Clinical and Experimental Ophthalmology最新文献_第8页

Unveiling Endothelial Cell Expression Profiles in FEVR: Identification of Key Genes Associated With Pathological Neovascularisation in a FZD4M105V Mouse Model 揭示内皮细胞在FEVR中的表达谱：在FZD4M105V小鼠模型中鉴定与病理性新生血管相关的关键基因

IF 5.6 2区医学 Q1 OPHTHALMOLOGY

Clinical and Experimental Ophthalmology

Pub Date : 2025-10-16 DOI: 10.1111/ceo.70011

Huijuan Xu, Yunqi He, Xianjun Zhu, Rulian Zhao, Lin Zhang, Zhenglin Yang

Background

Familial exudative vitreoretinopathy (FEVR) is a disorder of retinal blood vessel development characterised by impaired retinal angiogenesis. While FZD4 mutations are established genetic causes of FEVR, the molecular mechanisms underlying pathological neovascularisation remain poorly understood.

Methods

CRISPR/Cas9 was used to generate the Fzd4^M105V mouse model. Comprehensive vascular phenotyping entailed retinal wholemount imaging, analysis of hyaloid vessel regression and immunohistochemical evaluation of the deep retinal vasculature. Flow cytometry sorting and single-cell RNA sequencing (scRNA-seq) were used to characterise the expression profiles of retinal endothelial cells (ECs) in mice.

Results

The FZD4^M105V model recapitulated key FEVR features including retinal aneurysmal vessels in adult mice, developmental abnormalities in juveniles, impaired deep vascular formation, delayed hyaloid regression, vascular leakage and reduced endothelial proliferation. ScRNA-seq revealed distinct transcriptional profiles in pathological EC clusters and tip cells. KEGG analysis revealed that the EC clusters were enriched in focal adhesion, Rap1, PI3K-Akt and apelin signalling pathways, whereas tip cells were enriched in the VEGF, chemokine, NF-κB and TNF signalling pathways. We further identified four novel candidate markers of pathological neovascularisation: Ctss, Ccl4, Ccl3 and Apoe. Subsequent validation confirmed the upregulation of CTSS and CCL4 within neovascular lesions, supporting their functional role in pathological angiogenesis.

Conclusions

We established a novel mouse model of pathological neovascularisation with a missense mutation and elucidated the expression profiles of retinal ECs. The identified pathways and novel biomarkers-particularly CTSS and CCL4-provide new insights for further pathogenesis investigation of FEVR.

背景：家族性渗出性玻璃体视网膜病变（FEVR）是一种以视网膜血管生成受损为特征的视网膜血管发育障碍。虽然FZD4突变是确定的FEVR的遗传原因，但病理性新生血管的分子机制仍然知之甚少。方法：采用CRISPR/Cas9技术建立Fzd4M105V小鼠模型。综合血管表型包括视网膜整体成像，玻璃状血管退化分析和视网膜深部血管的免疫组织化学评估。流式细胞术分选和单细胞RNA测序（scRNA-seq）用于表征小鼠视网膜内皮细胞（ECs）的表达谱。结果：FZD4M105V模型重现了FEVR的主要特征，包括成年小鼠视网膜动脉瘤血管、幼年小鼠发育异常、深部血管形成受损、透明体退化延迟、血管渗漏和内皮细胞增殖减少。ScRNA-seq显示病理EC簇和尖端细胞中不同的转录谱。KEGG分析显示，EC细胞簇富集于局灶黏附、Rap1、PI3K-Akt和apelin信号通路，而尖端细胞则富集于VEGF、趋化因子、NF-κB和TNF信号通路。我们进一步确定了病理性新生血管的四种新的候选标志物：Ctss、Ccl4、Ccl3和Apoe。随后的验证证实了CTSS和CCL4在新生血管病变中的上调，支持了它们在病理性血管生成中的功能作用。结论：我们建立了一种具有错义突变的小鼠病理性新生血管模型，并阐明了视网膜内皮细胞的表达谱。所确定的途径和新的生物标志物，特别是CTSS和ccl4，为进一步研究出血热的发病机制提供了新的见解。

{"title":"Unveiling Endothelial Cell Expression Profiles in FEVR: Identification of Key Genes Associated With Pathological Neovascularisation in a FZD4M105V Mouse Model","authors":"Huijuan Xu, Yunqi He, Xianjun Zhu, Rulian Zhao, Lin Zhang, Zhenglin Yang","doi":"10.1111/ceo.70011","DOIUrl":"10.1111/ceo.70011","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Familial exudative vitreoretinopathy (FEVR) is a disorder of retinal blood vessel development characterised by impaired retinal angiogenesis. While <i>FZD4</i> mutations are established genetic causes of FEVR, the molecular mechanisms underlying pathological neovascularisation remain poorly understood.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>CRISPR/Cas9 was used to generate the <i>Fzd4</i><sup><i>M105V</i></sup> mouse model. Comprehensive vascular phenotyping entailed retinal wholemount imaging, analysis of hyaloid vessel regression and immunohistochemical evaluation of the deep retinal vasculature. Flow cytometry sorting and single-cell RNA sequencing (scRNA-seq) were used to characterise the expression profiles of retinal endothelial cells (ECs) in mice.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The <i>FZD4</i><sup><i>M105V</i></sup> model recapitulated key FEVR features including retinal aneurysmal vessels in adult mice, developmental abnormalities in juveniles, impaired deep vascular formation, delayed hyaloid regression, vascular leakage and reduced endothelial proliferation. ScRNA-seq revealed distinct transcriptional profiles in pathological EC clusters and tip cells. KEGG analysis revealed that the EC clusters were enriched in focal adhesion, Rap1, PI3K-Akt and apelin signalling pathways, whereas tip cells were enriched in the VEGF, chemokine, NF-κB and TNF signalling pathways. We further identified four novel candidate markers of pathological neovascularisation: <i>Ctss</i>, <i>Ccl4</i>, <i>Ccl3</i> and <i>Apoe.</i> Subsequent validation confirmed the upregulation of CTSS and CCL4 within neovascular lesions, supporting their functional role in pathological angiogenesis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>We established a novel mouse model of pathological neovascularisation with a missense mutation and elucidated the expression profiles of retinal ECs. The identified pathways and novel biomarkers-particularly CTSS and CCL4-provide new insights for further pathogenesis investigation of FEVR.</p>\u0000 </section>\u0000 </div>","PeriodicalId":55253,"journal":{"name":"Clinical and Experimental Ophthalmology","volume":"54 1","pages":"113-126"},"PeriodicalIF":5.6,"publicationDate":"2025-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145310088","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Continuing Professional Development 持续专业发展

IF 5.6 2区医学 Q1 OPHTHALMOLOGY

Clinical and Experimental Ophthalmology

Pub Date : 2025-10-13 DOI: 10.1111/ceo.14603

RANZCO Fellows can claim CPD points by reading the following two articles which appear in this issue, and answering the five questions. Half an hour is awarded for each set of five questions answered. Please remember to claim your points.

Answers to questions published in previous issue

RANZCO会员可以通过阅读本期出现的以下两篇文章并回答五个问题来获得CPD积分。每回答一组5个问题，奖励半小时。请记得提出你的观点。对前几期问题的回答

引用次数: 0

Real-World Adoption of Artificial Intelligence in Diabetic Retinopathy Screening: What Is the Current Status? 人工智能在糖尿病视网膜病变筛查中的实际应用：现状如何？

