiveness study was the incremental cost-effectiveness ratio (ICER). Costs and quality-adjusted life-years (QALYs) data were calculated by the medical records and health utility, respectively. Subgroup (early and late-phase VKH) analysis and sensitivity analyses were performed.

Results: The ICER at 26 weeks was $62,425/QALY for the total participants. Compared to the CSA-CS group, costs in the ADA-CS group were more expensive (mean difference [ΔA-C]: $2,497) with more gains in QALYs (mean difference [ΔA-C]: 0.04). The probability of ADA-CS being cost-effective was 0.17 and 0.41 at willingness to pay (WTP) thresholds of $12,000/QALY and $36,000/QALY, respectively. Subgroup analysis and sensitivity analyses showed consistent findings with the primary analysis.

Conclusions: Regardless of early or late-phase VKH, the CSA-CS strategy may be recommended as the preferred initial choice for the majority of VKH.

目的:比较阿达木单抗-皮质类固醇(ADA-CS)和环孢素-皮质类固醇(CSA-CS)治疗Vogt-Koyanagi-Harada(VKH)26周的成本效益:方法:根据随机对照试验的按方案人群进行预先计划的成本效益分析。VKH受试者被随机分配接受环孢素(每天100-200毫克)联合皮质类固醇激素或阿达木单抗(每月两次,每次40毫克)联合皮质类固醇激素治疗。这项成本效益研究的主要结果是增量成本效益比(ICER)。成本和质量调整生命年(QALYs)数据分别由医疗记录和健康效用计算得出。进行了亚组(早期和晚期 VKH)分析和敏感性分析:所有参与者在 26 周时的 ICER 为 62,425 美元/QALY。与 CSA-CS 组相比,ADA-CS 组的成本更昂贵(平均差异[ΔA-C]:2,497 美元),但 QALYs 收益更高(平均差异[ΔA-C]:0.04)。在支付意愿(WTP)阈值为 12,000 美元/QALY 和 36,000 美元/QALY 时,ADA-CS 具有成本效益的概率分别为 0.17 和 0.41。分组分析和敏感性分析结果与主要分析结果一致:无论 VKH 是早期还是晚期,CSA-CS 策略均可作为大多数 VKH 的首选初始方案。
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引用次数: 0
A Standardized Extract of Green-Cotyledon Small Black Soybean (EYESOY®) Ameliorates Dry Eye Syndrome in an Animal Model. 绿子叶小粒黑大豆的标准化提取物 (EYESOY®) 可改善动物模型的干眼症。
IF 1.7 4区 医学 Q3 OPHTHALMOLOGY Pub Date : 2024-10-01 Epub Date: 2024-06-10 DOI: 10.1080/02713683.2024.2357599
Yoonhee Lee, Juyeon Park, Sunah Bang, Yongbum Kwon

Purpose: Dry eye syndrome is a common ocular disease that causes morbidity, high healthcare burden, and decreased quality of life. In this study, we evaluated the beneficial effects of a standardized extract of small black soybean (EYESOY®) in a benzalkonium chloride (BAC)-induced murine model of dry eye.

Methods: Experimental dry eye was induced by instillation of 0.02% BAC on the right eye of the Sprague-Dawley rats. Saline solution or EYESOY were administered orally every day for 8 weeks.

Results: EYESOY significantly improved tear volume in the cornea compared with that in the BAC group. Moreover, EYESOY inhibited damage to the corneal epithelial cells and lacrimal glands by suppressing the oxidative and inflammatory responses in a mouse dry eye model. It also increased the goblet cell density and mucin integrity in the conjunctiva.

Conclusions: Our results suggest that EYESOY has the potential to alleviate dry eye syndrome.

目的:干眼症是一种常见的眼部疾病,会导致发病率、高医疗负担和生活质量下降。在这项研究中,我们评估了小粒黑豆标准化提取物(EYESOY®)在苯扎氯铵(BAC)诱导的小鼠干眼症模型中的有益作用:方法:在 Sprague-Dawley 大鼠的右眼中注入 0.02% 的苯扎氯铵,诱发实验性干眼症。连续 8 周每天口服生理盐水或 EYESOY:结果:与 BAC 组相比,EYESOY 能明显改善角膜的泪液量。此外,在小鼠干眼症模型中,EYESOY 通过抑制氧化和炎症反应,抑制了对角膜上皮细胞和泪腺的损伤。结论:我们的研究结果表明,"EYESOY "对小鼠干眼症模型中的角膜上皮细胞和泪腺的损伤有抑制作用,同时还能增加结膜中的鹅口疮细胞密度和粘蛋白完整性:我们的研究结果表明,EYESOY 具有缓解干眼症的潜力。
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引用次数: 0
Dysfunction of Endothelial Cell-Mediated Intercellular Communication and Metabolic Pathways in Age-Related Macular Degeneration. 老年性黄斑变性中内皮细胞介导的细胞间通信和代谢途径的功能障碍。
IF 1.7 4区 医学 Q3 OPHTHALMOLOGY Pub Date : 2024-09-27 DOI: 10.1080/02713683.2024.2407361
Yang Li, Rong Zhang, Jing Li, Lin Wang, Guohong Zhou

Purpose: Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly, but the therapies are not satisfactory. This study aimed to find AMD specific features through the analysis of high-throughput sequencing.

