Ocular Surface最新文献_第7页

Janus kinase inhibitors in the treatment of refractory cicatrizing conjunctivitis in pemphigoid Janus激酶抑制剂治疗类天疱疮难治性结膜炎。

IF 5.9 1区医学 Q1 OPHTHALMOLOGY

Ocular Surface

Pub Date : 2025-05-12 DOI: 10.1016/j.jtos.2025.05.002

Celine Nguyen , Ebuka Eziama , Arturo R. Dominguez , Jennifer H. Cao

Objective

To evaluate the efficacy of Janus kinase inhibitor (JAKi) therapy in managing cicatrizing conjunctivitis associated with ocular cicatricial pemphigoid (OCP) and mucous membrane pemphigoid with ocular involvement (ocMMP).

Methods

Retrospective chart review of patients with cicatrizing conjunctivitis secondary to OCP or ocMMP who underwent treatment with JAKi at a tertiary academic medical center from August 2015 to November 2024 for minimum follow-up of six months. Collected data included demographics, Foster stage of cicatrization, and treatment course.

Results

Thirty-two patients met inclusion criteria: 23 (71.9 %) with OCP and 9 (28.1 %) with ocMMP. 96.9 % of patients demonstrated clinical improvement within twelve months of treatment initiation. Best response achieved were as follows: 1 (3.1 %) no response, 17 (53.1 %) partial response, 14 (43.8 %) complete remission, and 12 (37.5 %) steroid-free complete remission. The mean time to partial response, complete remission, steroid-free complete remission was 3.1 ± 1.8 (range, 0.9–8.3), 7.8 ± 3.3 months (range, 2.3–14.7 months), and 10.3 ± 7.4 months, (range, 2.3–31.4 months), respectively. Relapse in disease activity occurred in 8/32 (25.0 %) of patients. Side effects occurred in 8/32 (25.0 %) of patients. Four patients (12.5 %) discontinued therapy due to severe adverse events, including transient ischemic attack, pulmonary embolism, pyelonephritis, and cholecystitis. There was a significant association between lower Foster cicatrization stages and achieving remission (U = 630.0, p = 0.0036), with a rank-biserial correlation of 0.72.

Conclusions

JAK inhibitor therapy demonstrates efficacy in the management of recalcitrant cicatrizing conjunctivitis associated with pemphigoid. These findings highlight JAK inhibitors as a promising therapeutic option for refractory cases.

目的：评价Janus激酶抑制剂（JAKinib）治疗瘢痕性结膜炎伴眼瘢痕性类天疱疮（OCP）和黏膜类天疱疮伴眼累及（ocMMP）的疗效。方法：回顾性分析2015年8月至2024年11月在某三级学术医疗中心接受JAKinibs治疗的OCP或ocMMP继发瘢痕性结膜炎患者，随访时间至少为6个月。收集的数据包括人口统计学、愈合培养阶段和疗程。结果：32例患者符合纳入标准：OCP 23例（71.9%），ocMMP 9例（28.1%）。96.9%的患者在开始治疗的12个月内表现出临床改善。获得的最佳缓解如下：1例（3.1%）无缓解，17例（53.1%）部分缓解，14例（43.8%）完全临床缓解，12例（37.5%）无类固醇缓解。达到部分缓解、完全临床缓解和无类固醇缓解的平均时间分别为3.1±1.8个月（范围0.9-8.3）、7.8±3.3个月（范围2.3-14.7个月）和10.3±7.4个月（范围2.3-31.4个月）。8/32（25.0%）患者出现疾病活动复发。32例患者中有8例（25.0%）出现不良反应。4例患者（12.5%）因严重不良事件停止治疗，包括短暂性脑缺血发作、肺栓塞、肾盂肾炎和胆囊炎。较低的福斯特愈合阶段与获得缓解之间存在显著相关（U = 630.0, p = 0.0036），秩双列相关系数为0.72。结论：JAK抑制剂治疗与类天疱疮相关的顽固性结膜炎有效。这些发现突出了JAK抑制剂作为难治性病例的一种有希望的治疗选择。

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引用次数: 0

Ranking the efficacy of topical treatments for ocular allergy: A network meta-analysis of current evidence 眼过敏局部治疗的疗效排名：当前证据的网络荟萃分析

IF 5.9 1区医学 Q1 OPHTHALMOLOGY

Ocular Surface

Pub Date : 2025-05-08 DOI: 10.1016/j.jtos.2025.05.003

Luksanaporn Krungkraipetch , Taweelarp Tansavadi , Dechathorn Krungkraipetch

Purpose

To evaluate and rank the comparative effectiveness of topical treatments for different types of ocular allergies through a systematic review and network meta-analysis.