IF 5.6 2区医学 Q1 OPHTHALMOLOGY

Clinical and Experimental Ophthalmology

Pub Date : 2025-10-13 DOI: 10.1111/ceo.14605

Paul Nderitu, Pearse A. Keane

<p>The prevalence of diabetes is projected to reach 783 million individuals by 2045 [<span>1</span>]. This rise will inevitably lead to a substantial increase in the prevalence of diabetic retinopathy (DR), which affects ~30% to 40% of people with diabetes and progresses to sight-threatening disease in 10% [<span>2</span>]. Timely screening reduces DR-related sight loss and has contributed to a decline in certifiable blindness in the United Kingdom, which has a national DR screening programme [<span>3</span>]. Despite the benefits of screening and the rising global burden of DR, an estimated 80% of people with diabetes worldwide lack access to regular screening [<span>2</span>]. This gap is particularly pronounced in low and middle-income countries (LMICs), where resource constraints and personnel shortages hinder the establishment and maintenance of effective DR screening programmes [<span>2</span>].</p><p>Artificial intelligence (AI) has emerged as a promising tool for automating DR grading, offering the potential to efficiently scale DR screening and alleviate a reliance on human graders. IDx-DR (Luminetics Core) was the first autonomous AI system in medicine to receive Food and Drug Administration (FDA) authorisation in 2018 for more-than-mild DR detection [<span>4</span>]. Deep learning-based AI systems have consistently demonstrated high diagnostic accuracy for referable DR detection in numerous retrospective and prospective validation studies [<span>4</span>]. AI systems are continually advancing, with Daley et al., in this issue of <i>Clinical and Experimental Ophthalmology</i> (CEO), describing the development of a dual-modality system which uses fundus photographs and optical coherence tomography scans [<span>5</span>]. In addition to accuracy, AI systems have demonstrated cost-effectiveness, enhanced clinical workflow efficiency and improved screening completion rates [<span>6, 7</span>]. Reflecting this progress, a recent review identified multiple approved AI systems for DR detection in the United States (3), European Union (21), United Kingdom (7) and Australia (8), collectively representing over half of all approved ophthalmic image analysis AI systems [<span>8</span>]. However, despite these regulatory achievements and promising validation data, the implementation of AI in clinical settings remains limited relative to the vast at-risk population.</p><p>In the United States, FDA-approved AI systems for DR screening have been deployed in primary care and diagnostic centres, with billing records indicating over 15 000 uses between 2018 and 2021 [<span>9</span>]. Deployment has predominantly occurred in higher-income urban areas associated with academic institutions [<span>9</span>]. The growth of AI-based DR screening in the United States has been modest, increasing by 1% between 2021 and 2023 compared to 185% for traditional fundus imaging used for DR screening in the same period [<span>10</span>].</p><p>In Singapore, the SELENA+ AI

到2045年，糖尿病患病率预计将达到7.83亿人。这种上升将不可避免地导致糖尿病视网膜病变（DR）患病率的大幅增加，糖尿病患者的患病率约为30%至40%，并在10%的糖尿病患者中发展为视力威胁疾病。及时筛查可减少DR相关的视力丧失，并有助于英国可证明失明的下降，英国有一个全国性DR筛查规划b[3]。尽管筛查有诸多好处，而且DR的全球负担也在不断增加，但据估计，全世界80%的糖尿病患者无法获得定期筛查。这一差距在低收入和中等收入国家尤为明显，在这些国家，资源限制和人员短缺阻碍了有效的DR筛查规划的建立和维持。人工智能（AI）已经成为自动化DR评分的一个很有前途的工具，它提供了有效扩展DR筛选和减轻对人工评分者依赖的潜力。IDx-DR （Luminetics Core）是2018年获得美国食品和药物管理局（FDA）授权用于轻度以上DR检测的首个医学自主人工智能系统。在众多回顾性和前瞻性验证研究中，基于深度学习的人工智能系统一直显示出可参考的DR检测的高诊断准确性[10]。人工智能系统正在不断发展，Daley等人在本期的《临床与实验眼科学》（CEO）中描述了一种双模系统的发展，该系统使用眼底照片和光学相干断层扫描[5]。除了准确性外，人工智能系统还证明了成本效益，提高了临床工作流程效率，提高了筛查完成率[6,7]。最近的一项审查反映了这一进展，在美国(3)、欧盟（21）、英国(7)和澳大利亚(8)确定了多个已批准用于DR检测的人工智能系统，占所有已批准的眼科图像分析人工智能系统的一半以上。然而，尽管取得了这些监管成就和有希望的验证数据，但相对于庞大的高危人群，人工智能在临床环境中的实施仍然有限。在美国，fda批准的用于DR筛查的人工智能系统已部署在初级保健和诊断中心，账单记录显示，2018年至2021年期间使用了超过1.5万次。部署主要发生在与学术机构相关的高收入城市地区。在美国，基于人工智能的DR筛查增长缓慢，在2021年至2023年期间增长了1%，而同期用于DR筛查的传统眼底成像增长了185%。在新加坡，SELENA+人工智能系统已被纳入国家DR筛查规划，这是首次将基于深度学习的人工智能系统部署到国家常规筛查计划中。整合过程包括监管审批、成本效益评估以及将该系统嵌入临床工作流程[10]。最近的一项现实世界前瞻性验证研究表明，该系统检测可参考DR[11]的操作灵敏度为94.7%，特异性为82.2%。在印度和泰国进行了大规模的视网膜疾病自动评估（ARDA）系统（b谷歌/Verily）试点实施，总共包括60多万次视网膜疾病筛查b[12]。令人鼓舞的是，人工智能系统的前瞻性评估正在农村和服务不足的人群中进行，如土著社区和中低收入国家，那里的需求最大[4,5,13,14]。自2011年以来，自动视网膜图像分析工具已在苏格兰、英国（iGraderM）和葡萄牙（RetMarker）的DR筛查项目中使用，RetMarker使人类评分员的负担减少了48.4%。虽然不是基于深度学习，但这些系统表明，从长远来看，自动分级可以安全有效地纳入DR筛查计划[10]。Tran等人最近发表在本期《CEO》上的一项范围审查确定了2018年至2023年期间在临床DR筛查中进行的18项人工智能系统实施研究。该研究确定了影响人工智能在DR筛查领域实施的若干障碍（如培训、基础设施和成本）和推动因素（如效率、可及性和结果）。因此，尽管迄今为止取得了可喜的进展，但为满足全球迅速上升的DR患病率所需的大规模人工智能采用仍面临挑战。人工智能系统必须无缝集成到临床工作流程中，以实现其临床效用。早期的经验（如谷歌在泰国初级保健诊所的ARDA试点部署）表明，如果临床工作流程中断，即使是高性能的人工智能系统也可能失败。

{"title":"Real-World Adoption of Artificial Intelligence in Diabetic Retinopathy Screening: What Is the Current Status?","authors":"Paul Nderitu, Pearse A. Keane","doi":"10.1111/ceo.14605","DOIUrl":"https://doi.org/10.1111/ceo.14605","url":null,"abstract":"<p>The prevalence of diabetes is projected to reach 783 million individuals by 2045 [<span>1</span>]. This rise will inevitably lead to a substantial increase in the prevalence of diabetic retinopathy (DR), which affects ~30% to 40% of people with diabetes and progresses to sight-threatening disease in 10% [<span>2</span>]. Timely screening reduces DR-related sight loss and has contributed to a decline in certifiable blindness in the United Kingdom, which has a national DR screening programme [<span>3</span>]. Despite the benefits of screening and the rising global burden of DR, an estimated 80% of people with diabetes worldwide lack access to regular screening [<span>2</span>]. This gap is particularly pronounced in low and middle-income countries (LMICs), where resource constraints and personnel shortages hinder the establishment and maintenance of effective DR screening programmes [<span>2</span>].</p><p>Artificial intelligence (AI) has emerged as a promising tool for automating DR grading, offering the potential to efficiently scale DR screening and alleviate a reliance on human graders. IDx-DR (Luminetics Core) was the first autonomous AI system in medicine to receive Food and Drug Administration (FDA) authorisation in 2018 for more-than-mild DR detection [<span>4</span>]. Deep learning-based AI systems have consistently demonstrated high diagnostic accuracy for referable DR detection in numerous retrospective and prospective validation studies [<span>4</span>]. AI systems are continually advancing, with Daley et al., in this issue of <i>Clinical and Experimental Ophthalmology</i> (CEO), describing the development of a dual-modality system which uses fundus photographs and optical coherence tomography scans [<span>5</span>]. In addition to accuracy, AI systems have demonstrated cost-effectiveness, enhanced clinical workflow efficiency and improved screening completion rates [<span>6, 7</span>]. Reflecting this progress, a recent review identified multiple approved AI systems for DR detection in the United States (3), European Union (21), United Kingdom (7) and Australia (8), collectively representing over half of all approved ophthalmic image analysis AI systems [<span>8</span>]. However, despite these regulatory achievements and promising validation data, the implementation of AI in clinical settings remains limited relative to the vast at-risk population.</p><p>In the United States, FDA-approved AI systems for DR screening have been deployed in primary care and diagnostic centres, with billing records indicating over 15 000 uses between 2018 and 2021 [<span>9</span>]. Deployment has predominantly occurred in higher-income urban areas associated with academic institutions [<span>9</span>]. The growth of AI-based DR screening in the United States has been modest, increasing by 1% between 2021 and 2023 compared to 185% for traditional fundus imaging used for DR screening in the same period [<span>10</span>].</p><p>In Singapore, the SELENA+ AI","PeriodicalId":55253,"journal":{"name":"Clinical and Experimental Ophthalmology","volume":"53 7","pages":"741-743"},"PeriodicalIF":5.6,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ceo.14605","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145272975","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Inherited Retinal Disease or Age-Related Macular Degeneration: Predictive Value of Genetic Testing in Macular Disease With Atypical Atrophy 遗传性视网膜疾病或年龄相关性黄斑变性：基因检测在黄斑病变伴非典型萎缩中的预测价值