Methods: In this study, we integrated six projects containing single-cell RNA sequencing (scRNA-seq) data to perform a comprehensive analysis for AMD samples in the tissues of retina and retinal pigment epithelium/choroid, and in the positions of macula and periphery. Differentially expressed genes (DEGs) were analyzed and crucial signaling pathways were identified across cell types and between the macula and periphery. The intercellular signaling transduction among cell types were inferred by "CellChat" to build cell-cell communication network under normal and AMD conditions, and verified at the transcriptional level. The CD31+ endothelial cells were obtained to evaluate the enrichment of KEGG pathways in atrophic and neovascular AMD, and GSVA was adopted to discover differential metabolic signals in each AMD type.

Results: Thirteen major cell types were identified in the integrated scRNA-seq data. Although no disease-specific cell type or differential cell proportion was found, DEGs and enriched pathways were shown in cell-type- and position-dependent manners. Severe impairment of endothelial cell-mediated cell interactions was found in the signaling transduction network of the macula, and compromised cell interactions were observed in the periphery. Furthermore, distinct signaling pathways and metabolic states were uncovered in atrophic and neovascular AMD. Striking reduction in energy metabolism, lipid metabolism, and oxidative stress was indicated in the atrophic AMD.

Conclusion: Conclusively, we discover aberrant signals and metabolic pathways in AMD samples, providing insight into mechanisms and potential therapeutic targets for the AMD treatment.

{"title":"Dysfunction of Endothelial Cell-Mediated Intercellular Communication and Metabolic Pathways in Age-Related Macular Degeneration.","authors":"Yang Li, Rong Zhang, Jing Li, Lin Wang, Guohong Zhou","doi":"10.1080/02713683.2024.2407361","DOIUrl":"https://doi.org/10.1080/02713683.2024.2407361","url":null,"abstract":"<p><strong>Purpose: </strong>Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly, but the therapies are not satisfactory. This study aimed to find AMD specific features through the analysis of high-throughput sequencing.</p><p><strong>Methods: </strong>In this study, we integrated six projects containing single-cell RNA sequencing (scRNA-seq) data to perform a comprehensive analysis for AMD samples in the tissues of retina and retinal pigment epithelium/choroid, and in the positions of macula and periphery. Differentially expressed genes (DEGs) were analyzed and crucial signaling pathways were identified across cell types and between the macula and periphery. The intercellular signaling transduction among cell types were inferred by \"CellChat\" to build cell-cell communication network under normal and AMD conditions, and verified at the transcriptional level. The CD31+ endothelial cells were obtained to evaluate the enrichment of KEGG pathways in atrophic and neovascular AMD, and GSVA was adopted to discover differential metabolic signals in each AMD type.</p><p><strong>Results: </strong>Thirteen major cell types were identified in the integrated scRNA-seq data. Although no disease-specific cell type or differential cell proportion was found, DEGs and enriched pathways were shown in cell-type- and position-dependent manners. Severe impairment of endothelial cell-mediated cell interactions was found in the signaling transduction network of the macula, and compromised cell interactions were observed in the periphery. Furthermore, distinct signaling pathways and metabolic states were uncovered in atrophic and neovascular AMD. Striking reduction in energy metabolism, lipid metabolism, and oxidative stress was indicated in the atrophic AMD.</p><p><strong>Conclusion: </strong>Conclusively, we discover aberrant signals and metabolic pathways in AMD samples, providing insight into mechanisms and potential therapeutic targets for the AMD treatment.</p>","PeriodicalId":10782,"journal":{"name":"Current Eye Research","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142343123","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
Investigating the Link between Psychological Well-Being and Early-Stage Age-Related Macular Degeneration: A Mendelian Randomization Analysis.
IF 1.7 4区 医学 Q3 OPHTHALMOLOGY Pub Date : 2024-09-27 DOI: 10.1080/02713683.2024.2408757
Jie Deng, YuHui Qin

Purpose: While some studies have started to focus on the link between psychological well-being and age-related macular degeneration (AMD), the relationship remains uncertain. Our research aims to provide new insights into this association, laying a foundation for future interventions and addressing existing knowledge gaps.

Methods: We utilized the "TwoSampleMR" package in R for a bidirectional Mendelian randomization analysis of psychological well-being (subjective well-being, depression, neuroticism, and Sensitivity to Environmental Stress and Adversity) and early-stage AMD. Causal effects were estimated using the inverse-variance weighted method, and additional methods included weighted median and MR-Egger regression. Sensitivity analyses included Cochran's Q test, MR-Egger intercept analysis, MR-PRESSO, and leave-one-out analysis.

Results: The study found that the population with genetic predisposition to neuroticism had a 39.7% lower risk of early-stage AMD (OR = 0.603, 95% CI = 0.385-0.945, p = 0.027). Conversely, the population with genetic predisposition to subjective well-being had a 3.2% increased risk of early-stage AMD (OR = 1.032, 95% CI = 1.003-1.063, p = 0.029). No significant causal relationships were found from depression or Sensitivity to Environmental Stress and Adversity to early-stage AMD, nor from early-stage AMD to psychological well-being.