Methods

A systematic search of electronic databases identified between January 2000 and December 2024 from PubMed, Cochrane CENTRAL, Google Scholar, and Scopus databases. Study Selection; randomized controlled trials assessing topical treatments for ocular allergy, including antihistamines, corticosteroids, immunomodulators, and combination therapies. Data Extraction and Synthesis; data were independently extracted and analyzed following PRISMA guidelines. Direct and indirect comparisons were evaluated using network meta-analysis, and SUCRA rankings assessed relative efficacy. Main Outcomes and Measures; reduction in ocular itching, redness, and inflammation. PROSPERO Registration number: CRD42025634572.

Results

Olopatadine 0.1 % demonstrated highest efficacy in seasonal and perennial allergic conjunctivitis (SUCRA 0.88 and 0.85, respectively), while Tacrolimus 0.1 % showed superior effectiveness in vernal and atopic keratoconjunctivitis (SUCRA 0.92 and 0.89, respectively). Overall treatment effect was significant (OR = 6.95, 95 % CI: 6.24–7.75) with moderate heterogeneity (I² = 50.8 %). Subgroup analysis revealed consistent efficacy across different types of allergic conjunctivitis, with seasonal allergic conjunctivitis showing the highest cumulative ranking probability (89.0 %).

Conclusions

This network meta-analysis provides strong evidence supporting condition-specific treatment approaches in ocular allergies. Newer antihistamines, particularly Olopatadine, are most effective for mild-moderate conditions, while immunomodulators, especially Tacrolimus, show superior efficacy in severe cases. These findings provide clear evidence-based hierarchies for clinical decision-making in the management of different types of allergic conjunctivitis.

目的通过系统综述和网络荟萃分析，对不同类型眼部过敏的局部治疗效果进行评价和排序。方法系统检索2000年1月至2024年12月PubMed、Cochrane CENTRAL、谷歌Scholar和Scopus数据库中的电子数据库。研究选择;随机对照试验评估眼部过敏的局部治疗，包括抗组胺药、皮质类固醇、免疫调节剂和联合治疗。数据提取与综合；数据按照PRISMA指南独立提取和分析。使用网络荟萃分析评估直接和间接比较，SUCRA排名评估相对疗效。主要成果和措施；减轻眼部瘙痒、红肿和炎症。普洛斯彼罗注册号：CRD42025634572。结果0.1%索洛他定对季节性和常年性变应性结膜炎的疗效最高（SUCRA分别为0.88和0.85），0.1%他克莫司对春季性和特应性角膜结膜炎的疗效最高（SUCRA分别为0.92和0.89）。总体治疗效果显著（OR = 6.95, 95% CI: 6.24-7.75），异质性中等（I2 = 50.8%）。亚组分析显示，不同类型变应性结膜炎的疗效一致，季节性变应性结膜炎的累积排名概率最高（89.0%）。结论：该网络荟萃分析为眼部过敏的特异性治疗方法提供了强有力的证据。较新的抗组胺药，特别是奥洛帕他定，对轻中度疾病最有效，而免疫调节剂，特别是他克莫司，在严重病例中表现出更好的疗效。这些发现为不同类型过敏性结膜炎的临床决策提供了明确的循证分级。

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引用次数: 0

The ocular surface tear film as a biomarker for systemic health 眼表泪膜作为系统健康的生物标志物

IF 5.9 1区医学 Q1 OPHTHALMOLOGY

Ocular Surface

Pub Date : 2025-05-08 DOI: 10.1016/j.jtos.2025.05.005

Navid Fotovat-Ahmadi , Omer Siddiqui , Joshua Ong , Chanon Thanitcul , Christian Reinhardt , Stephanie M. Cologna , Vinay Kumar Aakalu

The tear film is a complex structure with rich interactions with the human body. A growing body of evidence suggests that measuring changes in protein, lipid, or other metabolite concentration in the tear film can be used to help detect disease. Particularly in the era of precision medicine, the tear film serves as a promising source of non-invasive insights into systemic health for early diagnosis and treatment. This paper analyzes the latest research in tear film biomarkers for systemic diseases. The review was conducted through PubMed and Embase databases using the PRISMA protocol and includes 54 articles. This paper first reviews the anatomy and physiology of tear film, as well as the latest proteomic analysis techniques on the tear film. We then provide a disease-by-disease review on the tear film as a biomarker including 5 articles related to Alzheimer's Disease, 10 articles related to Cancers, 1 article related to Cystic Fibrosis, 1 article related to Migraines, 4 articles related to Multiple Sclerosis, 15 articles related to Parkinson's Disease, 7 articles related to Rheumatoid Arthritis, and 11 articles related to Thyroid Disease. This paper highlights the promising results of these studies yet also reviews the challenges with limited sample sizes, reproducibility, and biological understanding of biomarkers. We conclude this paper with insights for future work to ensure clinical validity and generalizability. Ultimately, the tear film is a clinically accessible, complex structure that provides a wealth of information that may contribute to a more comprehensive understanding of systemic health.