IF 5.6 2区医学 Q1 OPHTHALMOLOGY

Clinical and Experimental Ophthalmology

Pub Date : 2025-10-13 DOI: 10.1111/ceo.70008

Alexis Ceecee Britten-Jones, Fred K. Chen, Heather G. Mack, Maria Kolic, Janise Hermawan, Doron G. Hickey, Thomas L. Edwards, Lauren N. Ayton, Robyn H. Guymer, Carla J. Abbott

Background

Both age-related macular degeneration (AMD) and inherited retinal disease (IRD) can present with outer retinal atrophy at the macula. Distinguishing between IRD and geographic atrophy (GA) secondary to AMD is important for appropriate management, particularly as disease-specific treatments become available. This study investigates the utility of genetic testing for suspected IRDs in individuals with atypical macular atrophy.

Methods

Twenty-four participants aged over 50, presenting with macular atrophy atypical for AMD, underwent clinical assessments, multimodal retinal imaging and exome-based sequencing covering known IRD genes. Three retinal ophthalmologists reviewed genetic and clinical data to reach a consensus for the underlying cause of macular atrophy and identified a set of features that challenge an AMD diagnosis and suggest a higher likelihood of an IRD.

Results

The panel judged 58% of atypical atrophy cases as likely being an IRD. Of these suspected cases, 57% (33% of the entire cohort) received IRD genetic confirmation (PRPH2, ABCA4 or MT-TL1 [m.3243A>G]–related IRD). The remaining cases were classified as GA (29%) or did not reach consensus on the likely diagnosis (13%). Clinical features aiding in the differentiation of IRD from GA included symptom onset before age 50, family history, distinctive autofluorescence patterns (speckled, reticular or widespread), extensive atrophy and absence of subretinal drusen.

Conclusion

IRD genetic testing is valuable if a positive identification is achieved, but negative results neither rule out IRD nor confirm AMD. Limitations in our ability to robustly differentiate IRD-related atrophy from GA, especially in advanced lesions, need further research to improve diagnostic accuracy.

背景：老年性黄斑变性（AMD）和遗传性视网膜疾病（IRD）均可表现为黄斑外视网膜萎缩。区分IRD和继发于AMD的地理萎缩（GA）对于适当的管理很重要，特别是当疾病特异性治疗可用时。本研究探讨了基因检测在非典型黄斑萎缩患者中疑似IRDs的效用。方法：24名年龄在50岁以上的参与者，表现为AMD的非典型黄斑萎缩，接受了临床评估、多模态视网膜成像和基于外显子组的测序，包括已知的IRD基因。三位视网膜眼科医生回顾了遗传和临床数据，对黄斑萎缩的潜在原因达成了共识，并确定了一组挑战AMD诊断的特征，并表明IRD的可能性更高。结果：专家组判断58%的非典型萎缩病例可能是IRD。在这些疑似病例中，57%（占整个队列的33%）接受了IRD基因确认（PRPH2、ABCA4或MT-TL1 [m]）。> 3243 G)有关的IRD)。其余病例被归类为GA（29%）或对可能的诊断未达成共识（13%）。帮助鉴别视网膜视网膜病变与GA的临床特征包括50岁前的症状发作、家族史、独特的自身荧光模式（斑点状、网状或广泛分布）、广泛萎缩和无视网膜下结节。结论：如果获得阳性鉴定，IRD基因检测是有价值的，但阴性结果既不能排除IRD也不能确认AMD。我们区分ird相关萎缩与GA的能力有限，特别是在晚期病变中，需要进一步研究以提高诊断准确性。

{"title":"Inherited Retinal Disease or Age-Related Macular Degeneration: Predictive Value of Genetic Testing in Macular Disease With Atypical Atrophy","authors":"Alexis Ceecee Britten-Jones, Fred K. Chen, Heather G. Mack, Maria Kolic, Janise Hermawan, Doron G. Hickey, Thomas L. Edwards, Lauren N. Ayton, Robyn H. Guymer, Carla J. Abbott","doi":"10.1111/ceo.70008","DOIUrl":"10.1111/ceo.70008","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Both age-related macular degeneration (AMD) and inherited retinal disease (IRD) can present with outer retinal atrophy at the macula. Distinguishing between IRD and geographic atrophy (GA) secondary to AMD is important for appropriate management, particularly as disease-specific treatments become available. This study investigates the utility of genetic testing for suspected IRDs in individuals with atypical macular atrophy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Twenty-four participants aged over 50, presenting with macular atrophy atypical for AMD, underwent clinical assessments, multimodal retinal imaging and exome-based sequencing covering known IRD genes. Three retinal ophthalmologists reviewed genetic and clinical data to reach a consensus for the underlying cause of macular atrophy and identified a set of features that challenge an AMD diagnosis and suggest a higher likelihood of an IRD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The panel judged 58% of atypical atrophy cases as likely being an IRD. Of these suspected cases, 57% (33% of the entire cohort) received IRD genetic confirmation (<i>PRPH2</i>, <i>ABCA4 or MT-TL1</i> [m.3243A>G]–related IRD). The remaining cases were classified as GA (29%) or did not reach consensus on the likely diagnosis (13%). Clinical features aiding in the differentiation of IRD from GA included symptom onset before age 50, family history, distinctive autofluorescence patterns (speckled, reticular or widespread), extensive atrophy and absence of subretinal drusen.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>IRD genetic testing is valuable if a positive identification is achieved, but negative results neither rule out IRD nor confirm AMD. Limitations in our ability to robustly differentiate IRD-related atrophy from GA, especially in advanced lesions, need further research to improve diagnostic accuracy.</p>\u0000 </section>\u0000 </div>","PeriodicalId":55253,"journal":{"name":"Clinical and Experimental Ophthalmology","volume":"54 1","pages":"67-77"},"PeriodicalIF":5.6,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ceo.70008","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145287766","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A Chat About Peer Review 谈谈同行评议。

IF 5.6 2区医学 Q1 OPHTHALMOLOGY

Clinical and Experimental Ophthalmology

Pub Date : 2025-10-12 DOI: 10.1111/ceo.70007

Justine R. Smith, Syed B. Ali, Binoy Appukuttan, Stewart R. Lake

<p>In February 2025, we received the peer reviewer comments for our invited review of uveitis therapeutics, a major (25-published page) article that had taken our team of seven clinicians almost a year to write. We were enthusiastic about the work and looked forward to tough constructive criticism to make the article even better. Reading through the comments, we initially wondered whether the wrong critique had been sent: ‘The methods section is meticulously detailed, allowing for reproducibility and transparency’ and ‘The results are presented systematically, with precise graphical representations’; yet, our work was a narrative review, and there were no methods and results sections, and further, the article had multiple large tables but no figures. In addition, none of the suggested revisions were specific to uveitis treatment. We concluded that the peer review was generated by artificial intelligence (AI), specifically by a large language model (LLM). Publicly available Quillbot AI Detector software [<span>1</span>] confirmed our suspicion: 100% of the review was ‘AI-generated’ and 0% was ‘human-written’ (accessed 26/2/2025).</p><p>Artificial intelligence is embedded in our professional and personal lives, whether we are aware or not. <i>Clinical and Experimental Ophthalmology</i> has featured a number of current applications of AI in ophthalmology specifically: diagnosis and management of common and rare eye diseases [<span>2-4</span>], ophthalmic screening [<span>5, 6</span>] and administrative or regulatory processes [<span>7, 8</span>]. To imagine a future in which AI is not part of generating and disseminating knowledge is to bury one's head in the sand. On that basis, it is not unexpected that AI is being used in the preparation of manuscripts for publication. The peer-reviewed journals have rules around this: in the case of <i>Clinical and Experimental Ophthalmology</i>, ‘Manuscripts that have been prepared by or with the assistance of [AI] must transparently declare this and describe in detail both the extent of the assistance as well as the system specifications used in the description of the methodology’ [<span>9</span>]. In contrast, the use of LLM in peer review of manuscripts has received much less attention.</p><p>The listed authors wrote this editorial, but in the process, we sought LLM input on the topic at hand. We asked 3 chatbots—ChatGPT [<span>10</span>], Google Gemini [<span>11</span>] and Microsoft Copilot [<span>12</span>] (accessed 18/8/2025)—the following question: ‘What are the advantages and disadvantages of using AI tools for scientific peer review?’ The three chatbots provided lists of advantages and disadvantages, which summarised some of the key issues. All noted the positives of speed, objectivity (reducing reviewer bias, long recognised to be an issue), integrity checking, and language support. Two chatbots also alluded to reviewer intellectual support, one of the most controversial aspects of using LLMs, as di

