Ocular Surface最新文献_第4页

Clinical and genetic profiling of fibromyalgia-associated dry eye: A multifactorial approach 纤维肌痛相关干眼的临床和基因分析：一种多因素方法

IF 5.6 1区医学 Q1 OPHTHALMOLOGY

Ocular Surface

Pub Date : 2025-10-01 DOI: 10.1016/j.jtos.2025.10.012

Carlos Vergés , Ana Giménez-Capitán , Verónica Ribas , Elizabeth Martínez-Pérez , María José González , Francesc March de Ribot , Noelia Armiger-Borras , Andrea Caycedo , Cristina Rodríguez-Muñoz , Cayetano Alegre , Susana Muñoz , José Salgado-Borges , Clara Mayo-de-las-Casas

Background

Fibromyalgia syndrome (FM) is a chronic pain disorder affecting 3–6 % of the global population, often underdiagnosed and lacking specific diagnostic tests. Many patients also present with dry eye disease (DED), suggesting a possible link. This study explores the relationship between DED and FM-associated DED (FM-DED) by evaluating corneal nerve abnormalities using in vivo corneal confocal microscopy (IVCM), alongside gene expression and polymorphisms (COMT, MTHFR) related to inflammation.

Methods

The study included 113 participants: 81 patients (44 with DED, 37 with FM-DED) and 32 healthy controls (HC). Cell lines SK-OV-3, NCI-H1781, and NCI-H460 were included as controls. Clinical evaluations, IVCM, and genotyping of COMT Val158Met and MTHFR C677T from blood samples were conducted. Conjunctival gene expression was analyzed using an nCounter custom panel of 77 genes. Protein–Protein Interaction (PPI) network analysis identified key biological processes.

Results

FM-DED patients showed significantly reduced corneal nerve density and increased Langerhans cells and microneuromas, with strong correlation with pain ((|ρ| > 0.7). Significant differences were observed in OSDI, NITBUT, TMH, and meibomian gland atrophy, but not in osmolarity or Schirmer I test. The GA genotype of COMT Val158Met was more frequent in FM-DED (60 %) and associated with severe cases. The CT genotype of MTHFR C677T was linked to increased corneal damage. Gene expression analysis showed immune-related gene overexpression (MUC1, IFITM1, PSMB8), with FM-DED-specific upregulation of PIGR and CEACAM6. PPI analysis highlighted lipopolysaccharide-mediated signaling.

Conclusions

Genetic polymorphisms and immune dysregulation contribute to FM-DED pathophysiology, supporting the need for differentiated diagnosis and targeted therapies.

纤维肌痛综合征（FM）是一种慢性疼痛疾病，影响全球3 - 6%的人口，通常诊断不足，缺乏特定的诊断测试。许多患者还出现干眼症（DED），提示两者之间可能存在联系。本研究通过使用体内角膜共聚焦显微镜（IVCM）评估角膜神经异常，以及与炎症相关的基因表达和多态性（COMT， MTHFR），探讨了DED和fm相关性DED （FM-DED）之间的关系。方法纳入113例患者：81例（DED 44例，FM-DED 37例），32例健康对照（HC）。将SK-OV-3、NCI-H1781和NCI-H460细胞系作为对照。临床评估、IVCM和血液样本COMT Val158Met和MTHFR C677T基因分型。使用nCounter定制的77个基因面板分析结膜基因表达。蛋白质-蛋白质相互作用（PPI）网络分析确定了关键的生物过程。结果fm - ded患者角膜神经密度明显降低，朗格汉斯细胞和微神经瘤增加，与疼痛有很强的相关性(（|ρ| > 0.7）。在OSDI、NITBUT、TMH和睑板腺萎缩中观察到显著差异，但在渗透压和Schirmer I试验中没有观察到显著差异。COMT Val158Met的GA基因型在FM-DED中更为常见（60%），并与重症病例相关。MTHFR C677T的CT基因型与角膜损伤增加有关。基因表达分析显示免疫相关基因MUC1、IFITM1、PSMB8过表达，并伴有fm - ed特异性的PIGR和CEACAM6上调。PPI分析强调脂多糖介导的信号传导。结论遗传多态性和免疫失调参与了FM-DED的病理生理，支持了鉴别诊断和靶向治疗的必要性。

{"title":"Clinical and genetic profiling of fibromyalgia-associated dry eye: A multifactorial approach","authors":"Carlos Vergés , Ana Giménez-Capitán , Verónica Ribas , Elizabeth Martínez-Pérez , María José González , Francesc March de Ribot , Noelia Armiger-Borras , Andrea Caycedo , Cristina Rodríguez-Muñoz , Cayetano Alegre , Susana Muñoz , José Salgado-Borges , Clara Mayo-de-las-Casas","doi":"10.1016/j.jtos.2025.10.012","DOIUrl":"10.1016/j.jtos.2025.10.012","url":null,"abstract":"<div><h3>Background</h3><div>Fibromyalgia syndrome (FM) is a chronic pain disorder affecting 3–6 % of the global population, often underdiagnosed and lacking specific diagnostic tests. Many patients also present with dry eye disease (DED), suggesting a possible link. This study explores the relationship between DED and FM-associated DED (FM-DED) by evaluating corneal nerve abnormalities using in vivo corneal confocal microscopy (IVCM), alongside gene expression and polymorphisms (<em>COMT</em>, <em>MTHFR</em>) related to inflammation.</div></div><div><h3>Methods</h3><div>The study included 113 participants: 81 patients (44 with DED, 37 with FM-DED) and 32 healthy controls (HC). Cell lines SK-OV-3, NCI-H1781, and NCI-H460 were included as controls. Clinical evaluations, IVCM, and genotyping of <em>COMT</em> Val158Met and <em>MTHFR</em> C677T from blood samples were conducted. Conjunctival gene expression was analyzed using an nCounter custom panel of 77 genes. Protein–Protein Interaction (PPI) network analysis identified key biological processes.</div></div><div><h3>Results</h3><div>FM-DED patients showed significantly reduced corneal nerve density and increased Langerhans cells and microneuromas, with strong correlation with pain ((|ρ| > 0.7). Significant differences were observed in OSDI, NITBUT, TMH, and meibomian gland atrophy, but not in osmolarity or Schirmer I test. The GA genotype of <em>COMT</em> Val158Met was more frequent in FM-DED (60 %) and associated with severe cases. The CT genotype of MTHFR C677T was linked to increased corneal damage. Gene expression analysis showed immune-related gene overexpression (<em>MUC1, IFITM1, PSMB8</em>), with FM-DED-specific upregulation of <em>PIGR</em> and <em>CEACAM6</em>. PPI analysis highlighted lipopolysaccharide-mediated signaling.</div></div><div><h3>Conclusions</h3><div>Genetic polymorphisms and immune dysregulation contribute to FM-DED pathophysiology, supporting the need for differentiated diagnosis and targeted therapies.</div></div>","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":"38 ","pages":"Pages 377-387"},"PeriodicalIF":5.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145412014","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