Conclusion: This study provides preliminary evidence that the relationship between psychological well-being and early-stage AMD may be complex and multifaceted. It suggests that moderate neuroticism levels might reduce early-stage AMD risk through health behaviors, pathophysiological mechanisms, and other factors, while high subjective well-being levels might increase this risk similarly. However, these findings are insufficient for preventive strategies due to a lack of substantial evidence and still require extensive experimental research for further validation.

目的:虽然一些研究已经开始关注心理健康与老年性黄斑变性(AMD)之间的联系,但这种关系仍然不确定。我们的研究旨在为这一关系提供新的见解,为未来的干预措施奠定基础,并解决现有的知识空白:我们利用 R 软件包 "TwoSampleMR "对心理健康(主观幸福感、抑郁、神经质以及对环境压力和逆境的敏感性)和早期 AMD 进行了双向孟德尔随机分析。因果效应采用逆方差加权法进行估计,其他方法包括加权中位数和MR-Egger回归。敏感性分析包括 Cochran's Q 检验、MR-Egger 截距分析、MR-PRESSO 和遗漏分析:研究发现,具有神经质遗传倾向的人群罹患早期 AMD 的风险降低了 39.7%(OR = 0.603,95% CI = 0.385-0.945,p = 0.027)。相反,具有主观幸福感遗传倾向的人群患早期老年性黄斑变性的风险增加了 3.2%(OR = 1.032,95% CI = 1.003-1.063,p = 0.029)。没有发现抑郁或对环境压力和逆境的敏感性与早期老年性黄斑变性有明显的因果关系,也没有发现早期老年性黄斑变性与心理健康有明显的因果关系:本研究提供的初步证据表明,心理健康与早期老年性视网膜病变之间的关系可能是复杂和多方面的。它表明,中等程度的神经质可能会通过健康行为、病理生理机制和其他因素降低早期 AMD 的风险,而高水平的主观幸福感可能会同样增加这种风险。然而,由于缺乏实质性证据,这些发现还不足以制定预防策略,仍需要广泛的实验研究来进一步验证。
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引用次数: 0
Effect Modifiers and Risk Factors of Intraocular Inflammation Following Brolucizumab: A Systematic Review and Meta-analysis. 布卢珠单抗后眼内炎症的效应调节因子和风险因素:系统回顾与元分析》。
IF 1.7 4区 医学 Q3 OPHTHALMOLOGY Pub Date : 2024-09-25 DOI: 10.1080/02713683.2024.2402319
Hashem Abu Serhan, Amr K Hassan, Mohamed Rifai, Rowayda A Elsayed, Chakib Djeffal, Yasmine Cherif, Kamel Aboujabal, Nour Awamleh, Merlyn Anjali Pereira, Saket Arya, Abdelrahman M Anter, Ayman G Elnahry

Purpose: To identify risk factors and effect modifiers associated with intraocular inflammation (IOI) following brolucizumab injection.

Methods: Our protocol was registered on PROSPERO (CRD42022382645). We searched six electronic databases (PubMed, Scopus, Web of Science, CENTRAL, EMBASE, and Google Scholar) to retrieve all studies that reported the occurrence of IOI following brolucizumab. Data are reported as mean difference with their corresponding 95% confidence intervals. All analyses were conducted per eye, and the risk of bias was assessed using the National Health Institute tool.

Results: Our analysis included 3527 eyes of 3469 patients of 33 papers. The mean age of the patients was 74 years (SD = 10.9, Range = 62.3-80.9). There were 1793 male patients (51.7%) and 1719 female patients (49.6%). The average follow-up period was 13.9 months (SD = 9.4). The mean number of injections was 4.5 (SD = 2.9) injections per eye; 1315 (37.3%) eyes had neovascular AMD, 189 (5.4%) had diabetic macular edema, and 129 (3.7%) eyes had polypoidal choroidal vasculopathy. Post-intervention, subretinal fluid, intraretinal fluid, and pigment epithelial detachment were significantly improved (46.5-11.3% of patients, 55.7-11.3% of patients, 24.7-7.1% of patients, respectively) (p < 0.001). Regarding visual acuity, there was an improvement with a mean difference of 0.12 (95% CI = 0.18-0.07, z = 4.38, p < 0.0001, 2064 eyes). The most common reported complication is IOI (n = 196, 6%). IOI was observed more in the elderly (76.3 ± 9.2 years), females (66%), and after the second injection.

Conclusions: This systematic review provides valuable insights into risk factors and effect modifiers for IOI associated with brolucizumab treatment, aiding clinicians in optimizing patient care. Future studies should prioritize prospective, long-term investigations to further elucidate the safety profile of brolucizumab and refine its use in the management of retinal and choroidal vascular diseases.