泪膜是一种复杂的结构，与人体有着丰富的相互作用。越来越多的证据表明，测量泪膜中蛋白质、脂质或其他代谢物浓度的变化可用于帮助检测疾病。特别是在精准医疗的时代，泪膜作为一种有希望的非侵入性洞察系统健康的早期诊断和治疗的来源。本文分析了泪膜生物标志物在全身性疾病中的最新研究进展。该综述使用PRISMA协议通过PubMed和Embase数据库进行，包括54篇文章。本文首先综述了泪膜的解剖学和生理学，以及最新的泪膜蛋白质组学分析技术。然后，我们对泪膜作为生物标志物的疾病进行逐一回顾，包括5篇与阿尔茨海默病相关的文章，10篇与癌症相关的文章，1篇与囊性纤维化相关的文章，1篇与偏头痛相关的文章，4篇与多发性硬化症相关的文章，15篇与帕金森病相关的文章，7篇与类风湿性关节炎相关的文章，以及11篇与甲状腺疾病相关的文章。本文强调了这些研究的有希望的结果，但也回顾了有限的样本量，可重复性和生物标志物的生物学理解的挑战。我们总结了对未来工作的见解，以确保临床有效性和普遍性。最终，泪膜是一种临床上可接近的复杂结构，它提供了丰富的信息，可能有助于更全面地了解全身健康。

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引用次数: 0

Retinoic acid promotes conjunctival epithelium differentiation and goblet cell regeneration: evidence from novel 3D conjunctival organoids and whole-mount PAS staining 维甲酸促进结膜上皮分化和杯状细胞再生：来自新型三维结膜类器官和全载PAS染色的证据

IF 5.9 1区医学 Q1 OPHTHALMOLOGY

Ocular Surface

Pub Date : 2025-05-08 DOI: 10.1016/j.jtos.2025.05.006

Ruize Shi , Mengyi Jin , Janbo Jin , Lina Xu , Zeyu Liu , Lan Zheng , Baihui Zeng , Kerui Wang , Xiang Li , Shurong Wang , Cheng Li

Purpose

To investigate the differentiation effects of retinoic acid on primary conjunctival epithelium using both 2D and 3D models, and to evaluate its in vivo effects on conjunctival epithelium and goblet cells in mice using a novel goblet cell assessment method.

Methods

The differentiation effects of retinoic acid were evaluated in vitro using 2D culture and 3D organoid models. Under 2D conditions, differentiation was assessed using qRT-PCR, light microscopy, immunofluorescence staining, and Western blot analysis for goblet cell markers. In the 3D organoid model, differentiation was confirmed using qRT-PCR, immunofluorescence staining, and AB-PAS staining. In vivo, a novel goblet cell assessment method—whole-mount PAS staining—was introduced, along with H&E staining to evaluate the effects of retinoic acid eye drops.

Results

In the 2D culture model, retinoic acid induced cell fusion, decreased stemness marker expression, and increased goblet cell differentiation markers. In the 3D organoid model, retinoic acid treatment led to elevated expression of goblet cell markers, including Muc5ac, Tff1, and Gcnt3, as confirmed by qRT-PCR, AB-PAS staining, and immunofluorescence. In vivo, retinoic acid eye drops promoted goblet cell generation, as demonstrated by the novel assessment method.

Conclusions

Retinoic acid promotes conjunctival epithelial differentiation and goblet cell regeneration both in vitro and in vivo. A novel method for goblet cell detection is proposed, providing a more accurate and reliable approach for evaluating conjunctival goblet cells in future research.