Letter to the editor regarding “Simple limbal epithelial transplantation versus cultivated limbal epithelial transplantation in ocular burns" 致编辑关于“单纯角膜缘上皮移植与培养角膜缘上皮移植治疗眼部烧伤”的信。

IF 5.6 1区医学 Q1 OPHTHALMOLOGY

Ocular Surface

Pub Date : 2025-10-01 DOI: 10.1016/j.jtos.2025.07.006

Mehmet Gurdal , Ozlem Barut Selver

引用次数: 0

Eye pain and ocular surface characteristics in Postural Orthostatic Tachycardia Syndrome (POTS): The role of autonomic dysfunction 体位性心动过速综合征（POTS）的眼痛和眼表特征：自主神经功能障碍的作用

IF 5.6 1区医学 Q1 OPHTHALMOLOGY

Ocular Surface

Pub Date : 2025-10-01 DOI: 10.1016/j.jtos.2025.10.009

Sezen Karakus , Jane Jin Huang , Meltem Yashar , Meron Haile , Ugur Tunc , Claudia Viton , Stefan Cehan , Pranav Kotamraju , Cynthia Wang , Brittany L. Adler , Tae H. Chung

Purpose

Postural Orthostatic Tachycardia Syndrome (POTS), an autonomic nervous system dysfunction, is frequently associated with ocular symptoms including pain and dryness. This study aimed to characterize ocular surface findings in POTS patients to clarify whether these symptoms reflect classic dry eye disease or altered sensory processing related to autonomic dysfunction.

Methods

A retrospective observational study was conducted on patients with confirmed POTS who underwent standardized ocular surface evaluations at a tertiary academic center between 2019 and 2024. Demographics and medical history were extracted from records. Assessments included pain ratings (0–10 Likert scale), proparacaine response, Schirmer testing, ocular staining score (OSS), and in vivo confocal microscopy (IVCM) when available.

Results

Forty-three patients (39 females; mean age 45.1 ± 14.0 years) were included. Thirty-eight reported ocular pain and dryness. Among 21 patients with recorded pain scores, the median (IQR) was 5 (4), reduced to 4 (4.5) after proparacaine. Median Schirmer score was 5 mm (IQR 27), with 13 patients ≤5 mm. Median OSS was 0 (IQR 2), with only 4 patients showing OSS>1 with improved symptoms after proparacaine, suggesting neuropathic etiology in 34 patients. IVCM, available in six cases, revealed reduced nerve density and microneuromas. Migraine was the most common comorbidity (76.7 %) and was strongly associated with pain without staining (OR = 15.0; 95 % CI 2.65–85.0; p = 0.002).

Conclusions

POTS patients frequently report ocular pain and dryness, yet objective signs of dry eye are uncommon. These findings underscore the need for ocular surface staining to distinguish dry eye disease from neuropathic ocular pain, suggesting that altered corneal nerve function in autonomic dysfunction may drive symptoms.

目的体位性站立性心动过速综合征（POTS）是一种自主神经系统功能障碍，常伴有眼部症状，包括疼痛和干燥。本研究旨在描述POTS患者的眼表表现，以阐明这些症状是否反映了典型的干眼病或与自主神经功能障碍相关的感觉处理改变。方法对2019 - 2024年在某三级学术中心进行标准化眼表评估的确诊POTS患者进行回顾性观察研究。从记录中提取人口统计和病史。评估包括疼痛评分（0-10李克特量表）、丙帕卡因反应、Schirmer试验、眼染色评分（OSS）和体内共聚焦显微镜（IVCM）（如果有的话）。结果纳入43例患者，其中女性39例，平均年龄45.1±14.0岁。38人报告眼部疼痛和干涩。在21例有疼痛评分记录的患者中，中位数（IQR）为5(4)，经丙帕卡因后降至4（4.5）。中位Schirmer评分为5 mm (IQR 27)， 13例患者≤5 mm。中位OSS为0 (IQR 2)，只有4例患者出现OSS>；1例患者经丙帕卡因后症状改善，提示34例患者的病因为神经性病变。6例IVCM显示神经密度降低和微神经瘤。偏头痛是最常见的合并症（76.7%），与无染色疼痛密切相关（OR = 15.0; 95% CI 2.65-85.0; p = 0.002）。结论斑点患者常报告眼部疼痛和干涩，但干眼的客观体征并不常见。这些发现强调了通过眼表染色来区分干眼病和神经性眼痛的必要性，表明自主神经功能障碍导致的角膜神经功能改变可能驱动症状。