{"title":"Effect Modifiers and Risk Factors of Intraocular Inflammation Following Brolucizumab: A Systematic Review and Meta-analysis.","authors":"Hashem Abu Serhan, Amr K Hassan, Mohamed Rifai, Rowayda A Elsayed, Chakib Djeffal, Yasmine Cherif, Kamel Aboujabal, Nour Awamleh, Merlyn Anjali Pereira, Saket Arya, Abdelrahman M Anter, Ayman G Elnahry","doi":"10.1080/02713683.2024.2402319","DOIUrl":"https://doi.org/10.1080/02713683.2024.2402319","url":null,"abstract":"<p><strong>Purpose: </strong>To identify risk factors and effect modifiers associated with intraocular inflammation (IOI) following brolucizumab injection.</p><p><strong>Methods: </strong>Our protocol was registered on PROSPERO (CRD42022382645). We searched six electronic databases (PubMed, Scopus, Web of Science, CENTRAL, EMBASE, and Google Scholar) to retrieve all studies that reported the occurrence of IOI following brolucizumab. Data are reported as mean difference with their corresponding 95% confidence intervals. All analyses were conducted per eye, and the risk of bias was assessed using the National Health Institute tool.</p><p><strong>Results: </strong>Our analysis included 3527 eyes of 3469 patients of 33 papers. The mean age of the patients was 74 years (SD = 10.9, Range = 62.3-80.9). There were 1793 male patients (51.7%) and 1719 female patients (49.6%). The average follow-up period was 13.9 months (SD = 9.4). The mean number of injections was 4.5 (SD = 2.9) injections per eye; 1315 (37.3%) eyes had neovascular AMD, 189 (5.4%) had diabetic macular edema, and 129 (3.7%) eyes had polypoidal choroidal vasculopathy. Post-intervention, subretinal fluid, intraretinal fluid, and pigment epithelial detachment were significantly improved (46.5-11.3% of patients, 55.7-11.3% of patients, 24.7-7.1% of patients, respectively) (<i>p</i> < 0.001). Regarding visual acuity, there was an improvement with a mean difference of 0.12 (95% CI = 0.18-0.07, <i>z</i> = 4.38, <i>p</i> < 0.0001, 2064 eyes). The most common reported complication is IOI (<i>n</i> = 196, 6%). IOI was observed more in the elderly (76.3 ± 9.2 years), females (66%), and after the second injection.</p><p><strong>Conclusions: </strong>This systematic review provides valuable insights into risk factors and effect modifiers for IOI associated with brolucizumab treatment, aiding clinicians in optimizing patient care. Future studies should prioritize prospective, long-term investigations to further elucidate the safety profile of brolucizumab and refine its use in the management of retinal and choroidal vascular diseases.</p>","PeriodicalId":10782,"journal":{"name":"Current Eye Research","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142343124","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
Analysis of Prognostic Factors and Treatment Outcomes in Indirect Traumatic Optic Neuropathy: A Retrospective Review of 105 Patients. 间接创伤性视神经病变的预后因素和治疗结果分析:105例患者的回顾性研究
IF 1.7 4区 医学 Q3 OPHTHALMOLOGY Pub Date : 2024-09-23 DOI: 10.1080/02713683.2024.2404599
Zhihua Cheng, Fulin Xu, Min Gao, Yongyan Bi, Ye Jiang, Lutao Yuan, Shaoshuai Wu, Cong Luo

Purpose: To identify risk factors for vision recovery in indirect traumatic optic neuropathy (TON) and to analyze the outcomes associated with surgical treatment for TON.

Methods: Between 2020 and 2023, a total of 105 patients diagnosed with traumatic optic neuropathy (TON) at Shanghai Ninth People's Hospital and Shanghai Minhang Hospital were included in a retrospective study. These individuals underwent optic nerve decompression surgery as part of their treatment. To collect comprehensive data, both preoperative and postoperative information was gathered. For analytical purposes, only those patients who had a minimum of one month follow-up post-treatment were considered. The statistical analysis incorporated the use of median values, odds ratios (OR), and 95% confidence intervals (CI) to interpret the data. Any p-values less than 0.05 were deemed to indicate statistical significance, underlining the rigorous criteria set for this study.

Results: A total of 105 patients, with a mean age of 31.8 ± 14.9 years, met the inclusion criteria; 89.5% (94) were men, and 10.5% (11) were women. The median time to seek medical attention after injury was 4 days (range: 1 to 15 days). Prognostic factors associated with visual acuity (VA) improvement included a gradual VA loss pattern (OR: 2.22, 95% CI: 0.91-5.67, p = 0.045), while canal fractures (OR: 0.31, 95% CI: 0.095-0.933, p = 0.019) significantly correlated with poor VA outcomes.

Conclusions: This study suggested that surgical interventions benefit TON patients with low vision. Gradual VA loss, rather than sudden loss after injury, may be a potential prognostic factor for favorable VA outcomes, while canal fractures, as detected on computed tomography (CT) imaging-especially complex canal fractures, are associated with poor VA outcomes. In the future, more definitive prospective treatment trials are required to identify optimal treatment strategies for TON.