目的采用二维和三维模型研究维甲酸对小鼠原代结膜上皮细胞的分化作用，并采用一种新的杯状细胞评价方法，评价维甲酸对小鼠结膜上皮细胞和杯状细胞的体内影响。方法采用体外二维培养和三维类器官模型评价维甲酸的体外分化作用。在二维条件下，使用qRT-PCR、光镜、免疫荧光染色和杯状细胞标记物的Western blot分析来评估分化。在三维类器官模型中，采用qRT-PCR、免疫荧光染色和AB-PAS染色证实分化。在体内，引入了一种新的杯状细胞评估方法-全载PAS染色，以及H&；E染色来评估视黄酸滴眼液的效果。结果在二维培养模型中，维甲酸诱导细胞融合，降低干性标志物表达，增加杯状细胞分化标志物表达。在3D类器官模型中，经qRT-PCR、AB-PAS染色和免疫荧光证实，维甲酸处理导致杯状细胞标记物Muc5ac、Tff1和Gcnt3的表达升高。在体内，维甲酸滴眼液促进杯状细胞的生成，这一新的评估方法证实了这一点。结论维甲酸对体外和体内结膜上皮细胞分化和杯状细胞再生均有促进作用。提出了一种新的杯状细胞检测方法，为今后结膜杯状细胞的检测提供了一种更准确、更可靠的方法。

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引用次数: 0

Identification of a translatable animal model for dry eye disease using comparative analysis of tear proteins across species 利用跨物种泪液蛋白的比较分析鉴定可翻译的干眼病动物模型

IF 5.9 1区医学 Q1 OPHTHALMOLOGY

Ocular Surface

Pub Date : 2025-05-07 DOI: 10.1016/j.jtos.2025.05.004

Mayelín Pérez-Perdomo , Ana González-López , Laura Ortega-Llamas , David Alba-Molina , Mario Blanco-Blanco , María del Mar Granados , Adrián Guerrero-Moreno , Stephen Carl Pflugfelder , Christoph Ullmer , Sascha Fauser , Yolanda Jiménez-Gómez , Miguel González-Andrades

Purpose

This study aimed to assess the similarity of tear proteins between experimental animals and humans to identify the most translational animal model for dry eye disease (DED).

Methods

Eleven species were selected for a structural and physicochemical comparison of healthy human tear fluid proteins involved in DED. Amino acid sequences were compared using BLAST. Protein primary structure, isoelectric point (pI) and grand average of hydropathicity (GRAVY) were determined using ExPASy and compared with humans.

Results

Among non-primate mammals, the cat (69.7 %) and pig (68.7 %) showed the highest protein sequence similarity to humans. The ruminants and cat showed amino acid content changes for the highest number of proteins (≥3/15). The pig, rabbit, dog and rodents had the closest global pI values to humans, while the cat showed the highest protein number (9/15) with pI values far from humans. GRAVY values for the pig and dog were the closest to humans. Tear-soluble factor study revealed that the pig was the only species with high similarity for all proteins (>60 %). Amino acid content was similar for most species compared to humans, except mouse for IL-6 and rodents and pig for IL-8. The pI and GRAVY values varied across species, though the pig and sheep were the only ones with similar pI to humans for four out of five factors.

Conclusion

The pig exhibited the highest similarity to humans in tear protein analysis among non-primate mammals, suggesting that the porcine model may be the most translational for DED research.

目的本研究旨在评估实验动物和人类泪液蛋白的相似性，以确定干眼病（DED）最具可转译性的动物模型。方法选取6种正常人泪液中与DED相关的蛋白进行结构和理化比较。利用BLAST对氨基酸序列进行比较。用ExPASy测定蛋白一级结构、等电点（pI）和亲水性大平均值（GRAVY），并与人作比较。结果在非灵长类动物中，猫（69.7%）和猪（68.7%）与人类的蛋白质序列相似性最高。反刍动物和猫的氨基酸含量变化最大，蛋白质含量≥3/15。猪、兔、狗和啮齿动物的pI值与人类最接近，而猫的pI值最高（9/15），与人类的pI值相差甚远。猪和狗的肉汁值最接近人类。泪溶因子研究表明，猪是唯一一种在所有蛋白质上具有高度相似性的物种（60%）。除了小鼠的IL-6、啮齿动物和猪的IL-8外，大多数物种的氨基酸含量与人类相似。不同物种的pI和GRAVY值各不相同，尽管猪和羊是仅有的在5个因素中有4个与人类相似的pI。结论在非灵长类哺乳动物中，猪与人在泪液蛋白分析上的相似性最高，表明猪模型可能是最适合用于DED研究的模型。