{"title":"Eye pain and ocular surface characteristics in Postural Orthostatic Tachycardia Syndrome (POTS): The role of autonomic dysfunction","authors":"Sezen Karakus , Jane Jin Huang , Meltem Yashar , Meron Haile , Ugur Tunc , Claudia Viton , Stefan Cehan , Pranav Kotamraju , Cynthia Wang , Brittany L. Adler , Tae H. Chung","doi":"10.1016/j.jtos.2025.10.009","DOIUrl":"10.1016/j.jtos.2025.10.009","url":null,"abstract":"<div><h3>Purpose</h3><div>Postural Orthostatic Tachycardia Syndrome (POTS), an autonomic nervous system dysfunction, is frequently associated with ocular symptoms including pain and dryness. This study aimed to characterize ocular surface findings in POTS patients to clarify whether these symptoms reflect classic dry eye disease or altered sensory processing related to autonomic dysfunction.</div></div><div><h3>Methods</h3><div>A retrospective observational study was conducted on patients with confirmed POTS who underwent standardized ocular surface evaluations at a tertiary academic center between 2019 and 2024. Demographics and medical history were extracted from records. Assessments included pain ratings (0–10 Likert scale), proparacaine response, Schirmer testing, ocular staining score (OSS), and in vivo confocal microscopy (IVCM) when available.</div></div><div><h3>Results</h3><div>Forty-three patients (39 females; mean age 45.1 ± 14.0 years) were included. Thirty-eight reported ocular pain and dryness. Among 21 patients with recorded pain scores, the median (IQR) was 5 (4), reduced to 4 (4.5) after proparacaine. Median Schirmer score was 5 mm (IQR 27), with 13 patients ≤5 mm. Median OSS was 0 (IQR 2), with only 4 patients showing OSS>1 with improved symptoms after proparacaine, suggesting neuropathic etiology in 34 patients. IVCM, available in six cases, revealed reduced nerve density and microneuromas. Migraine was the most common comorbidity (76.7 %) and was strongly associated with pain without staining (OR = 15.0; 95 % CI 2.65–85.0; p = 0.002).</div></div><div><h3>Conclusions</h3><div>POTS patients frequently report ocular pain and dryness, yet objective signs of dry eye are uncommon. These findings underscore the need for ocular surface staining to distinguish dry eye disease from neuropathic ocular pain, suggesting that altered corneal nerve function in autonomic dysfunction may drive symptoms.</div></div>","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":"38 ","pages":"Pages 359-364"},"PeriodicalIF":5.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145382684","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

Predictors of vision-related quality of life in patients treated for filamentous fungal keratitis 丝状真菌性角膜炎患者视力相关生活质量的预测因素。

IF 5.6 1区医学 Q1 OPHTHALMOLOGY

Ocular Surface

Pub Date : 2025-10-01 DOI: 10.1016/j.jtos.2025.09.001

N.V. Prajna , N. Radhakrishnan , Prajna Lalitha , Revathi Rajaraman , Sarah Abdelrahman , Benjamin F. Arnold , Thomas M. Lietman , Jennifer Rose-Nussbaumer , Alejandro Arboleda

Purpose

To identify clinical characteristics that predict vision-related quality of life (QoL) in patients with fungal keratitis three months after treatment.

Methods

Patients with fungal keratitis enrolled in the Cross-Linking Assisted Infection Reduction trial were treated with topical natamycin 5 % or amphotericin 0.15 %, with or without adjuvant corneal cross-linking (CXL). Demographic data, ulcer characteristics, clinical course, and responses to the Indian Visual Function Questionnaire (IND-VFQ) were collected at baseline and follow-up. Logistic regression models were used to assess factors associated with patient-reported vision-related QoL at three months. Analyses included the average IND-VFQ score as well as Rasch-derived subscale scores for vision-specific mobility, activity limitation, psychosocial impact, and visual symptoms.

Results

Of 111 participants enrolled, 86 had complete data at both timepoints. Multivariable models identified baseline IND-VFQ score, scar size, and presence of hypopyon as significant predictors of 3-month IND-VFQ scores. A 1-point change in best spectacle corrected visual acuity is correlated with a 13.4-point change in the opposite direction in average IND-VFQ (P=0.001). Patients with adverse events requiring surgery had lower 3-month IND-VFQ scores than those managed medically (P=0.001). Ulcer characteristics including location, depth, symptom duration, repeat culture positivity, organism type, and fungal genus were not associated with final IND-VFQ scores.

Conclusions

Vision-related QoL after fungal keratitis is significantly influenced by change in visual acuity, need for surgical intervention, and select baseline factors including scar size, initial IND-VFQ score, and presence of hypopyon. Vision-related QoL did not differ by antifungal treatment or adjuvant CXL use.

目的：确定预测真菌性角膜炎患者治疗后3个月视力相关生活质量（QoL）的临床特征。方法：参加交联辅助减少感染试验的真菌性角膜炎患者接受5%纳他霉素或0.15%两性霉素外用治疗，伴或不伴角膜交联（CXL）。在基线和随访时收集人口统计数据、溃疡特征、临床病程和对印度视觉功能问卷（IND-VFQ）的反应。使用逻辑回归模型评估与患者报告的三个月视力相关生活质量相关的因素。分析包括IND-VFQ的平均得分以及rasch衍生的视觉特异性活动能力、活动限制、社会心理影响和视觉症状的亚量表得分。结果：在111名参与者中，86名在两个时间点都有完整的数据。多变量模型确定基线IND-VFQ评分、疤痕大小和假说的存在是3个月IND-VFQ评分的重要预测因素。最佳眼镜矫正视力变化1点与平均IND-VFQ相反方向变化13.4点相关（P=0.001）。需要手术的不良事件患者的3个月IND-VFQ评分低于药物治疗的患者（P=0.001）。溃疡特征包括位置、深度、症状持续时间、重复培养阳性、生物体类型和真菌属与最终IND-VFQ评分无关。结论：真菌性角膜炎术后的视力相关生活质量受视力变化、手术干预需要、疤痕大小、初始IND-VFQ评分、是否存在垂体后叶等基线因素的影响。抗真菌治疗或辅助使用CXL对视力相关的生活质量没有影响。