在2025年2月，我们收到了同行评议对我们邀请的葡萄膜炎治疗的评论，这是一篇重要的（25页）文章，我们的7名临床医生团队花了将近一年的时间来撰写。我们对这项工作充满热情，并期待着严厉的建设性批评，使文章变得更好。通过阅读评论，我们最初怀疑是否发出了错误的评论：“方法部分非常详细，允许可重复性和透明度”和“结果系统地呈现，具有精确的图形表示”；然而，我们的工作是一个叙述性的回顾，没有方法和结果部分，而且，文章有多个大表格，但没有数字。此外，没有一个建议的修订是针对葡萄膜炎治疗的。我们得出结论，同行评议是由人工智能（AI），特别是由大型语言模型（LLM）生成的。公开的Quillbot AI检测器软件[1]证实了我们的怀疑：100%的评论是“人工智能生成的”，0%是“人工编写的”（26/2/2025）。不管我们是否意识到，人工智能已经融入了我们的职业和个人生活。《临床与实验眼科学》介绍了人工智能在眼科学中的一些当前应用，具体包括：常见和罕见眼病的诊断和管理[2-4]、眼科筛查[5,6]和行政或监管流程[7,8]。想象一个人工智能不再参与产生和传播知识的未来，就是把自己的头埋在沙子里。在此基础上，人工智能被用于编写供出版的手稿也就不足为奇了。同行评议期刊对此有规定：在《临床和实验眼科学》的案例中，“由[人工智能]编写或在[人工智能]帮助下编写的手稿必须透明地声明这一点，并详细描述帮助的程度以及方法描述中使用的系统规格”[9]。相比之下，在手稿的同行评审中使用法学硕士受到的关注要少得多。列出的作者撰写了这篇社论，但在此过程中，我们寻求法学硕士对手头主题的投入。我们询问了3个聊天机器人——chatgpt[10]、谷歌Gemini[11]和Microsoft Copilot[12]（访问时间为2025年8月18日）——以下问题：“使用人工智能工具进行科学同行评议的利弊是什么？”这三个聊天机器人列出了优缺点，总结了一些关键问题。所有人都注意到了速度、客观性（减少审稿人偏见，这是一个长期以来被认为是一个问题）、完整性检查和语言支持的积极方面。两个聊天机器人还提到了审稿人的智力支持，这是使用法学硕士最具争议的方面之一，如下所述。在负面方面，所有聊天机器人都发现缺乏专业知识（同行审稿人的主要期望），与培训相关的偏见，以及法学硕士如何得出结论的不可知的“黑匣子”问题。其中一个聊天机器人提到了“幻觉”，更恰当的说法是“捏造”，另外两个则指出了在未经作者或期刊许可的情况下与公共软件工具共享未发表信息的重要伦理和隐私问题。关于在手稿的同行评审中使用法学硕士，业内有强烈的意见。进化生物学家卡尔·伯格斯特罗姆和集体行为科学家约瑟夫·巴克-科尔曼在他们的《自然职业专栏》中发表了一篇充满激情的反驳文章，他们担心人类科学活动的退化和科学家技能的丧失。他们写道：“我们冒着用低级自动化取代人类熟练程度的风险，却没有意识到我们正在失去什么。”他们担心llm会“侵蚀”“人类科学活动的深度和复杂性”。生物医学数据科学家James Zou在《自然》杂志的社论中更为温和地提到了法学硕士在学术写作和同行评议中的应用浪潮。他的团队开发了一个聊天机器人，可以提供科学的同行评议，并将评议与人类提供的评议进行比较，结果显示，超过50%的作者认为来自法学硕士的评议具有科学价值。他希望看到“社区规范和资源……确保法学硕士使审稿人、编辑和作者受益，而不损害科学过程的完整性”[14]。法学硕士在同行评审过程中拥有专业知识的看法是一种错觉。事实上，法学硕士的产出并不区分事实与虚构。对于眼科领域的临床医生和非临床医生研究人员，我们必须承认，我们不是人工智能应用方面的专家，必须谨慎行事。《临床与实验眼科学》（Clinical and Experimental Ophthalmology）的出版商Wiley提供了在同行评审中使用人工智能的最佳实践指南。摘自这份材料的节选：“人工智能技术可以用来提高同行评审报告中书面反馈的质量。这种使用必须在提交同行评审报告时透明地声明。同行审稿人不应将稿件上传到AI Technology。正如威利所强调的那样，将作者的手稿加载到公共聊天机器人中是对保密和隐私的侵犯，进一步可能侵犯版权，这两者都有潜在的法律影响。至少，该杂志可能会对违反这一政策的同行评议人采取惩罚措施。从哲学的角度来看，评论提供了第一个阅读甚至为有影响力的研究做出贡献的特权；雇用法学硕士来审阅手稿，就会使这一特殊机会失去机会。此外，提交给聊天机器人的材料会用于训练法学硕士——如果这些材料存在致命缺陷，或者需要修改，那么就会对科学知识产生令人担忧的影响。很明显，同行审稿人在一系列问题上面临着不同的意见；我们建议站在作者的角度考虑问题。从作者的角度来看，llm生成的评论通常是通用的，并且在很大程度上是不相关的，没有提供建设性的信息来支持他们的工作的特定主题的改进。在整个医学领域，包括眼科，工作量持续增加。审阅手稿增加了一个人的工作量。然而，批评是研究人员工作的一部分；此外，它有助于我们的持续专业发展。随着眼科文献几乎呈指数级增长，审查要求也在增加，而不是减少。那么，审稿人如何利用人工智能技术来发挥自己的优势，同时又符合同行评审的需求和政策呢？组织行为科学家Dritjon Gruda在《自然》职业专栏上发表的一篇文章在这方面很有帮助：通过人工智能实现更快、更聪明的同行评议的三个步骤。“浏览、口述、修改”：他一边读论文，一边用语音转文本软件做笔记；他将听写的笔记输入离线LLM，进行英语检查并组织复习；他亲自润色文本。因此，输出的内容是他自己的，而法学硕士提供编辑支持——但总是在他的监督下。在向临床和实验眼科学提交审稿时，表明您已使用法学硕士学位来纠正语言并组织您的文档。引用格鲁达的话：“通过聚焦论文中最重要的部分，将高效的笔记与人工智能的语言能力相结合，我们可以给作者提供他们需要的反馈，而不会让自己精疲力竭。”然而，如果你根本没有时间完成同行评议，立即拒绝邀请，并期待在更方便的时间收到另一个邀请。同行评议的期刊可以采取措施来防范法学硕士产生的同行评议。为了在这个问题上教育他们的人类同行审稿人，临床和实验眼科可以在审稿人界面上放置一个链接，链接到Wiley最佳实践指南的相关部分。另一个简单的修复方法是在评审提交界面上添加一个复选框，要求同行评审人员指出是否在评审中使用了LLM，如果使用了，使用的是什么以及如何使用的。该杂志在Wiley的研究交流筛选平台中使用复杂的工具，可以筛选新提交的剽窃和生成式人工智能b[18]的使用。同样的工具也可以用于筛选同行评审。可以插入数字水印来检测LLM[19]的使用，因为仅基于文本的检测可以证明具有挑战性[20]。编辑需要认真对待作者对人工智能产生的同行评议的担忧。当同行审稿人似乎违反了这些政策时，就需要进行调查，其后果可能包括禁止审查和通知个人所在的学术机构。在任何调查中，认识到审稿人的回应权和正当程序是至关重要的，因为没有任何人工智能检测工具是完美的。编辑还必须支持那些作品在他们的监督下受到损害的作者。他们应该指导作者忽略法学硕士产生的审稿，并可能安排一个快速的重新审稿，也许是由他们的编辑委员会成员之一。将作者置于延长的同行评议过程中是不公