{"title":"Identification of a translatable animal model for dry eye disease using comparative analysis of tear proteins across species","authors":"Mayelín Pérez-Perdomo , Ana González-López , Laura Ortega-Llamas , David Alba-Molina , Mario Blanco-Blanco , María del Mar Granados , Adrián Guerrero-Moreno , Stephen Carl Pflugfelder , Christoph Ullmer , Sascha Fauser , Yolanda Jiménez-Gómez , Miguel González-Andrades","doi":"10.1016/j.jtos.2025.05.004","DOIUrl":"10.1016/j.jtos.2025.05.004","url":null,"abstract":"<div><h3>Purpose</h3><div>This study aimed to assess the similarity of tear proteins between experimental animals and humans to identify the most translational animal model for dry eye disease (DED).</div></div><div><h3>Methods</h3><div>Eleven species were selected for a structural and physicochemical comparison of healthy human tear fluid proteins involved in DED. Amino acid sequences were compared using BLAST. Protein primary structure, isoelectric point (pI) and grand average of hydropathicity (GRAVY) were determined using ExPASy and compared with humans.</div></div><div><h3>Results</h3><div>Among non-primate mammals, the cat (69.7 %) and pig (68.7 %) showed the highest protein sequence similarity to humans. The ruminants and cat showed amino acid content changes for the highest number of proteins (≥3/15). The pig, rabbit, dog and rodents had the closest global pI values to humans, while the cat showed the highest protein number (9/15) with pI values far from humans. GRAVY values for the pig and dog were the closest to humans. Tear-soluble factor study revealed that the pig was the only species with high similarity for all proteins (>60 %). Amino acid content was similar for most species compared to humans, except mouse for IL-6 and rodents and pig for IL-8. The pI and GRAVY values varied across species, though the pig and sheep were the only ones with similar pI to humans for four out of five factors.</div></div><div><h3>Conclusion</h3><div>The pig exhibited the highest similarity to humans in tear protein analysis among non-primate mammals, suggesting that the porcine model may be the most translational for DED research.</div></div>","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":"37 ","pages":"Pages 260-272"},"PeriodicalIF":5.9,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143931377","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Use of a transgenic mouse model for in vivo monitoring of corneal pathologies following Sulfur Mustard Exposure 利用转基因小鼠模型在体内监测硫芥暴露后角膜病变

IF 5.9 1区医学 Q1 OPHTHALMOLOGY

Ocular Surface

Pub Date : 2025-04-24 DOI: 10.1016/j.jtos.2025.04.007

Ariel Gore, Rahav Efrati, Shelly Atanelov, Pnina Glick, Maayan Cohen, Hila Gutman, Relli Gez, Vered Horwitz

Purpose

The dynamic course of sulfur mustard (SM)-induced ocular insult involves an acute phase, which may progress to a chronic phase or a quiescent period, followed by late pathology. Visualizing pathological corneal changes in vivo could enhance understanding of this process and aid treatment development.

Methods

SM burn was induced in the right eyes of three transgenic mouse strains—expressing RFP under the VE-Cadherin promoter (blood vessels and hematopoietic cells), GFP under the keratin 15 promoter (limbal stem cells), and YFP under the Thy-1 promoter (mid-stromal nerve fibers, MSNFs)—by vapor exposure. Cell infiltration, neovascularization (NV), innervation loss, and stem cell (SC) depletion were monitored in vivo by stereomicroscopy for up to 8 weeks. Corneal whole-mounts were used to assess 360° structures, infiltrating cells, and subbasal nerve plexus (SNP) loss. Histology included H&E, Masson-Trichrome, and periodic acid-Schiff staining.

Results

A 35-s exposure caused minor ocular insult with moderate SNP changes, corneal cell infiltration, and reversible SC loss, mostly resolving by 4 weeks. A 120-s exposure caused severe insult with NV, extensive MSNF and SNP loss, marked CD45⁺ and Iba1⁺ infiltration, and irreversible SC depletion. NV, stromal inflammation, edema, epithelial changes, and goblet cells were seen in histology and correlated with fluorescence imaging.

Conclusions

This study demonstrates the utility of transgenic mice as powerful models for studying SM-induced ocular injury and for developing novel therapeutic strategies.

目的硫芥（SM）致眼损伤的动态过程包括急性期，可发展为慢性期或静息期，随后是晚期病理。在体内观察角膜病理变化可以加深对这一过程的理解，并有助于治疗的发展。方法采用蒸汽暴露法，在VE-Cadherin启动子（血管和造血细胞）下表达RFP，在角蛋白15启动子（角膜干细胞）下表达GFP，在hy-1启动子（中基质神经纤维，MSNFs）下表达YFP的三种转基因小鼠右眼诱导ssm烧伤。通过体视显微镜观察细胞浸润、新生血管形成（NV）、神经支配丧失和干细胞（SC）耗竭长达8周。角膜全支架用于评估360°结构、浸润细胞和基底下神经丛（SNP）损失。组织学包括H&；E，马松-三色，周期性酸-希夫染色。结果sa - 35-s暴露引起轻度眼损伤，伴有中度SNP改变、角膜细胞浸润和可逆性SC丢失，大部分在4周内消退。暴露120 s可引起NV的严重损伤，广泛的MSNF和SNP丢失，明显的CD45+和Iba1+浸润，以及不可逆的SC消耗。组织学上可见NV、间质炎症、水肿、上皮改变和杯状细胞，并与荧光成像相关。结论转基因小鼠可作为研究sm致眼损伤的有效模型，并可用于开发新的治疗策略。