{"title":"Predictors of vision-related quality of life in patients treated for filamentous fungal keratitis","authors":"N.V. Prajna , N. Radhakrishnan , Prajna Lalitha , Revathi Rajaraman , Sarah Abdelrahman , Benjamin F. Arnold , Thomas M. Lietman , Jennifer Rose-Nussbaumer , Alejandro Arboleda","doi":"10.1016/j.jtos.2025.09.001","DOIUrl":"10.1016/j.jtos.2025.09.001","url":null,"abstract":"<div><h3>Purpose</h3><div>To identify clinical characteristics that predict vision-related quality of life (QoL) in patients with fungal keratitis three months after treatment.</div></div><div><h3>Methods</h3><div>Patients with fungal keratitis enrolled in the Cross-Linking Assisted Infection Reduction trial were treated with topical natamycin 5 % or amphotericin 0.15 %, with or without adjuvant corneal cross-linking (CXL). Demographic data, ulcer characteristics, clinical course, and responses to the Indian Visual Function Questionnaire (IND-VFQ) were collected at baseline and follow-up. Logistic regression models were used to assess factors associated with patient-reported vision-related QoL at three months. Analyses included the average IND-VFQ score as well as Rasch-derived subscale scores for vision-specific mobility, activity limitation, psychosocial impact, and visual symptoms.</div></div><div><h3>Results</h3><div>Of 111 participants enrolled, 86 had complete data at both timepoints. Multivariable models identified baseline IND-VFQ score, scar size, and presence of hypopyon as significant predictors of 3-month IND-VFQ scores. A 1-point change in best spectacle corrected visual acuity is correlated with a 13.4-point change in the opposite direction in average IND-VFQ (P=0.001). Patients with adverse events requiring surgery had lower 3-month IND-VFQ scores than those managed medically (P=0.001). Ulcer characteristics including location, depth, symptom duration, repeat culture positivity, organism type, and fungal genus were not associated with final IND-VFQ scores.</div></div><div><h3>Conclusions</h3><div>Vision-related QoL after fungal keratitis is significantly influenced by change in visual acuity, need for surgical intervention, and select baseline factors including scar size, initial IND-VFQ score, and presence of hypopyon. Vision-related QoL did not differ by antifungal treatment or adjuvant CXL use.</div></div>","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":"38 ","pages":"Pages 319-323"},"PeriodicalIF":5.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145180773","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

Amniotic membrane transplantation techniques in acute ocular Stevens-Johnson syndrome and toxic epidermal necrolysis: A systematic review 羊膜移植技术治疗急性史蒂文斯-约翰逊综合征和中毒性表皮坏死松解：系统综述。

IF 5.6 1区医学 Q1 OPHTHALMOLOGY

Ocular Surface

Pub Date : 2025-10-01 DOI: 10.1016/j.jtos.2025.10.002

Jai Paris , Carmelo Macri , Abdullah I. Almater , James Slattery , Dinesh Selva

Ocular involvement in Stevens-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TENS) is common and can result in severe acute inflammation and long-term complications. Early intervention with amniotic membrane transplantation (AMT) is essential to preserve long term ocular surface integrity and function. This review aimed to evaluate and compare the different surgical techniques to AMT in the acute phase of SJS/TENS, covering sutured, glued, and sutureless/glueless approaches. A systematic search of PubMed, MEDLINE, Embase, Scopus, Cochrane, Google Scholar, and reference lists identified 630 articles, with 27 studies meeting inclusion criteria. Sutured AMT remains the most commonly used method due to its ability to provide comprehensive ocular surface coverage, however is time-consuming and often requires general anaesthesia. Glued AMT, using fibrin or cyanoacrylate adhesive, offers a faster, less invasive alternative suitable for bedside application, though evidence in SJS/TENS is limited. Sutureless/glueless options such as the Prokera® enable rapid deployment and patient comfort but do not provide full ocular surface protection and should only be usedas adjuncts. Hybrid glued approaches with limited suturing may be appropriate for extensive coverage with bedside application. Overall, the choice of technique depends on the extent of ocular involvement, patient stability, and available resources. Further studies are needed to directly compare outcomes across different AMT approaches in acute ocular SJS/TENS.

史蒂文斯-约翰逊综合征（SJS）和中毒性表皮坏死松解（TENS）的眼部受累是常见的，可导致严重的急性炎症和长期并发症。早期干预羊膜移植（AMT）是必要的，以保持长期的眼表完整性和功能。本综述旨在评估和比较SJS/TENS急性期AMT的不同手术技术，包括缝合、胶合和无缝合/无胶合入路。对PubMed， MEDLINE, Embase, Scopus, Cochrane，谷歌Scholar和参考文献列表进行系统搜索，确定了630篇文章，其中27篇研究符合纳入标准。缝合AMT仍然是最常用的方法，因为它能够提供全面的眼表覆盖，但是耗时且通常需要全身麻醉。使用纤维蛋白或氰基丙烯酸酯胶粘剂的胶合AMT提供了一种更快速、侵入性更小的替代方案，适用于床边应用，尽管在SJS/TENS中的证据有限。无缝合线/无胶水的选择，如Prokera®，可以快速部署和患者舒适，但不能提供完整的眼表保护，只能作为辅助工具使用。混合胶合方法与有限的缝合可能适用于广泛覆盖的床边应用。总的来说，技术的选择取决于眼部受累程度、患者的稳定性和可用的资源。需要进一步的研究来直接比较不同AMT入路治疗急性眼部SJS/TENS的结果。