{"title":"A Chat About Peer Review","authors":"Justine R. Smith, Syed B. Ali, Binoy Appukuttan, Stewart R. Lake","doi":"10.1111/ceo.70007","DOIUrl":"10.1111/ceo.70007","url":null,"abstract":"<p>In February 2025, we received the peer reviewer comments for our invited review of uveitis therapeutics, a major (25-published page) article that had taken our team of seven clinicians almost a year to write. We were enthusiastic about the work and looked forward to tough constructive criticism to make the article even better. Reading through the comments, we initially wondered whether the wrong critique had been sent: ‘The methods section is meticulously detailed, allowing for reproducibility and transparency’ and ‘The results are presented systematically, with precise graphical representations’; yet, our work was a narrative review, and there were no methods and results sections, and further, the article had multiple large tables but no figures. In addition, none of the suggested revisions were specific to uveitis treatment. We concluded that the peer review was generated by artificial intelligence (AI), specifically by a large language model (LLM). Publicly available Quillbot AI Detector software [<span>1</span>] confirmed our suspicion: 100% of the review was ‘AI-generated’ and 0% was ‘human-written’ (accessed 26/2/2025).</p><p>Artificial intelligence is embedded in our professional and personal lives, whether we are aware or not. <i>Clinical and Experimental Ophthalmology</i> has featured a number of current applications of AI in ophthalmology specifically: diagnosis and management of common and rare eye diseases [<span>2-4</span>], ophthalmic screening [<span>5, 6</span>] and administrative or regulatory processes [<span>7, 8</span>]. To imagine a future in which AI is not part of generating and disseminating knowledge is to bury one's head in the sand. On that basis, it is not unexpected that AI is being used in the preparation of manuscripts for publication. The peer-reviewed journals have rules around this: in the case of <i>Clinical and Experimental Ophthalmology</i>, ‘Manuscripts that have been prepared by or with the assistance of [AI] must transparently declare this and describe in detail both the extent of the assistance as well as the system specifications used in the description of the methodology’ [<span>9</span>]. In contrast, the use of LLM in peer review of manuscripts has received much less attention.</p><p>The listed authors wrote this editorial, but in the process, we sought LLM input on the topic at hand. We asked 3 chatbots—ChatGPT [<span>10</span>], Google Gemini [<span>11</span>] and Microsoft Copilot [<span>12</span>] (accessed 18/8/2025)—the following question: ‘What are the advantages and disadvantages of using AI tools for scientific peer review?’ The three chatbots provided lists of advantages and disadvantages, which summarised some of the key issues. All noted the positives of speed, objectivity (reducing reviewer bias, long recognised to be an issue), integrity checking, and language support. Two chatbots also alluded to reviewer intellectual support, one of the most controversial aspects of using LLMs, as di","PeriodicalId":55253,"journal":{"name":"Clinical and Experimental Ophthalmology","volume":"53 8","pages":"897-899"},"PeriodicalIF":5.6,"publicationDate":"2025-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ceo.70007","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145281735","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Stromal Curvature, Power and Corneal-Stromal Curvature Ratios From a Hybrid AS-OCT in Eyes With Keratoconus 混合AS-OCT对圆锥角膜的间质曲率、功率和角膜-间质曲率比。

IF 5.6 2区医学 Q1 OPHTHALMOLOGY

Clinical and Experimental Ophthalmology

Pub Date : 2025-09-30 DOI: 10.1111/ceo.70001

Jascha A. Wendelstein, Annabella Ostermaier, Katrin Freller, Arianna Grendele, Giacomo Savini, Catarina Praefke Coutinho, Robert Herber, Nikolaus Luft, Stefan Kassumeh, Achim Langenbucher, Siegfried Priglinger

Background

To characterise stromal curvature and curvature ratios in keratoconus (KCN) using anterior segment OCT, and to evaluate the implications of using single-, two-, and three-surface refractive models for corneal power estimation in ectatic eyes.

Methods

Retrospective observational study. Anterior segment OCT measurements (MS-39, CSO) were analysed. Anterior, stromal, and posterior curvature radii were computed across five concentric zones (2.0–6.0 mm) using a floating best-fit sphere, and curvature ratios were subsequently derived: anterior-to-stromal (ASR), stromal-to-posterior (SPR), and anterior-to-posterior (APR). Corneal power was calculated using one-, two-, and three-surface models. KCN severity was classified according to the Belin ABC grading stage and ASR, SPR, and APR were stratified accordingly.

Results

Data from 944 keratoconic eyes were analysed. Peripheral zones (6.0 mm) exhibited reduced variability in curvature measurement compared to central zones (3.0 mm). Differences between simplified (one- and two-surface) and three-surface power models correlated moderately with increased APR and SPR values. ASR, SPR, and APR all increased progressively with advancing ABC grade.

Conclusion

In advanced keratoconus, three-surface modelling yields different corneal power estimates versus simplified models in KC; prospective outcome studies are needed to assess clinical impact. Stromal curvature and its derived ratios provide novel structural metrics that change with KCN severity. Curvature ratio increase —especially APR and SPR— reflects posterior steepening and anterior–posterior decoupling, with possible implications for staging and surgical planning.

背景：利用前段OCT表征圆锥角膜（KCN）的基质曲率和曲率比，并评估使用单面、二面和三面屈光模型估算膨大眼角膜度数的意义。方法：回顾性观察研究。前段OCT测量（MS-39， CSO）进行分析。使用浮动最佳拟合球体计算五个同心区（2.0-6.0 mm）的前、间质和后曲率半径，随后推导出曲率比：前-间质（ASR）、基质-后（SPR）和前后（APR）。使用一面、二面和三面模型计算角膜度数。根据Belin ABC分级阶段对KCN的严重程度进行分级，并据此对ASR、SPR、APR进行分层。结果：对944只角膜晶状体眼的资料进行分析。与中心区域（3.0 mm）相比，外围区域（6.0 mm）的曲率测量变异性降低。简化（一面和两面）和三面功率模型之间的差异与APR和SPR值的增加适度相关。ASR、SPR、APR均随ABC分级升高而逐渐升高。结论：在晚期圆锥角膜中，三面模型与KC简化模型的角膜功率估算值不同；需要前瞻性结局研究来评估临床影响。基质曲率及其衍生比率提供了随KCN严重程度变化的新型结构指标。曲率比增加——尤其是APR和SPR——反映了后路变陡和前后解耦，可能对分期和手术计划有影响。

{"title":"Stromal Curvature, Power and Corneal-Stromal Curvature Ratios From a Hybrid AS-OCT in Eyes With Keratoconus","authors":"Jascha A. Wendelstein, Annabella Ostermaier, Katrin Freller, Arianna Grendele, Giacomo Savini, Catarina Praefke Coutinho, Robert Herber, Nikolaus Luft, Stefan Kassumeh, Achim Langenbucher, Siegfried Priglinger","doi":"10.1111/ceo.70001","DOIUrl":"10.1111/ceo.70001","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>To characterise stromal curvature and curvature ratios in keratoconus (KCN) using anterior segment OCT, and to evaluate the implications of using single-, two-, and three-surface refractive models for corneal power estimation in ectatic eyes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Retrospective observational study. Anterior segment OCT measurements (MS-39, CSO) were analysed. Anterior, stromal, and posterior curvature radii were computed across five concentric zones (2.0–6.0 mm) using a floating best-fit sphere, and curvature ratios were subsequently derived: anterior-to-stromal (ASR), stromal-to-posterior (SPR), and anterior-to-posterior (APR). Corneal power was calculated using one-, two-, and three-surface models. KCN severity was classified according to the Belin ABC grading stage and ASR, SPR, and APR were stratified accordingly.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Data from 944 keratoconic eyes were analysed. Peripheral zones (6.0 mm) exhibited reduced variability in curvature measurement compared to central zones (3.0 mm). Differences between simplified (one- and two-surface) and three-surface power models correlated moderately with increased APR and SPR values. ASR, SPR, and APR all increased progressively with advancing ABC grade.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>In advanced keratoconus, three-surface modelling yields different corneal power estimates versus simplified models in KC; prospective outcome studies are needed to assess clinical impact. Stromal curvature and its derived ratios provide novel structural metrics that change with KCN severity. Curvature ratio increase —especially APR and SPR— reflects posterior steepening and anterior–posterior decoupling, with possible implications for staging and surgical planning.</p>\u0000 </section>\u0000 </div>","PeriodicalId":55253,"journal":{"name":"Clinical and Experimental Ophthalmology","volume":"54 1","pages":"9-20"},"PeriodicalIF":5.6,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ceo.70001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145193922","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The Long Journey of Treatment for Wet Macular Degeneration, Is It Worth It? 治疗湿性黄斑变性的漫漫征途，值得吗？