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引用次数: 0

Desiccation stress triggers and exacerbates experimental ocular Graft-versus-host-disease 干燥应激触发并加剧实验性眼移植物抗宿主病

IF 5.9 1区医学 Q1 OPHTHALMOLOGY

Ocular Surface

Pub Date : 2025-04-24 DOI: 10.1016/j.jtos.2025.04.008

Uta Gehlsen , Martina Maass , Daniela Stary , Svenja Wagener-Ryczek , Gwen Musial , Manolis Pasparakis , Cintia S. de Paiva , Michael E. Stern , Philipp Steven

Introduction

Chronic ocular graft-versus-host disease (oGVHD) is one of the most common complications after allogeneic hematopoietic stem cell transplantation (aHSCT). Recent studies indicate that desiccating stress by air-conditioning in transplantation wards increases the incidence of oGVHD. To test the hypothesis that experimental desiccating stress is a risk factor for oGVHD a mouse model of oGVHD was subjected to experimental desiccating stress.

Materials/Methods: A previously established chemo-induced minor-mismatch mouse model of oGVHD was used. One group was challenged with desiccating stress for 18 days and compared to non-desiccated GVHD animals. Clinical phenotyping was performed weekly and ocular tissue and regional lymph nodes were collected on days 7 and 28 for flow-cytometry, tear film cytokine analysis, histology for corneal lymphatics and dendritic cell counts, and corneal gene expression.

Results

Desiccating stress leads to significant earlier and more severe systemic and oGVHD accompanied by higher numbers of activated corneal dendritic cells, higher expression of TNF in tear film and earlier corneal lymphangiogenesis. Gene expression analysis suggests that systemic GVHD severity may influence oGVHD. Different inflammatory pathways are upregulated at d28 following desiccating stress in contrast to non-desiccated GVHD.

Conclusions

The data presented strengthens the hypothesis, that desiccating stress during aHSCT is a risk factor for oGVHD. Together with already published clinical data, there is increasing evidence that implicates protecting patients from desiccation during the engraftment of allogeneic hematopoietic stem cells. Furthermore, specific prophylactic therapies should be developed and tested to reduce the incidence and severity of oGVHD.

慢性眼部移植物抗宿主病（oGVHD）是同种异体造血干细胞移植（aHSCT）后最常见的并发症之一。最近的研究表明，移植病房的空调干燥压力增加了oGVHD的发病率。为了验证实验性干燥应激是oGVHD危险因素的假设，我们对oGVHD小鼠模型进行了实验性干燥应激。材料/方法：采用先前建立的化学诱导的oGVHD小鼠小错配模型。其中一组受到干燥压力18天，并与未干燥的GVHD动物进行比较。每周进行临床表型分型，于第7天和第28天采集眼部组织和区域淋巴结进行流式细胞术、泪膜细胞因子分析、角膜淋巴管组织学和树突状细胞计数以及角膜基因表达。结果干燥应激可导致系统性和oGVHD的早期和严重程度，并伴有活化的角膜树突状细胞数量增加，泪膜中TNF表达增加，角膜淋巴管生成提前。基因表达分析提示全身性GVHD严重程度可能影响oGVHD。与非干燥GVHD相比，干燥应激后28天不同的炎症通路上调。结论：上述数据强化了aHSCT期间的干燥应激是oGVHD的危险因素这一假设。加上已经发表的临床数据，越来越多的证据表明，在同种异体造血干细胞移植过程中，保护患者免受干燥。此外，应该开发和测试特定的预防性疗法，以减少oGVHD的发病率和严重程度。

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引用次数: 0

Ocular graft-versus-host disease: Experience, incidence, and treatment outcomes at a university-based tertiary care ophthalmology center 眼移植物抗宿主病：一所大学三级保健眼科中心的经验、发病率和治疗结果

IF 5.9 1区医学 Q1 OPHTHALMOLOGY

Ocular Surface

Pub Date : 2025-04-11 DOI: 10.1016/j.jtos.2025.04.006

Zeenal G. Dabre , Tanya Sheth , Elias Hernandez , Jessica Mun , Diana Hernandez , Nancy Ascencio , Christian Kim , Monazzah Sarwar , Kiera Byrne , Anubhav Pradeep , Damiano Rondelli , Christine Mun , Sandeep Jain

Objective

This study describes the clinical experience, incidence, and outcomes of treating chronic ocular graft-versus-host disease (oGVHD) at a tertiary care ophthalmology center.