{"title":"Amniotic membrane transplantation techniques in acute ocular Stevens-Johnson syndrome and toxic epidermal necrolysis: A systematic review","authors":"Jai Paris , Carmelo Macri , Abdullah I. Almater , James Slattery , Dinesh Selva","doi":"10.1016/j.jtos.2025.10.002","DOIUrl":"10.1016/j.jtos.2025.10.002","url":null,"abstract":"<div><div>Ocular involvement in Stevens-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TENS) is common and can result in severe acute inflammation and long-term complications. Early intervention with amniotic membrane transplantation (AMT) is essential to preserve long term ocular surface integrity and function. This review aimed to evaluate and compare the different surgical techniques to AMT in the acute phase of SJS/TENS, covering sutured, glued, and sutureless/glueless approaches. A systematic search of PubMed, MEDLINE, Embase, Scopus, Cochrane, Google Scholar, and reference lists identified 630 articles, with 27 studies meeting inclusion criteria. Sutured AMT remains the most commonly used method due to its ability to provide comprehensive ocular surface coverage, however is time-consuming and often requires general anaesthesia. Glued AMT, using fibrin or cyanoacrylate adhesive, offers a faster, less invasive alternative suitable for bedside application, though evidence in SJS/TENS is limited. Sutureless/glueless options such as the Prokera® enable rapid deployment and patient comfort but do not provide full ocular surface protection and should only be usedas adjuncts. Hybrid glued approaches with limited suturing may be appropriate for extensive coverage with bedside application. Overall, the choice of technique depends on the extent of ocular involvement, patient stability, and available resources. Further studies are needed to directly compare outcomes across different AMT approaches in acute ocular SJS/TENS.</div></div>","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":"38 ","pages":"Pages 337-358"},"PeriodicalIF":5.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145305134","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

Letter to the Editor regarding “Corneal sensory nerve regulation of tear production through stimulation of transient receptor potential melastatin 8 (TRPM8) channel: A potential new approach for treating dry eye disease” 致编辑关于“角膜感觉神经通过刺激瞬时受体电位美拉他汀8 （TRPM8）通道调节泪液产生：一种治疗干眼病的潜在新方法”的信

IF 5.6 1区医学 Q1 OPHTHALMOLOGY

Ocular Surface

Pub Date : 2025-09-20 DOI: 10.1016/j.jtos.2025.09.002

Parth Aphale, Shashank Dokania, Himanshu Shekhar

引用次数: 0

Downregulation of the core circadian gene Nr1d2 in the lacrimal gland contributes to postoperative dry eye disease by impairing lipid metabolism 泪腺核心昼夜节律基因Nr1d2的下调通过损害脂质代谢参与术后干眼病

IF 5.6 1区医学 Q1 OPHTHALMOLOGY

Ocular Surface

Pub Date : 2025-08-28 DOI: 10.1016/j.jtos.2025.08.009

Shiji Liu , Yuke Huang , Xi Chen , Huanhuan Ren, Jiaxin Chen, Qingqing Mu, Jiejie Zhuang, Yan Li, Jin Qiu, Keming Yu, Jing Zhuang

Purpose

Dry eye disease (DED) is a prevalent complication after refractive surgery, and its underlying mechanisms are not fully understood. Given that circadian rhythm tightly regulates tear secretion, this study aims to investigate the circadian changes in the lacrimal gland after corneal refractive surgery and the associated mechanisms.

Methods

C57/BL6 mice underwent corneal epithelial abrasion and stromal severing. DED was assessed using phenol red thread and fluorescein staining. RNA sequencing identified differentially expressed genes (DEGs) related to circadian rhythm, validated by RT-qPCR and Western blotting. Immunofluorescence, TUNEL staining, untargeted metabolomics, Oil-Red-O staining, and TEM were performed to analyze the lacrimal gland changes. Clinically, DED symptoms were evaluated using the OSDI questionnaire in 867 post-surgical patients and 705 controls.

Results

Corneal epithelial abrasion and stromal severing induced DED symptoms and lacrimal dysfunction, including reduced tear volume, ocular surface inflammation, and lacrimal pathophysiological changes. Nr1d2, the key circadian rhythm gene, was significantly down-regulated in the lacrimal gland compared to the control. Activation of Nr1d2 with SR9011 restored the lacrimal gland function and alleviated DED symptoms. Furthermore, the down-regulation of Nr1d2 significantly impaired lipid metabolism and mitochondrial function in the lacrimal gland, which SR9011 reversed. Clinically, the incidence of DED was markedly higher in the surgical cohort, with symptom occurrence exhibiting diurnal variation and peaking in the early morning and late evening.

Conclusions

Disruption of circadian rhythms, specifically Nr1d2 downregulation, contributes to post-surgical DED. Targeting Nr1d2 may offer a novel therapeutic approach to restore lacrimal gland function and alleviate DED.

目的：干眼病是屈光手术后常见的并发症，其发病机制尚不完全清楚。鉴于昼夜节律紧密调控泪液分泌，本研究旨在探讨角膜屈光手术后泪腺的昼夜节律变化及其机制。方法：对C57/BL6小鼠进行角膜上皮磨损和间质切断。采用酚红线和荧光素染色评价DED。RNA测序鉴定出与昼夜节律相关的差异表达基因（DEGs），并通过RT-qPCR和Western blotting验证。采用免疫荧光、TUNEL染色、非靶向代谢组学、Oil-Red-O染色和透射电镜分析泪腺的变化。临床应用OSDI问卷对867例术后患者和705例对照患者进行DED症状评估。结果：角膜上皮磨损和间质损伤引起DED症状和泪液功能障碍，包括泪液量减少、眼表炎症和泪液病理生理改变。与对照组相比，关键的昼夜节律基因Nr1d2在泪腺中显著下调。SR9011激活Nr1d2恢复泪腺功能，缓解DED症状。此外，Nr1d2的下调显著损害了泪腺的脂质代谢和线粒体功能，SR9011逆转了这一变化。临床上，手术组DED的发生率明显较高，且症状呈现昼夜变化，在清晨和傍晚达到高峰。结论：昼夜节律的破坏，特别是Nr1d2的下调，有助于术后DED。靶向Nr1d2可能为恢复泪腺功能和缓解DED提供新的治疗途径。