IF 5.6 2区医学 Q1 OPHTHALMOLOGY

Clinical and Experimental Ophthalmology

Pub Date : 2025-09-25 DOI: 10.1111/ceo.70004

Mark Gillies

<p>Randomised clinical trials (RCTs) do not provide the long-term data that are required to assess the overall efficacy of interventions for chronic conditions, such as neovascular age-related macular degeneration (nAMD), that may require ongoing treatment for up to 20 years. The MARINA and ANCHOR (ranibizumab) and VIEW (aflibercept) studies of vascular endothelial growth factor (VEGF) inhibitors only lasted 2 years [<span>1-3</span>]. Mean visual or treated eyes improved impressively in the first year, but it was already starting to decline by the end of the second year. Only observational studies can provide data beyond this point.</p><p>Early observational studies reported surprisingly poor outcomes. The SEVEN-UP study, a seven-year follow-up of eyes that had participated in the MARINA and ANCHOR trials of ranibizumab, and incorporated the 2-year HORIZON extension [<span>4</span>], reported that mean visual acuity (VA) had dropped 8.6 letters below the baseline value 7 years after starting treatment after improving by 11.2 letters at 2 years [<span>5</span>]. Macular atrophy was reported to have developed in 98% of treated eyes; in 90% it involved the foveal centre. Fortunately, this finding that all eyes eventually developed macular atrophy was anomalous; it has never been replicated. Persistent activity at the final visit was found in 68% of eyes, indicating the main problem appears to have been gross under-treatment, with an average of only 2 injections given per year for the last 3 years and 41% of eyes stopping treatment altogether. The European AURA study of eyes starting treatment in 2009 did not even find good short-term outcomes: it reported mean improvements in visual acuity of just +2.4 letters at 12 months and +0.6 letters at 24 months, after a mean of only 5.0 and 2.2 injections respectively, again indicating inadequate treatment [<span>6</span>]. It was starting to look like long-term treatment of nAMD with VEGF inhibitors was hardly worth it.</p><p>Outcomes reported around the same time by observational studies from Australia, where the drugs were fully reimbursed without restriction and practitioners generally employed proactive regimens from the start, were substantially better. One 7-year study from the Fight Retinal Blindness! project reported that the mean VA of eyes starting treatment between 2007 and 2010 improved by 6.3 letters after 6 months and remained above the mean presenting VA for around 6 years. Mean VA was 2.6 letters lower than baseline after 7 years. A median of 6 injections was given in the first year followed by 5 injections annually through 7 years. These outcomes demonstrated that reasonably good outcomes could be achieved with VEGF inhibitors for nAMD in real world practice if treatment were adequate [<span>7</span>].</p><p>This issue of <i>The Journal</i> includes a meta-analysis of studies that have reported 10-year outcomes of treatment of nAMD with VEGF inhibitors by Spooner et al. [<span>8</span>] Th

一项研究报道，如果患有nAMD的眼睛没有发生SRFI或MA bbb，接受VEGF抑制剂的眼睛在3年内保持了最初6个月的视力改善。因此，在开发出针对萎缩和纤维化的有效干预措施之前，我们可能看不到nAMD治疗结果的实质性改善。这项荟萃分析提供了来自不同来源的良好证据，表明VEGF抑制剂可以持续给予患者10年，并有合理的结果。当然，并不是所有的眼睛都会出现黄斑萎缩。平均VA下降了近2条线，但在对一些早期随机对照试验中未经治疗的对照组的数据分析中，VA下降了13条线，从而证实了治疗的一个非常实质性的好处，值得付款人的持续支持，并证明了患者经常繁重的治疗负担是合理的。指导抗视网膜失明治疗结果登记，包括湿性黄斑变性。他接受了Oche， Bayer， Apellis和Astellas的项目资助。他从这些公司的顾问委员会和演讲中获得酬金和旅行支持。

{"title":"The Long Journey of Treatment for Wet Macular Degeneration, Is It Worth It?","authors":"Mark Gillies","doi":"10.1111/ceo.70004","DOIUrl":"10.1111/ceo.70004","url":null,"abstract":"<p>Randomised clinical trials (RCTs) do not provide the long-term data that are required to assess the overall efficacy of interventions for chronic conditions, such as neovascular age-related macular degeneration (nAMD), that may require ongoing treatment for up to 20 years. The MARINA and ANCHOR (ranibizumab) and VIEW (aflibercept) studies of vascular endothelial growth factor (VEGF) inhibitors only lasted 2 years [<span>1-3</span>]. Mean visual or treated eyes improved impressively in the first year, but it was already starting to decline by the end of the second year. Only observational studies can provide data beyond this point.</p><p>Early observational studies reported surprisingly poor outcomes. The SEVEN-UP study, a seven-year follow-up of eyes that had participated in the MARINA and ANCHOR trials of ranibizumab, and incorporated the 2-year HORIZON extension [<span>4</span>], reported that mean visual acuity (VA) had dropped 8.6 letters below the baseline value 7 years after starting treatment after improving by 11.2 letters at 2 years [<span>5</span>]. Macular atrophy was reported to have developed in 98% of treated eyes; in 90% it involved the foveal centre. Fortunately, this finding that all eyes eventually developed macular atrophy was anomalous; it has never been replicated. Persistent activity at the final visit was found in 68% of eyes, indicating the main problem appears to have been gross under-treatment, with an average of only 2 injections given per year for the last 3 years and 41% of eyes stopping treatment altogether. The European AURA study of eyes starting treatment in 2009 did not even find good short-term outcomes: it reported mean improvements in visual acuity of just +2.4 letters at 12 months and +0.6 letters at 24 months, after a mean of only 5.0 and 2.2 injections respectively, again indicating inadequate treatment [<span>6</span>]. It was starting to look like long-term treatment of nAMD with VEGF inhibitors was hardly worth it.</p><p>Outcomes reported around the same time by observational studies from Australia, where the drugs were fully reimbursed without restriction and practitioners generally employed proactive regimens from the start, were substantially better. One 7-year study from the Fight Retinal Blindness! project reported that the mean VA of eyes starting treatment between 2007 and 2010 improved by 6.3 letters after 6 months and remained above the mean presenting VA for around 6 years. Mean VA was 2.6 letters lower than baseline after 7 years. A median of 6 injections was given in the first year followed by 5 injections annually through 7 years. These outcomes demonstrated that reasonably good outcomes could be achieved with VEGF inhibitors for nAMD in real world practice if treatment were adequate [<span>7</span>].</p><p>This issue of <i>The Journal</i> includes a meta-analysis of studies that have reported 10-year outcomes of treatment of nAMD with VEGF inhibitors by Spooner et al. [<span>8</span>] Th","PeriodicalId":55253,"journal":{"name":"Clinical and Experimental Ophthalmology","volume":"53 7","pages":"744-745"},"PeriodicalIF":5.6,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ceo.70004","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145139466","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Systemic Surveillance Guidelines for Uveal Melanoma: A Systematic Review 葡萄膜黑色素瘤的系统监测指南：系统综述。

IF 5.6 2区医学 Q1 OPHTHALMOLOGY

Clinical and Experimental Ophthalmology

Pub Date : 2025-09-24 DOI: 10.1111/ceo.70002

Farzana Y. Zaman, Aisha Ghaus, Mark Shackleton, Damien Kee, Anthony M. Joshua, Roderick O'Day, Malaka Ameratunga

Background

Uveal melanoma (UM) is the most common primary intraocular tumour. Despite effective local therapies, UM has a high risk of metastatic recurrence, most frequently to the liver. A significant proportion of patients treated definitively for primary UM eventually experience metastatic disease. Systemic surveillance to detect recurrence is critical to maximise therapeutic options. Whilst international guidelines exist, there are currently no standardised Australian guidelines for surveillance imaging. This systematic review examines the literature regarding systemic surveillance methods following local treatment for UM.