Methods

This retrospective analysis included 413 post-hematopoietic stem cell transplant patients. Ocular GVHD was diagnosed using the international chronic oGVHD consensus group criteria. Based on the severity of the initial presentation and the topical treatment received accordingly, patients with definite oGVHD were divided into three groups: Group A received combination of steroids, serum tears, and pooled human immunoglobulin; Group B received steroids and serum tears; and Group C received steroids only. Treatment response was analyzed using Wilcoxon rank-sum and Kruskal-Wallis test.

Results

53 % of patients presented with definite oGVHD manifestations at the initial visit with 16 % of these patients presenting with only ocular manifestations of chronic GVHD. Among those initially categorized as none or probable oGVHD only 18 % progressed to definite oGVHD during the follow-up period. Patients in treatment group A and B showed significant reduction (p < 0.01) in corneal staining at follow-up compared to initial visit. However, corneal staining reduction in treatment group C did not achieve significance (p = 0.06). Visual analogue scale scores decreased in all groups, with treatment group A (p < 0.01), group B (p < 0.01), and group C (p = 0.014) each showing improvement in symptoms at follow-up compared to initial visit.

Conclusion

The high incidence of oGVHD in post-HSCT patients may be related to belated referral to eye care providers. Initiating combinatorial treatment that is based on the severity of oGVHD manifestations results in significant clinical improvement.

目的介绍某三级保健眼科中心治疗慢性眼部移植物抗宿主病（oGVHD）的临床经验、发病率和结果。方法对413例造血干细胞移植后患者进行回顾性分析。眼部GVHD的诊断采用国际慢性oGVHD共识组标准。根据初始表现的严重程度和相应的局部治疗，将明确的oGVHD患者分为三组：A组接受类固醇、血清泪液和混合人免疫球蛋白联合治疗；B组给予类固醇和血清泪液；C组仅接受类固醇治疗。采用Wilcoxon秩和和Kruskal-Wallis检验分析治疗反应。结果53%的患者在初次就诊时表现出明确的oGVHD表现，其中16%的患者仅表现为慢性GVHD的眼部表现。在最初被归类为无或可能oGVHD的患者中，只有18%的患者在随访期间发展为明确的oGVHD。治疗组A、B组患者表现明显降低(p <；与初次就诊相比，随访时角膜染色差异为0.01)。而C组角膜染色减少无显著性意义（p = 0.06）。各组视觉模拟量表评分均下降，A组(p <；0.01)， B组(p <；0.01)和C组（p = 0.014）在随访时均显示与初次就诊相比症状有所改善。结论移植后患者oGVHD的高发可能与转诊较晚有关。根据oGVHD表现的严重程度启动联合治疗可显著改善临床。

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引用次数: 0

Pipeline: Therapeutics – Two views of off-label use 管道：治疗学-超说明书使用的两种观点

IF 5.9 1区医学 Q1 OPHTHALMOLOGY

Ocular Surface

Pub Date : 2025-04-10 DOI: 10.1016/j.jtos.2025.04.005

Gary D. Novack

引用次数: 0

Acanthamoeba keratitis treatment outcomes compared for drug delivery by protocol versus physician's individualised treatment 棘阿米巴角膜炎的治疗结果比较方案给药与医生个体化治疗。

IF 5.9 1区医学 Q1 OPHTHALMOLOGY

Ocular Surface

Pub Date : 2025-04-07 DOI: 10.1016/j.jtos.2025.03.008

John K.G. Dart , Vincenzo Papa , Paolo Rama , Karl Anders Knutsson , Saj Ahmad , Scott Hau , Sara Sanchez , Antonella Franch , Federica Birattari , Pia Leon , Adriano Fasolo , Ewa Mrukwa-Kominek , Katarzyna Jadczyk-Sorek , Fiona Carley , Hossain Parwez , Darwin C. Minassian

Purpose

To compare Acanthamoeba keratitis (AK) outcomes for treatment delivered using a detailed protocol versus physician's individualised treatment.

Methods

This double cohort study compared the outcomes of these different delivery methods for PHMB 0.02 % and diamidine 0.1 % dual therapy. The primary outcome was the medical cure rate without surgery within 12 months (MCR_12) and the secondary was visual acuity. Any change of treatment, any surgery, or treatment for >12 months was a failure. Outcomes were both unadjusted and adjusted, using multivariable analysis, for baseline differences affecting outcomes. Patients were from two centres in Milan and London treated at different times; the individualised cohort (1991–2012) and per-protocol cohort (2017–2021).