{"title":"Downregulation of the core circadian gene Nr1d2 in the lacrimal gland contributes to postoperative dry eye disease by impairing lipid metabolism","authors":"Shiji Liu , Yuke Huang , Xi Chen , Huanhuan Ren, Jiaxin Chen, Qingqing Mu, Jiejie Zhuang, Yan Li, Jin Qiu, Keming Yu, Jing Zhuang","doi":"10.1016/j.jtos.2025.08.009","DOIUrl":"10.1016/j.jtos.2025.08.009","url":null,"abstract":"<div><h3>Purpose</h3><div>Dry eye disease (DED) is a prevalent complication after refractive surgery, and its underlying mechanisms are not fully understood. Given that circadian rhythm tightly regulates tear secretion, this study aims to investigate the circadian changes in the lacrimal gland after corneal refractive surgery and the associated mechanisms.</div></div><div><h3>Methods</h3><div>C57/BL6 mice underwent corneal epithelial abrasion and stromal severing. DED was assessed using phenol red thread and fluorescein staining. RNA sequencing identified differentially expressed genes (DEGs) related to circadian rhythm, validated by RT-qPCR and Western blotting. Immunofluorescence, TUNEL staining, untargeted metabolomics, Oil-Red-O staining, and TEM were performed to analyze the lacrimal gland changes. Clinically, DED symptoms were evaluated using the OSDI questionnaire in 867 post-surgical patients and 705 controls.</div></div><div><h3>Results</h3><div>Corneal epithelial abrasion and stromal severing induced DED symptoms and lacrimal dysfunction, including reduced tear volume, ocular surface inflammation, and lacrimal pathophysiological changes. Nr1d2, the key circadian rhythm gene, was significantly down-regulated in the lacrimal gland compared to the control. Activation of Nr1d2 with SR9011 restored the lacrimal gland function and alleviated DED symptoms. Furthermore, the down-regulation of Nr1d2 significantly impaired lipid metabolism and mitochondrial function in the lacrimal gland, which SR9011 reversed. Clinically, the incidence of DED was markedly higher in the surgical cohort, with symptom occurrence exhibiting diurnal variation and peaking in the early morning and late evening.</div></div><div><h3>Conclusions</h3><div>Disruption of circadian rhythms, specifically Nr1d2 downregulation, contributes to post-surgical DED. Targeting Nr1d2 may offer a novel therapeutic approach to restore lacrimal gland function and alleviate DED.</div></div>","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":"38 ","pages":"Pages 290-301"},"PeriodicalIF":5.6,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144984708","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

L009 peptide as a novel antiangiogenic agent for corneal neovascularization via regulation of the TNFSF15-VEGF axis L009肽通过调节TNFSF15-VEGF轴作为角膜新生血管的新型抗血管生成剂

IF 5.6 1区医学 Q1 OPHTHALMOLOGY

Ocular Surface

Pub Date : 2025-08-27 DOI: 10.1016/j.jtos.2025.08.008

Ke Yan , Yiran Yang , Yi Han , Yuhan Zhang , Tong Zhou , Wenxin Sun , Ruochen Wang , Zhaolin Liu , Qinghe Zhang , Linfangzi Zhu , Meidi Tan , Caihong Huang , Jiaoyue Hu , Qiuping Liu , Zhaoqiang Zhang , Zuguo Liu

Corneal neovascularization (CNV) is a leading cause of vision impairment, with existing therapeutic options offering limited efficacy. This study presents L009, a novel antiangiogenic agent derived from the Kringle 5 domain of human plasminogen, specifically a heptapeptide, designed to treat CNV. In preclinical models, L009 demonstrated substantial efficacy by markedly inhibiting endothelial cell proliferation and migration, reducing vascular permeability, and maintaining ocular safety. Mechanistically, L009 exerts its effects by upregulating tumor necrosis factor superfamily member 15 (TNFSF15), downregulating vascular endothelial growth factor receptor 2 (VEGFR2), and increasing the expression of soluble VEGFR1. These actions restore vascular homeostasis and enhance vascular stability through the upregulation of the tight junction protein VE-cadherin. By specifically targeting the TNFSF15-VEGF axis, L009 offers a distinctive therapeutic approach, differentiating it from conventional anti-VEGF therapies. Its dual action of anti-angiogenesis and promotion of vascular stability highlights its potential as a next-generation treatment for CNV. Further investigation into its long-term efficacy and potential for synergy with existing therapies is warranted.

角膜新生血管（CNV）是视力损害的主要原因，现有的治疗方案提供有限的疗效。本研究提出了一种新型抗血管生成药物L009，该药物来源于人纤溶酶原的Kringle 5结构域，特别是一种七肽，旨在治疗CNV。在临床前模型中，L009通过显著抑制内皮细胞增殖和迁移，降低血管通透性，维持眼部安全，显示出实质性的疗效。在机制上，L009通过上调肿瘤坏死因子超家族成员15 (TNFSF15)，下调血管内皮生长因子受体2 (VEGFR2)，增加可溶性VEGFR1的表达来发挥作用。这些作用通过上调紧密连接蛋白ve -钙粘蛋白恢复血管稳态，增强血管稳定性。通过特异性靶向TNFSF15-VEGF轴，L009提供了一种独特的治疗方法，将其与传统的抗vegf疗法区分开来。其抗血管生成和促进血管稳定性的双重作用突出了其作为新一代CNV治疗的潜力。进一步研究其长期疗效和与现有疗法协同作用的潜力是必要的。