目的:确定间接创伤性视神经病变(TON)视力恢复的风险因素,并分析TON手术治疗的相关结果:2020年至2023年期间,上海市第九人民医院和上海闵行医院共收治了105名被诊断为外伤性视神经病变(TON)的患者。这些患者接受了视神经减压手术作为治疗的一部分。为了收集全面的数据,研究人员收集了术前和术后的信息。为了便于分析,只考虑了治疗后至少随访一个月的患者。统计分析采用中位值、几率比(OR)和 95% 置信区间(CI)来解释数据。任何小于 0.05 的 p 值都被视为具有统计学意义,这凸显了本研究设定的严格标准:共有 105 名患者符合纳入标准,平均年龄(31.8±14.9)岁;其中 89.5%(94 人)为男性,10.5%(11 人)为女性。受伤后就医时间的中位数为 4 天(范围:1 至 15 天)。与视力(VA)改善相关的预后因素包括VA逐渐丧失模式(OR:2.22,95% CI:0.91-5.67,p = 0.045),而眼管骨折(OR:0.31,95% CI:0.095-0.933,p = 0.019)与VA不良结果显著相关:这项研究表明,手术干预有利于视力低下的东京近视患者。而计算机断层扫描(CT)成像发现的视管骨折,尤其是复杂的视管骨折,则与视力低下的预后相关。未来,需要进行更多明确的前瞻性治疗试验,以确定TON的最佳治疗策略。
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引用次数: 0
Temporal Regulation of Myopia and Inflammation-Associated Pathways in the Interphotoreceptor Retinoid-Binding Protein Knockout Mouse Model. 光感受器间视黄醇结合蛋白基因敲除小鼠模型中近视和炎症相关途径的时间调控
IF 1.7 4区 医学 Q3 OPHTHALMOLOGY Pub Date : 2024-09-23 DOI: 10.1080/02713683.2024.2402317
Shanu Markand, Somin Kim, Micah A Chrenek, Salma Ferdous, Priyanka Priyadarshani, Jeffrey H Boatright, John M Nickerson

Purpose: Myopia is a complex disorder with etiology involving an interplay between several genetic and environmental factors. Interphotoreceptor retinoid-binding protein (IRBP) is found in the subretinal space and is crucial in the visual cycle. The interphotoreceptor retinoid-binding protein knockout mouse (IRBP KO) was established as a model system to understand myopia and retinal degeneration. The current study investigated genes associated with myopia, retinal homeostasis, and inflammation in IRBP KO.

Methods: RNA from retinas of congenic IRBP KO and wild-type C57BL/6J (WT) mice at postnatal day 5 (P5), P40, and P213 were subjected to digital droplet PCR (ddPCR) using a Bio-Rad automated droplet generator and QX200 reader. Target genes were selected based on genome-wide association studies, animal models, myopia studies, and other genes associated with retinal homeostasis and inflammation. HPRT, a housekeeping gene, was used for normalization. An average expression ratio (target/HPRT) and standard deviation (SD) were calculated. ANOVA assessed statistical significance, and a p < 0.05 was considered significant.

Results: The ddPCR data analysis indicated that numerous myopia and inflammation-associated genes were differentially regulated in IRBP KO retinas with distinct temporal variation (upregulated at P5, decreased at P40, and no change at P213 relative to WT). C1qa, Gjd2, Sntb1, and Vsx2 emerged as top genetic candidate pathways. Compared with WT, immunoblotting analysis of C1qa showed no significant differences at P5 but significantly increased protein levels at P7 in IRBP KOs. Vsx2 remained unaltered at P5 and P7 in KO when compared with WT.

Conclusions: Data analysis indicated significant contributions from C1q, Gjd2, Sntb1, and Vsx2 genes in IRBP deficiency.