Results

The individualised cohort included 96 and the per-protocol 47 patients. Both unadjusted and adjusted results were similar. The unadjusted outcomes for both centres combined showed significantly improved outcomes for per-protocol treatment with a 1.59-fold improvement in MCR_12 (95 % CI 1.40–1.80, p < 0.001) and a 2.1-fold increase in visual acuity ≥20/25 (95 % CI 1.34–3.29, p < 0.001). Amongst potential confounding factors examined, neither baseline AK disease stage, treatment centre nor the type of diamidine significantly influenced outcomes.

Conclusions

This study shows significant advantages for the use of protocol delivered versus individualised treatment for AK. The use of evidence-based treatment delivery protocols, like the one used here for AK, might improve outcomes for all causes of microbial keratitis and could offer practitioners and patients the benefit of having an easy-to-follow drug delivery protocol, with known outcomes.

目的：比较棘阿米巴角膜炎（AK）的治疗结果提供了一个详细的方案和医生的个体化治疗。方法：本双队列研究比较了0.02% PHMB和0.1%二胺双重治疗的不同给药方式的结果。主要观察指标为12个月内不手术治愈率（MCR_12），次要观察指标为视力。任何治疗方法的改变，任何手术，或长达12个月的治疗都是失败的。采用多变量分析，对影响结果的基线差异进行了未调整和调整。来自米兰和伦敦两个中心的患者在不同时间接受治疗；个体化队列（1991-2012）和按方案队列（2017-2021）。结果：个体化队列96例，按方案47例。未调整和调整后的结果相似。两个中心未经调整的合并结果显示，按方案治疗的结果显著改善，MCR_12改善1.59倍（95% CI 1.40 - 1.80, p < 0.001），视力≥20/25增加2.1倍（95% CI 1.34 - 3.29, p < 0.001）。在检查的潜在混杂因素中，基线AK疾病分期、治疗中心和二胺类型均未显著影响结果。结论：这项研究显示了使用方案传递与个性化治疗AK的显著优势。使用循证治疗方案，如这里使用的AK，可能会改善所有原因的微生物角膜炎的结果，并可以为医生和患者提供一个易于遵循的药物给药方案，已知的结果。

{"title":"Acanthamoeba keratitis treatment outcomes compared for drug delivery by protocol versus physician's individualised treatment","authors":"John K.G. Dart , Vincenzo Papa , Paolo Rama , Karl Anders Knutsson , Saj Ahmad , Scott Hau , Sara Sanchez , Antonella Franch , Federica Birattari , Pia Leon , Adriano Fasolo , Ewa Mrukwa-Kominek , Katarzyna Jadczyk-Sorek , Fiona Carley , Hossain Parwez , Darwin C. Minassian","doi":"10.1016/j.jtos.2025.03.008","DOIUrl":"10.1016/j.jtos.2025.03.008","url":null,"abstract":"<div><h3>Purpose</h3><div>To compare Acanthamoeba keratitis (AK) outcomes for treatment delivered using a detailed protocol versus physician's individualised treatment.</div></div><div><h3>Methods</h3><div>This double cohort study compared the outcomes of these different delivery methods for PHMB 0.02 % and diamidine 0.1 % dual therapy. The primary outcome was the medical cure rate without surgery within 12 months (MCR_12) and the secondary was visual acuity. Any change of treatment, any surgery, or treatment for >12 months was a failure. Outcomes were both unadjusted and adjusted, using multivariable analysis, for baseline differences affecting outcomes. Patients were from two centres in Milan and London treated at different times; the individualised cohort (1991–2012) and per-protocol cohort (2017–2021).</div></div><div><h3>Results</h3><div>The individualised cohort included 96 and the per-protocol 47 patients. Both unadjusted and adjusted results were similar. The unadjusted outcomes for both centres combined showed significantly improved outcomes for per-protocol treatment with a 1.59-fold improvement in MCR_12 (95 % CI 1.40–1.80, p < 0.001) and a 2.1-fold increase in visual acuity ≥20/25 (95 % CI 1.34–3.29, p < 0.001). Amongst potential confounding factors examined, neither baseline AK disease stage, treatment centre nor the type of diamidine significantly influenced outcomes.</div></div><div><h3>Conclusions</h3><div>This study shows significant advantages for the use of protocol delivered versus individualised treatment for AK. The use of evidence-based treatment delivery protocols, like the one used here for AK, might improve outcomes for all causes of microbial keratitis and could offer practitioners and patients the benefit of having an easy-to-follow drug delivery protocol, with known outcomes.</div></div>","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":"38 ","pages":"Pages 132-141"},"PeriodicalIF":5.9,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144002474","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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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