{"title":"L009 peptide as a novel antiangiogenic agent for corneal neovascularization via regulation of the TNFSF15-VEGF axis","authors":"Ke Yan , Yiran Yang , Yi Han , Yuhan Zhang , Tong Zhou , Wenxin Sun , Ruochen Wang , Zhaolin Liu , Qinghe Zhang , Linfangzi Zhu , Meidi Tan , Caihong Huang , Jiaoyue Hu , Qiuping Liu , Zhaoqiang Zhang , Zuguo Liu","doi":"10.1016/j.jtos.2025.08.008","DOIUrl":"10.1016/j.jtos.2025.08.008","url":null,"abstract":"<div><div>Corneal neovascularization (CNV) is a leading cause of vision impairment, with existing therapeutic options offering limited efficacy. This study presents L009, a novel antiangiogenic agent derived from the Kringle 5 domain of human plasminogen, specifically a heptapeptide, designed to treat CNV. In preclinical models, L009 demonstrated substantial efficacy by markedly inhibiting endothelial cell proliferation and migration, reducing vascular permeability, and maintaining ocular safety. Mechanistically, L009 exerts its effects by upregulating tumor necrosis factor superfamily member 15 (TNFSF15), downregulating vascular endothelial growth factor receptor 2 (VEGFR2), and increasing the expression of soluble VEGFR1. These actions restore vascular homeostasis and enhance vascular stability through the upregulation of the tight junction protein VE-cadherin. By specifically targeting the TNFSF15-VEGF axis, L009 offers a distinctive therapeutic approach, differentiating it from conventional anti-VEGF therapies. Its dual action of anti-angiogenesis and promotion of vascular stability highlights its potential as a next-generation treatment for CNV. Further investigation into its long-term efficacy and potential for synergy with existing therapies is warranted.</div></div>","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":"38 ","pages":"Pages 274-289"},"PeriodicalIF":5.6,"publicationDate":"2025-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144914097","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

Two models of the structures of the lamellae in human meibum and the tear film lipid layer, TFLL 人体膜层和泪膜脂层的两种结构模型。

IF 5.6 1区医学 Q1 OPHTHALMOLOGY

Ocular Surface

Pub Date : 2025-08-21 DOI: 10.1016/j.jtos.2025.08.006

P. Ewen King-Smith , Carolyn G. Begley , Richard J. Braun

Two models of meibum and the TFLL are proposed. The first model is based on a reanalysis of x-ray studies which show the predominance of 11 nm thick lamellae above 30 °C, but below 30 °C, 5 nm thick lamellae predominate. By analogy to skin lipid, we denote these the long (LPP) and short period phase (SPP), respectively. In the model, the SPP lamellae are interdigitated bilayers of cholesteryl esters (CEs) oriented towards one surface and wax esters (WEs) oriented towards the other surface, with the long interdigitated CE and WE chains tilted. These lamellae are stacked with the same polarity, e.g., CE surface uppermost. At ocular surface temperature, the polarity of alternate layers is reversed, forming the LPP. This doubles the periodicity, but the tilt of the LPP long chains is reduced to render the periodicity more than twice the SPP. The model is consistent with changes in meibum near 30 °C found in calorimetry, viscoelasticity, infrared spectra, birefringence, reflectance, and high resolution images of meibum spread on saline. A secondary model explains the finding that most long saturated chains in CEs and WEs are branched. We propose a ‘bump and hollow’ model where a ‘bump’ is a branch on a WE chain fitting into a ‘hollow’, the linking oxygen atom in a neighboring CE chain; likewise, a bump on a CE chain fits a hollow on a WE chain. We aim to stimulate further development of lipid layer models, including the role of other molecules, to aid understanding of dry eye disease (DED).

提出了两种模型，分别是meibum模型和tfl模型。第一个模型是基于x射线研究的再分析，该研究表明，在30℃以上，11 nm厚的片层占主导地位，但在30℃以下，5 nm厚的片层占主导地位。与皮肤脂质类似，我们将它们分别称为长周期（LPP）和短周期（SPP）。在该模型中，SPP片层是面向一个表面的胆甾醇酯（CEs）和面向另一个表面的蜡酯（WEs）的交错双分子层，长交错的CE和WE链倾斜。这些片层以相同的极性堆叠，例如CE表面最上层。在眼表温度下，交替层的极性颠倒，形成LPP。该模型与热量法、粘弹性、红外光谱、双折射、反射率和高分辨率盐水中mebum分布的图像中发现的30℃附近mebum的变化一致。第二个模型解释了ce和WEs中大多数长饱和链是分支的这一发现。我们提出了一个“凹凸和空心”模型，其中“凹凸”是We链上的一个分支，与相邻CE链上的连接氧原子“空心”相吻合；同样，CE链上的凸起与WE链上的空洞相吻合。我们的目标是刺激脂质层模型的进一步发展，包括其他分子的作用，以帮助理解干眼病（DED）。