目的:近视是一种复杂的疾病,其病因涉及多种遗传和环境因素的相互作用。光感受器视黄素结合蛋白(IRBP)存在于视网膜下空间,在视觉周期中起着关键作用。为了了解近视和视网膜变性,人们建立了光感受器视黄素结合蛋白基因敲除小鼠(IRBP KO)模型系统。本研究调查了 IRBP KO 中与近视、视网膜稳态和炎症相关的基因:方法:使用 Bio-Rad 自动液滴发生器和 QX200 阅读器对先天性 IRBP KO 小鼠和野生型 C57BL/6J (WT) 小鼠出生后第 5 天(P5)、P40 和 P213 天的视网膜 RNA 进行数字液滴 PCR(ddPCR)检测。目标基因的选择基于全基因组关联研究、动物模型、近视研究以及其他与视网膜稳态和炎症相关的基因。HPRT是一种看家基因,用于归一化。计算平均表达比(目标/HPRT)和标准偏差(SD)。方差分析评估统计学意义,并得出 p 结果:ddPCR 数据分析表明,在 IRBP KO 视网膜中,许多近视和炎症相关基因受到不同程度的调控,且具有明显的时间变化(相对于 WT,P5 时上调,P40 时下降,P213 时无变化)。C1qa、Gjd2、Sntb1和Vsx2成为最主要的遗传候选通路。与 WT 相比,C1qa 的免疫印迹分析表明,IRBP KOs 的蛋白水平在 P5 没有显著差异,但在 P7 显著增加。与 WT 相比,KO 的 Vsx2 在 P5 和 P7 阶段没有变化:数据分析表明,C1q、Gjd2、Sntb1和Vsx2基因在IRBP缺乏症中起着重要作用。
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引用次数: 0
Development of Microcystoid Macular Degeneration in the Retina of Nonhuman Primates: Time-Course and Associated Pathologies. 非人灵长类动物视网膜微囊藻黄斑变性的发展:非人灵长类视网膜微囊藻黄斑变性的发展:时间进程和相关病理。
IF 2 4区 医学 Q3 OPHTHALMOLOGY Pub Date : 2024-09-18 DOI: 10.1080/02713683.2024.2397028
Thomas C M Lavery,Carol A Rasmussen,Alexander W Katz,Charlene B Y Kim,James N Ver Hoeve,Paul E Miller,Peter J Sonnentag,Brian J Christian,Christopher J Murphy,David R Piwnica-Worms,Seth T Gammon,Xudong Qiu,Paul L Kaufman,T Michael Nork
PURPOSEMicrocystoid macular degeneration (MMD) is a condition where cystoid vacuoles develop within the inner nuclear layer of the retina in humans in a variety of disorders. Here we report the occurrence of MMD in non-human primates (NHPs) with various retinal ganglion cell (RGC) pathologies and evaluate the hypothesis that MMD does not precede RGC loss but follows it.METHODSMorphological studies were performed of the retinas of NHPs, specifically both rhesus (Macaca mulatta) and cynomolgus macaques (Macaca fascicularis), in which MMD was identified after induction of experimental glaucoma (EG), hemiretinal endodiathermy axotomy (HEA), and spontaneous idiopathic bilateral optic atrophy. In vivo imaging analyses included fundus photography, fluorescein angiography (FA), optical coherence tomography (OCT), adaptive optics scanning laser ophthalmoscopy (AOSLO), light microscopy, and electron microscopy.RESULTSMMD, like that seen on OCT scans of humans, was found in both rhesus and cynomolgus macaques with EG. Of 13 cynomolgus macaques with chronic EG imaged once with OCT six of 13 animals were noted to have MMD. MMD was also evident in a cynomolgus macaque with bilateral optic atrophy. Following HEA, MMD did not develop until at least 2 weeks following the RNFL loss.CONCLUSIONThese data suggest that MMD may be caused by a retrograde trans-synaptic process related to RGC loss. MMD is not associated with inflammation, nor would it be an independent indicator of drug toxicity per se in pre-clinical regulatory studies. Because of its inconsistent appearance and late development, MMD has limited use as a clinical biomarker.
目的微囊样黄斑变性(MMD)是一种在人类视网膜内核层中出现囊状空泡的病症,可导致多种疾病。在此,我们报告了在患有各种视网膜神经节细胞(RGC)病变的非人灵长类动物(NHPs)中发生的微囊样黄斑变性,并评估了微囊样黄斑变性并非发生在RGC缺失之前,而是发生在RGC缺失之后的假说。方法对NHPs(特别是恒河猴(Macaca mulatta)和猕猴(Macaca fascicularis))的视网膜进行形态学研究,在诱导实验性青光眼(EG)、半视网膜内电切术(HEA)和自发性特发性双侧视神经萎缩后,发现了MMD。体内成像分析包括眼底照相、荧光素血管造影(FA)、光学相干断层扫描(OCT)、自适应光学扫描激光眼镜(AOSLO)、光学显微镜和电子显微镜。对 13 只患有慢性 EG 的猕猴进行了一次 OCT 扫描,发现其中 6 只患有 MMD。一只患有双侧视神经萎缩的猕猴也出现了明显的MMD。这些数据表明,MMD 可能是由与 RGC 缺失有关的逆行跨突触过程引起的。MMD与炎症无关,在临床前监管研究中,它本身也不是药物毒性的独立指标。由于 MMD 的出现并不一致,而且发展较晚,因此其作为临床生物标志物的用途有限。
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引用次数: 0
Longitudinal Analysis of Tear Cytokine Ratios in Association with Dry Eye Signs and Symptoms in the Dry Eye Assessment and Management (DREAM) Study. 干眼症评估与管理 (DREAM) 研究中泪液细胞因子比率与干眼症体征和症状的纵向分析。
IF 1.7 4区 医学 Q3 OPHTHALMOLOGY Pub Date : 2024-09-12 DOI: 10.1080/02713683.2024.2398113
Cindy S Zhao, Yineng Chen, Yinxi Yu, Gui-Shuang Ying, Penny A Asbell

Purpose: To extend cross-sectional data on cytokine ratios (CRs) in dry eye disease (DED) signs by investigating longitudinal change in pro- to anti-inflammatory CRs and associations with change in DED signs and symptoms.

Methods: Secondary analysis of fifty-four subjects [mean age 57.3 (SD 13.2) years, 85.2% female; 68.5% white] with ≥ 4 uL pooled tear volumes at months 0, 6, and 12. Pro-inflammatory (IL-1b, IL-6, IL-8, IL-17A, IFN-g, and TNF-a) to anti-inflammatory (IL-6, IL-10) cytokine ratios (CR) were calculated. DED signs (corneal and conjunctival staining scores, tear break-up time, Schirmer test, Meibomian gland plugging, tear osmolarity, composite sign severity score) and symptoms [Ocular Surface Disease Index (OSDI)] were measured. Changes over time in DED signs, symptoms, and CRs were evaluated using longitudinal models. Correlations between changes in CR and changes in DED signs and symptoms were evaluated using Spearman correlation coefficients (rho).