Methods

Medline, Embase and PubMed databases were searched, from 2010 to 01-07-2024, using keywords related to uveal melanoma and surveillance. Eligible studies were identified by two independent reviewers, and a systematic review was undertaken.

Results

Of 840 records, six guidelines and institutional consensus statements were identified, and an additional 13 studies were included. Most studies were cohort studies (n = 7), with the rest being case–control studies and reliability analyses. Risk stratification methods and surveillance strategies varied, with most studies recommending increased frequency (at least every 6 months) and higher-resolution imaging modalities (MRI over ultrasound) for higher-risk patients.

Conclusion

Despite several published guidelines, existing evidence regarding optimal surveillance strategies in localised primary UM is of variable quality, relying on cohort studies and limited by heterogeneity, as assessed by the modified Newcastle-Ottawa Scale. There is a clear need to further define local practices and outcomes to direct future guidelines.

背景：葡萄膜黑色素瘤（Uveal melanoma， UM）是最常见的原发性眼内肿瘤。尽管有效的局部治疗，UM有转移性复发的高风险，最常见的是肝脏。有相当比例的患者接受了明确的原发性UM治疗，最终会出现转移性疾病。系统监测以发现复发是最大化治疗选择的关键。虽然存在国际准则，但目前还没有标准化的澳大利亚监测成像准则。本系统综述研究了有关UM局部治疗后系统监测方法的文献。方法：检索Medline、Embase和PubMed数据库，检索时间为2010年1月7日至2024年7月1日，检索关键词为葡萄膜黑色素瘤和监测。符合条件的研究由两名独立审稿人确定，并进行系统评价。结果：在840份记录中，确定了6份指南和机构共识声明，并纳入了另外13项研究。大多数研究为队列研究（n = 7），其余为病例对照研究和可靠性分析。风险分层方法和监测策略各不相同，大多数研究建议对高风险患者增加检查频率（至少每6个月一次）和采用更高分辨率的成像方式（MRI over ultrasound）。结论：尽管有一些已发表的指南，但现有的关于局部原发性UM最佳监测策略的证据质量参差不齐，依赖于队列研究，并受到异质性的限制，通过修改的纽卡斯尔-渥太华量表进行评估。显然有必要进一步界定当地的做法和结果，以指导未来的指导方针。

{"title":"Systemic Surveillance Guidelines for Uveal Melanoma: A Systematic Review","authors":"Farzana Y. Zaman, Aisha Ghaus, Mark Shackleton, Damien Kee, Anthony M. Joshua, Roderick O'Day, Malaka Ameratunga","doi":"10.1111/ceo.70002","DOIUrl":"10.1111/ceo.70002","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Uveal melanoma (UM) is the most common primary intraocular tumour. Despite effective local therapies, UM has a high risk of metastatic recurrence, most frequently to the liver. A significant proportion of patients treated definitively for primary UM eventually experience metastatic disease. Systemic surveillance to detect recurrence is critical to maximise therapeutic options. Whilst international guidelines exist, there are currently no standardised Australian guidelines for surveillance imaging. This systematic review examines the literature regarding systemic surveillance methods following local treatment for UM.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Medline, Embase and PubMed databases were searched, from 2010 to 01-07-2024, using keywords related to uveal melanoma and surveillance. Eligible studies were identified by two independent reviewers, and a systematic review was undertaken.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Of 840 records, six guidelines and institutional consensus statements were identified, and an additional 13 studies were included. Most studies were cohort studies (<i>n</i> = 7), with the rest being case–control studies and reliability analyses. Risk stratification methods and surveillance strategies varied, with most studies recommending increased frequency (at least every 6 months) and higher-resolution imaging modalities (MRI over ultrasound) for higher-risk patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Despite several published guidelines, existing evidence regarding optimal surveillance strategies in localised primary UM is of variable quality, relying on cohort studies and limited by heterogeneity, as assessed by the modified Newcastle-Ottawa Scale. There is a clear need to further define local practices and outcomes to direct future guidelines.</p>\u0000 </section>\u0000 </div>","PeriodicalId":55253,"journal":{"name":"Clinical and Experimental Ophthalmology","volume":"54 1","pages":"99-112"},"PeriodicalIF":5.6,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ceo.70002","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145132855","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Ten-Year Incidence, Risk Factors and Progression Rate of Macular Atrophy in Neovascular Age-Related Macular Degeneration 新生血管性年龄相关性黄斑变性患者黄斑萎缩的十年发生率、危险因素及进展率。

IF 5.6 2区医学 Q1 OPHTHALMOLOGY

Clinical and Experimental Ophthalmology

Pub Date : 2025-09-19 DOI: 10.1111/ceo.14608

Francesco Romano, Marco Casaluci, Antonio Valastro, Matteo Airaldi, Paolo Milella, Francesco Pozzo Giuffrida, Elisa Cozzi, Andrea Aretti, Kelvin YC Teo, Chui Ming Gemmy Cheung, Marco Nassisi, Francesco Viola, Giovanni Staurenghi, Alessandro Invernizzi

Background

To evaluate the 10-year cumulative incidence, progression rates, and risk factors for macular atrophy (MA) in neovascular age-related macular degeneration (nAMD) patients receiving long-term anti-vascular endothelial growth factor (VEGF) therapy.

Methods

Retrospective, multicenter, cohort study including 148 eyes from 140 nAMD patients treated with a pro-re-nata (PRN) anti-VEGF regimen and followed for ≥ 10 years. Annual multimodal imaging—including blue autofluorescence [BAF], spectral-domain optical coherence tomography [SD-OCT] and near-infrared reflectance—was reviewed to detect and quantify MA using RegionFinder. Kaplan–Meier analysis estimated cumulative MA incidence, while mixed-effects Cox and linear regressions identified risk factors and progression rates.

Results

Baseline MA prevalence was 23.0%, increasing to 64.9% at 5 years and 79.8% at 10 years. Foveal involvement occurred in 47.4% of cases. Significant predictors for MA included baseline BCVA < 20/40 (HR = 1.50, p = 0.02), greater central subfield thickness (CST) fluctuations (HR = 1.04, p = 0.01), and more frequent submacular haemorrhages (HR = 1.34, p = 0.04). Type 3 macular neovascularization was associated with fovea-involving MA (HR = 2.03, p = 0.02). Mean MA size increased from 0.34 to 2.27 mm at 10 years, progressing at 0.20 mm/year (β = 0.15, p < 0.001). Eyes with incident MA exhibited faster progression (β = 0.03, p = 0.01) and worse BCVA decline compared to those with baseline MA (−1.96 vs. −1.42 letters/year, p < 0.001).

Conclusions

nAMD patients treated with PRN anti-VEGF therapy demonstrated a high 10-year cumulative incidence of MA (79.8%), with poor baseline BCVA and CST fluctuations as key risk factors. Eyes with incident MA progressed faster and were associated with greater visual decline, suggesting a more visually impactful atrophy.

背景：评估长期接受抗血管内皮生长因子（VEGF）治疗的新生血管性年龄相关性黄斑变性（nAMD）患者10年累积发病率、进展率和黄斑萎缩（MA）的危险因素。方法：回顾性、多中心、队列研究，包括140名接受PRN抗vegf方案治疗的nAMD患者的148只眼睛，随访≥10年。回顾了使用RegionFinder检测和量化MA的年度多模态成像技术，包括蓝色自身荧光（BAF）、光谱域光学相干层析成像（SD-OCT）和近红外反射。Kaplan-Meier分析估计累积MA发病率，而混合效应Cox和线性回归确定危险因素和进展率。结果：基线MA患病率为23.0%，5年增至64.9%，10年增至79.8%。47.4%的病例发生中央凹受累。结论：接受PRN抗vegf治疗的nAMD患者10年累积MA发病率高（79.8%），基线BCVA和CST波动差是关键危险因素。发生MA的眼睛进展更快，并伴有更大的视力下降，提示更严重的视觉影响性萎缩。