{"title":"Two models of the structures of the lamellae in human meibum and the tear film lipid layer, TFLL","authors":"P. Ewen King-Smith , Carolyn G. Begley , Richard J. Braun","doi":"10.1016/j.jtos.2025.08.006","DOIUrl":"10.1016/j.jtos.2025.08.006","url":null,"abstract":"<div><div>Two models of meibum and the TFLL are proposed. The first model is based on a reanalysis of x-ray studies which show the predominance of 11 nm thick lamellae above 30 °C, but below 30 °C, 5 nm thick lamellae predominate. By analogy to skin lipid, we denote these the long (LPP) and short period phase (SPP), respectively. In the model, the SPP lamellae are interdigitated bilayers of cholesteryl esters (CEs) oriented towards one surface and wax esters (WEs) oriented towards the other surface, with the long interdigitated CE and WE chains tilted. These lamellae are stacked with the same polarity, e.g., CE surface uppermost. At ocular surface temperature, the polarity of alternate layers is reversed, forming the LPP. This doubles the periodicity, but the tilt of the LPP long chains is reduced to render the periodicity more than twice the SPP. The model is consistent with changes in meibum near 30 °C found in calorimetry, viscoelasticity, infrared spectra, birefringence, reflectance, and high resolution images of meibum spread on saline. A secondary model explains the finding that most long saturated chains in CEs and WEs are branched. We propose a ‘bump and hollow’ model where a ‘bump’ is a branch on a WE chain fitting into a ‘hollow’, the linking oxygen atom in a neighboring CE chain; likewise, a bump on a CE chain fits a hollow on a WE chain. We aim to stimulate further development of lipid layer models, including the role of other molecules, to aid understanding of dry eye disease (DED).</div></div>","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":"38 ","pages":"Pages 251-259"},"PeriodicalIF":5.6,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144899255","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

IVCM image analysis for limbal stem cell deficiency: quantitative diagnostics of the corneal epithelium post-transplant recovery 角膜缘干细胞缺乏的IVCM图像分析：角膜上皮移植后恢复的定量诊断

IF 5.6 1区医学 Q1 OPHTHALMOLOGY

Ocular Surface

Pub Date : 2025-08-20 DOI: 10.1016/j.jtos.2025.08.005

Patrick Parkinson , Irina Makarenko , Oliver J. Baylis , Gustavo S. Figueiredo , Majlinda Lako , Anvar Shukurov , Francisco C. Figueiredo , Laura E. Wadkin

Purpose

Limbal stem cell deficiency (LSCD), a sight-threatening condition, is caused by dysfunction of the limbal stem cells (LSCs) which maintain the corneal epithelium. An effective treatment of LSCD is the transplantation of ex-vivo cultured LSCs from the patient's healthy other eye (in unilateral cases) or a donor eye (in bilateral cases) to the affected eye. Here we identify and quantify diagnostic and monitoring criteria for the recovery of the corneal epithelium post-LSC transplant using cellular images.

Methods

We consider the in-vivo confocal microscopy (IVCM) images from 10 patients with total unilateral LSCD caused by chemical burns, taken before and after LSC transplant. Images encompass the entire thickness of the corneal epithelium in the central and four peripheral regions. Approximately 1500 images were segmented using a bespoke algorithm to extract morphological data for analysis.

Results

The probability density of cell areas is shown to be a sensitive monitoring tool of corneal epithelial status. After a successful operation the distribution of cell areas is rather flat, reflecting an anomalously wide range of cell areas. As the cornea recovers, the distribution narrows with high statistical confidence and approaches that of the healthy cornea. We find a strong patient-to-patient variability in the epithelial cell area distribution and its variation with corneal depth. The corneal epithelial cell shape is independent of the cornea status despite a widespread expectation that healthy cells are roughly hexagonal.

Conclusion

Cell area is a sensitive and easily accessible marker of corneal epithelial recovery in LSCD patients post-LSC transplant.

角膜缘干细胞缺乏症（LSCD）是由维持角膜上皮的角膜缘干细胞（LSCs）功能障碍引起的一种视力威胁疾病。LSCD的一种有效治疗方法是将离体培养的LSCs从患者健康的另一只眼（单侧病例）或供体眼（双侧病例）移植到受影响的眼睛。在这里，我们使用细胞图像确定和量化lsc移植后角膜上皮恢复的诊断和监测标准。

{"title":"IVCM image analysis for limbal stem cell deficiency: quantitative diagnostics of the corneal epithelium post-transplant recovery","authors":"Patrick Parkinson , Irina Makarenko , Oliver J. Baylis , Gustavo S. Figueiredo , Majlinda Lako , Anvar Shukurov , Francisco C. Figueiredo , Laura E. Wadkin","doi":"10.1016/j.jtos.2025.08.005","DOIUrl":"10.1016/j.jtos.2025.08.005","url":null,"abstract":"<div><h3>Purpose</h3><div>Limbal stem cell deficiency (LSCD), a sight-threatening condition, is caused by dysfunction of the limbal stem cells (LSCs) which maintain the corneal epithelium. An effective treatment of LSCD is the transplantation of <em>ex-vivo</em> cultured LSCs from the patient's healthy other eye (in unilateral cases) or a donor eye (in bilateral cases) to the affected eye. Here we identify and quantify diagnostic and monitoring criteria for the recovery of the corneal epithelium post-LSC transplant using cellular images.</div></div><div><h3>Methods</h3><div>We consider the <em>in-vivo</em> confocal microscopy (IVCM) images from 10 patients with total unilateral LSCD caused by chemical burns, taken before and after LSC transplant. Images encompass the entire thickness of the corneal epithelium in the central and four peripheral regions. Approximately 1500 images were segmented using a bespoke algorithm to extract morphological data for analysis.</div></div><div><h3>Results</h3><div>The probability density of cell areas is shown to be a sensitive monitoring tool of corneal epithelial status. After a successful operation the distribution of cell areas is rather flat, reflecting an anomalously wide range of cell areas. As the cornea recovers, the distribution narrows with high statistical confidence and approaches that of the healthy cornea. We find a strong patient-to-patient variability in the epithelial cell area distribution and its variation with corneal depth. The corneal epithelial cell shape is independent of the cornea status despite a widespread expectation that healthy cells are roughly hexagonal.</div></div><div><h3>Conclusion</h3><div>Cell area is a sensitive and easily accessible marker of corneal epithelial recovery in LSCD patients post-LSC transplant.</div></div>","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":"38 ","pages":"Pages 266-273"},"PeriodicalIF":5.6,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144899294","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