Results: DED signs which improved over time (p < 0.001) included corneal and conjunctival staining score, tear break-up time, tear osmolarity, and composite sign severity score. Using IL-10 as anti-inflammatory, changes in corneal and conjunctival staining and composite severity score significantly correlated with changes in pro- to anti-inflammatory CRs from month 0 to 6 (|rho|: 0.29-0.45, p: 0.003-0.04) but not between month 0 to 12 (|rho|: 0.01 to 0.24, all p > 0.08). DED symptoms decreased across one year (p < = 0.001) for all OSDI measures; these changes did not correlate with changes in CRs (|rho|: 0.00 to 0.29, all p > 0.04).

Conclusions: Improvement in some DED signs across one year correlated weakly with decreases in pro- to anti-inflammatory CRs, in alignment with the understanding of DED as inflammatory. CRs may provide greater insight than absolute tear cytokine concentrations as possible DED biomarkers. Additional studies that provide standardized clinical information and tear collection and analysis are needed to validate CRs in DED.

目的:通过研究促炎症细胞因子比率(CRs)到抗炎症细胞因子比率(CRs)的纵向变化以及与干眼症(DED)体征和症状变化的关联,扩展干眼症(DED)体征中细胞因子比率(CRs)的横断面数据:对 54 名受试者(平均年龄 57.3(SD 13.2)岁,85.2% 为女性;68.5% 为白人)在第 0、6 和 12 个月的泪液总量≥ 4 uL 的情况进行二次分析。计算促炎细胞因子(IL-1b、IL-6、IL-8、IL-17A、IFN-g 和 TNF-a)与抗炎细胞因子(IL-6、IL-10)之比 (CR)。对DED体征(角膜和结膜染色评分、泪液破裂时间、Schirmer试验、睑板腺堵塞、泪液渗透压、综合体征严重程度评分)和症状[眼表疾病指数(OSDI)]进行了测量。采用纵向模型对 DED 体征、症状和 CR 随时间的变化进行评估。使用斯皮尔曼相关系数(rho)评估 CR 变化与 DED 体征和症状变化之间的相关性:结果:随着时间的推移,DED体征有所改善(p p:0.003-0.04),但在第0个月至第12个月期间没有改善(|rho|:0.01-0.24,所有p > 0.08)。DED症状在一年内有所减轻(P P > 0.04):结论:DED某些体征在一年内的改善与促炎至抗炎CRs的下降呈弱相关性,这与DED是炎症性的认识一致。作为可能的 DED 生物标志物,泪液细胞因子浓度可能比泪液细胞因子绝对浓度更能说明问题。要验证 DED 中的 CRs,还需要更多提供标准化临床信息、泪液采集和分析的研究。
{"title":"Longitudinal Analysis of Tear Cytokine Ratios in Association with Dry Eye Signs and Symptoms in the Dry Eye Assessment and Management (DREAM) Study.","authors":"Cindy S Zhao, Yineng Chen, Yinxi Yu, Gui-Shuang Ying, Penny A Asbell","doi":"10.1080/02713683.2024.2398113","DOIUrl":"https://doi.org/10.1080/02713683.2024.2398113","url":null,"abstract":"<p><strong>Purpose: </strong>To extend cross-sectional data on cytokine ratios (CRs) in dry eye disease (DED) signs by investigating longitudinal change in pro- to anti-inflammatory CRs and associations with change in DED signs and symptoms.</p><p><strong>Methods: </strong>Secondary analysis of fifty-four subjects [mean age 57.3 (SD 13.2) years, 85.2% female; 68.5% white] with ≥ 4 uL pooled tear volumes at months 0, 6, and 12. Pro-inflammatory (IL-1b, IL-6, IL-8, IL-17A, IFN-g, and TNF-a) to anti-inflammatory (IL-6, IL-10) cytokine ratios (CR) were calculated. DED signs (corneal and conjunctival staining scores, tear break-up time, Schirmer test, Meibomian gland plugging, tear osmolarity, composite sign severity score) and symptoms [Ocular Surface Disease Index (OSDI)] were measured. Changes over time in DED signs, symptoms, and CRs were evaluated using longitudinal models. Correlations between changes in CR and changes in DED signs and symptoms were evaluated using Spearman correlation coefficients (rho).</p><p><strong>Results: </strong>DED signs which improved over time (<i>p</i> < 0.001) included corneal and conjunctival staining score, tear break-up time, tear osmolarity, and composite sign severity score. Using IL-10 as anti-inflammatory, changes in corneal and conjunctival staining and composite severity score significantly correlated with changes in pro- to anti-inflammatory CRs from month 0 to 6 (|rho|: 0.29-0.45, <i>p</i>: 0.003-0.04) but not between month 0 to 12 (|rho|: 0.01 to 0.24, all <i>p</i> > 0.08). DED symptoms decreased across one year (<i>p</i> < = 0.001) for all OSDI measures; these changes did not correlate with changes in CRs (|rho|: 0.00 to 0.29, all <i>p</i> > 0.04).</p><p><strong>Conclusions: </strong>Improvement in some DED signs across one year correlated weakly with decreases in pro- to anti-inflammatory CRs, in alignment with the understanding of DED as inflammatory. CRs may provide greater insight than absolute tear cytokine concentrations as possible DED biomarkers. Additional studies that provide standardized clinical information and tear collection and analysis are needed to validate CRs in DED.</p>","PeriodicalId":10782,"journal":{"name":"Current Eye Research","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142281642","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
Revolutionizing Ophthalmic Care: A Review of Ocular Hydrogels from Pathologies to Therapeutic Applications. 革新眼科护理:从病理到治疗应用的眼部水凝胶回顾。
IF 2 4区 医学 Q3 OPHTHALMOLOGY Pub Date : 2024-09-11 DOI: 10.1080/02713683.2024.2396385
Pankaj Pal,Sharda Sambhakar,Shailendra Paliwal