{"title":"Ten-Year Incidence, Risk Factors and Progression Rate of Macular Atrophy in Neovascular Age-Related Macular Degeneration","authors":"Francesco Romano, Marco Casaluci, Antonio Valastro, Matteo Airaldi, Paolo Milella, Francesco Pozzo Giuffrida, Elisa Cozzi, Andrea Aretti, Kelvin YC Teo, Chui Ming Gemmy Cheung, Marco Nassisi, Francesco Viola, Giovanni Staurenghi, Alessandro Invernizzi","doi":"10.1111/ceo.14608","DOIUrl":"10.1111/ceo.14608","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>To evaluate the 10-year cumulative incidence, progression rates, and risk factors for macular atrophy (MA) in neovascular age-related macular degeneration (nAMD) patients receiving long-term anti-vascular endothelial growth factor (VEGF) therapy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Retrospective, multicenter, cohort study including 148 eyes from 140 nAMD patients treated with a pro-re-nata (PRN) anti-VEGF regimen and followed for ≥ 10 years. Annual multimodal imaging—including blue autofluorescence [BAF], spectral-domain optical coherence tomography [SD-OCT] and near-infrared reflectance—was reviewed to detect and quantify MA using RegionFinder. Kaplan–Meier analysis estimated cumulative MA incidence, while mixed-effects Cox and linear regressions identified risk factors and progression rates.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Baseline MA prevalence was 23.0%, increasing to 64.9% at 5 years and 79.8% at 10 years. Foveal involvement occurred in 47.4% of cases. Significant predictors for MA included baseline BCVA < 20/40 (HR = 1.50, <i>p</i> = 0.02), greater central subfield thickness (CST) fluctuations (HR = 1.04, <i>p</i> = 0.01), and more frequent submacular haemorrhages (HR = 1.34, <i>p</i> = 0.04). Type 3 macular neovascularization was associated with fovea-involving MA (HR = 2.03, <i>p</i> = 0.02). Mean MA size increased from 0.34 to 2.27 mm at 10 years, progressing at 0.20 mm/year (<i>β</i> = 0.15, <i>p</i> < 0.001). Eyes with incident MA exhibited faster progression (<i>β</i> = 0.03, <i>p</i> = 0.01) and worse BCVA decline compared to those with baseline MA (−1.96 vs. −1.42 letters/year, <i>p</i> < 0.001).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>nAMD patients treated with PRN anti-VEGF therapy demonstrated a high 10-year cumulative incidence of MA (79.8%), with poor baseline BCVA and CST fluctuations as key risk factors. Eyes with incident MA progressed faster and were associated with greater visual decline, suggesting a more visually impactful atrophy.</p>\u0000 </section>\u0000 </div>","PeriodicalId":55253,"journal":{"name":"Clinical and Experimental Ophthalmology","volume":"54 1","pages":"55-66"},"PeriodicalIF":5.6,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ceo.14608","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145088472","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Deep Learning-Based Detection of Reticular Pseudodrusen in Age-Related Macular Degeneration 基于深度学习的老年性黄斑变性网状假性黄斑检测。

IF 5.6 2区医学 Q1 OPHTHALMOLOGY

Clinical and Experimental Ophthalmology

Pub Date : 2025-09-08 DOI: 10.1111/ceo.14607

Himeesh Kumar, Yelena Bagdasarova, Scott Song, Doron G. Hickey, Amy C. Cohn, Mali Okada, Robert P. Finger, Jan H. Terheyden, Ruth E. Hogg, Pierre-Henry Gabrielle, Louis Arnould, Maxime Jannaud, Xavier Hadoux, Peter van Wijngaarden, Carla J. Abbott, Lauren A. B. Hodgson, Roy Schwartz, Adnan Tufail, Emily Y. Chew, Cecilia S. Lee, Erica L. Fletcher, Melanie Bahlo, Brendan R. E. Ansell, Alice Pébay, Robyn H. Guymer, Aaron Y. Lee, Zhichao Wu

Background

Reticular pseudodrusen (RPD) signify a critical phenotype driving vision loss in age-related macular degeneration (AMD). This study sought to develop and externally test a deep learning (DL) model to detect RPD on optical coherence tomography (OCT) scans with expert-level performance.

Methods

RPD were manually segmented in 9800 OCT B-scans from individuals enrolled in a multicentre randomised trial. A DL model for instance segmentation of RPD was developed and evaluated against four retinal specialists in an internal test dataset. The primary outcome was the performance of the DL model for detecting RPD in OCT volumes in five external test datasets compared to two retinal specialists.

Results

In an internal test dataset consisting of 250 OCT B-scans, the DL model produced RPD segmentations that had higher agreement with four retinal specialists (Dice similarity coefficient [DSC] = 0.76) than the agreement amongst the specialists (DSC = 0.68; p < 0.001). In the five external test datasets consisting of 1017 eyes from 812 individuals, the DL model detected RPD in OCT volumes with a similar level of performance as two retinal specialists (area under the receiver operator characteristic curve [AUC] = 0.94, 0.95 and 0.96 respectively; p ≥ 0.32).

Conclusions

We present a DL model for automatic detection of RPD with expert-level performance, which could be used to support the clinical management of AMD. This model has been made publicly available to facilitate future research to understand this critical, yet enigmatic, AMD phenotype.

背景：网状假性黄斑变性（RPD）是导致年龄相关性黄斑变性（AMD）视力丧失的关键表型。本研究旨在开发并外部测试一种深度学习（DL）模型，以检测具有专家级性能的光学相干断层扫描（OCT）扫描上的RPD。方法：在一项多中心随机试验中，对9800名个体的OCT b扫描进行RPD手工分割。开发了一个用于RPD实例分割的DL模型，并在内部测试数据集中对四名视网膜专家进行了评估。主要结果是与两名视网膜专家相比，DL模型在五个外部测试数据集中检测OCT卷中的RPD的性能。结果：在由250个OCT b扫描组成的内部测试数据集中，DL模型产生的RPD分割与四位视网膜专家（Dice相似系数[DSC] = 0.76）的一致性高于专家之间的一致性（DSC = 0.68; p）。结论：我们提出了一个具有专家水平性能的RPD自动检测DL模型，可用于支持AMD的临床管理。该模型已公开提供，以促进未来的研究，以了解这一关键的，但神秘的，AMD表型。

{"title":"Deep Learning-Based Detection of Reticular Pseudodrusen in Age-Related Macular Degeneration","authors":"Himeesh Kumar, Yelena Bagdasarova, Scott Song, Doron G. Hickey, Amy C. Cohn, Mali Okada, Robert P. Finger, Jan H. Terheyden, Ruth E. Hogg, Pierre-Henry Gabrielle, Louis Arnould, Maxime Jannaud, Xavier Hadoux, Peter van Wijngaarden, Carla J. Abbott, Lauren A. B. Hodgson, Roy Schwartz, Adnan Tufail, Emily Y. Chew, Cecilia S. Lee, Erica L. Fletcher, Melanie Bahlo, Brendan R. E. Ansell, Alice Pébay, Robyn H. Guymer, Aaron Y. Lee, Zhichao Wu","doi":"10.1111/ceo.14607","DOIUrl":"10.1111/ceo.14607","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Reticular pseudodrusen (RPD) signify a critical phenotype driving vision loss in age-related macular degeneration (AMD). This study sought to develop and externally test a deep learning (DL) model to detect RPD on optical coherence tomography (OCT) scans with expert-level performance.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>RPD were manually segmented in 9800 OCT B-scans from individuals enrolled in a multicentre randomised trial. A DL model for instance segmentation of RPD was developed and evaluated against four retinal specialists in an internal test dataset. The primary outcome was the performance of the DL model for detecting RPD in OCT volumes in five external test datasets compared to two retinal specialists.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In an internal test dataset consisting of 250 OCT B-scans, the DL model produced RPD segmentations that had higher agreement with four retinal specialists (Dice similarity coefficient [DSC] = 0.76) than the agreement amongst the specialists (DSC = 0.68; <i>p</i> < 0.001). In the five external test datasets consisting of 1017 eyes from 812 individuals, the DL model detected RPD in OCT volumes with a similar level of performance as two retinal specialists (area under the receiver operator characteristic curve [AUC] = 0.94, 0.95 and 0.96 respectively; <i>p</i> ≥ 0.32).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>We present a DL model for automatic detection of RPD with expert-level performance, which could be used to support the clinical management of AMD. This model has been made publicly available to facilitate future research to understand this critical, yet enigmatic, AMD phenotype.</p>\u0000 </section>\u0000 </div>","PeriodicalId":55253,"journal":{"name":"Clinical and Experimental Ophthalmology","volume":"54 1","pages":"78-85"},"PeriodicalIF":5.6,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ceo.14607","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145024888","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0