PURPOSEThis comprehensive review is designed to elucidate the transformative role and multifaceted applications of ocular hydrogels in contemporary ophthalmic therapeutic strategies, with a particular emphasis on their capability to revolutionize drug delivery mechanisms and optimize patient outcomes.METHODSA systematic and structured methodology is employed, initiating with a succinct exploration of prevalent ocular pathologies and delineating the corresponding therapeutic agents. This serves as a precursor for an extensive examination of the diverse methodologies and fabrication techniques integral to the design, development, and application of hydrogels specifically tailored for ophthalmic pharmaceutical delivery. The review further scrutinizes the pivotal manufacturing processes that significantly influence hydrogel efficacy and delves into an analysis of the current spectrum of hydrogel-centric ocular formulations.RESULTSThe review yields illuminating insights into the escalating prominence of ocular hydrogels within the medical community, substantiated by a plethora of ongoing clinical investigations. It reveals the dynamic and perpetually evolving nature of hydrogel research and underscores the extensive applicability and intricate progression of transposing biologics-loaded hydrogels from theoretical frameworks to practical clinical applications.CONCLUSIONSThis review accentuates the immense potential and promising future of ocular hydrogels in the realm of ophthalmic care. It not only serves as a comprehensive guide but also as a catalyst for recognizing the transformative potential of hydrogels in augmenting drug delivery mechanisms and enhancing patient outcomes. Furthermore, it draws attention to the inherent challenges and considerations that necessitate careful navigation by researchers and clinicians in this progressive field.
目的本综述旨在阐明眼部水凝胶在当代眼科治疗策略中的变革性作用和多方面应用,特别强调水凝胶在革新给药机制和优化患者疗效方面的能力。方法本综述采用了系统化和结构化的方法,首先对眼部常见病症进行了简要探讨,并对相应的治疗药物进行了划分。在此基础上,对设计、开发和应用专门用于眼科给药的水凝胶所不可或缺的各种方法和制造技术进行了广泛的研究。本综述进一步仔细研究了对水凝胶疗效有重大影响的关键生产工艺,并深入分析了当前以水凝胶为中心的眼科配方。结果本综述深入揭示了眼科水凝胶在医学界日益突出的地位,大量正在进行的临床研究也证实了这一点。综述揭示了水凝胶研究的动态和不断发展的本质,并强调了生物载荷水凝胶从理论框架到实际临床应用的广泛适用性和错综复杂的发展过程。它不仅是一本全面的指南,还能促进人们认识到水凝胶在增强给药机制和提高患者疗效方面的变革潜力。此外,它还提请人们注意固有的挑战和注意事项,这些挑战和注意事项需要研究人员和临床医生在这一不断进步的领域中小心驾驭。
{"title":"Revolutionizing Ophthalmic Care: A Review of Ocular Hydrogels from Pathologies to Therapeutic Applications.","authors":"Pankaj Pal,Sharda Sambhakar,Shailendra Paliwal","doi":"10.1080/02713683.2024.2396385","DOIUrl":"https://doi.org/10.1080/02713683.2024.2396385","url":null,"abstract":"PURPOSEThis comprehensive review is designed to elucidate the transformative role and multifaceted applications of ocular hydrogels in contemporary ophthalmic therapeutic strategies, with a particular emphasis on their capability to revolutionize drug delivery mechanisms and optimize patient outcomes.METHODSA systematic and structured methodology is employed, initiating with a succinct exploration of prevalent ocular pathologies and delineating the corresponding therapeutic agents. This serves as a precursor for an extensive examination of the diverse methodologies and fabrication techniques integral to the design, development, and application of hydrogels specifically tailored for ophthalmic pharmaceutical delivery. The review further scrutinizes the pivotal manufacturing processes that significantly influence hydrogel efficacy and delves into an analysis of the current spectrum of hydrogel-centric ocular formulations.RESULTSThe review yields illuminating insights into the escalating prominence of ocular hydrogels within the medical community, substantiated by a plethora of ongoing clinical investigations. It reveals the dynamic and perpetually evolving nature of hydrogel research and underscores the extensive applicability and intricate progression of transposing biologics-loaded hydrogels from theoretical frameworks to practical clinical applications.CONCLUSIONSThis review accentuates the immense potential and promising future of ocular hydrogels in the realm of ophthalmic care. It not only serves as a comprehensive guide but also as a catalyst for recognizing the transformative potential of hydrogels in augmenting drug delivery mechanisms and enhancing patient outcomes. Furthermore, it draws attention to the inherent challenges and considerations that necessitate careful navigation by researchers and clinicians in this progressive field.","PeriodicalId":10782,"journal":{"name":"Current Eye Research","volume":null,"pages":null},"PeriodicalIF":2.0,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142180290","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}
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Current Eye Research
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