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Corneal complications of Sjögren's disease: Insights from a large tertiary ophthalmological care center Sjögren病的角膜并发症:来自大型三级眼科护理中心的见解。
IF 5.6 1区 医学 Q1 OPHTHALMOLOGY Pub Date : 2025-11-28 DOI: 10.1016/j.jtos.2025.11.009
Gustavo Ortiz-Morales , Mauricio Muleiro-Alvarez , Eber A. Medina-Estrada , Guillermo Raúl Vera-Duarte , Nicolás Kahuam-López , Aida Jimenez-Corona , Alejandro Navas , Arturo Ramirez-Miranda , Esen K. Akpek , Enrique O. Graue-Hernandez

Purpose

To report the demographic characteristics, clinical spectrum, and outcomes of patients with extra-glandular corneal manifestations of Sjögren's disease (SjD).

Design

Retrospective review of electronic medical records.

Participants

Consecutive patients with SjD diagnosed per the 2016 American College of Rheumatology/European League Against Rheumatism criteria at a tertiary ophthalmology center.

Methods

Patients were systematically evaluated, diagnosed, and followed longitudinally. A database was generated by searching electronic records, collecting data on demographics, clinical and laboratory findings, treatments, and outcomes.

Main outcome measures

Prevalence and management of extra-glandular corneal manifestations of SjD.

Results

A total of 415 patients were included, mostly female (92.5 %), with a mean age of 63 years (range: 18–91) and a mean follow-up of 34 months (range: 1–120). Standalone SjD was present in 126 patients (30.28 %), and 289 (69.63 %) had associated autoimmune diseases, most commonly rheumatoid arthritis (n = 221) and systemic lupus erythematosus (n = 26). Diagnosis was based on ACR/EULAR score-based criteria (score ≥4) with positive serology (n = 372, 89.63 %) and positive minor salivary gland biopsy (n = 46, 11.08 %). Corneal complications were observed in 113 patients (27.2 %), including scarring (38/113), epithelial defects (22/113), and perforation. Corneal perforation occurred in 53 patients (12.77 %), most commonly at presentation (47/53, 88.67 %). Perforation rates were 5.56 % (7/126) in standalone SjD and 15.92 % (46/289) in SjD with other autoimmune diseases. At presentation, 56.6 % of patients with perforation (30/53) were not on systemic immunomodulatory treatment (IMT); they were subsequently treated. Six patients (11.32 %) developed perforation during follow-up while already on IMT and required escalation. All six had coexisting autoimmune diseases, primarily rheumatoid arthritis. To manage complications, 75 surgical procedures were performed, including keratoplasty. Five eyes were enucleated or eviscerated due to delayed presentation and infection.

Conclusions

Corneal complications, including perforation, are common in SjD and may occur even in the absence of other autoimmune diseases. Many patients present without systemic treatment. These findings support incorporating corneal manifestations into SjD disease activity indices to enable earlier medical intervention alongside surgical care.
目的报道Sjögren病(SjD)腺外角膜表现患者的人口学特征、临床谱和转归。设计:电子病历的回顾性分析。参与者:在三级眼科中心根据2016年美国风湿病学会/欧洲抗风湿病联盟标准诊断的连续SjD患者。方法对患者进行系统评估、诊断和纵向随访。通过搜索电子记录、收集人口统计、临床和实验室结果、治疗和结果等数据,建立了一个数据库。主要观察指标:SjD的腺外角膜表现的诊断和治疗。结果共纳入415例患者,女性居多(92.5%),平均年龄63岁(18 ~ 91岁),平均随访时间34个月(1 ~ 120个月)。126例(30.28%)患者存在独立的SjD, 289例(69.63%)患者存在相关自身免疫性疾病,最常见的是类风湿性关节炎(n = 221)和系统性红斑狼疮(n = 26)。诊断基于ACR/EULAR评分标准(评分≥4),血清学阳性(n = 372, 89.63%)和小唾液腺活检阳性(n = 46, 11.08%)。113例(27.2%)患者出现角膜并发症,包括瘢痕(38/113)、上皮缺损(22/113)和穿孔。53例(12.77%)患者发生角膜穿孔,最常见于就诊时(47/53,88.67%)。单发SjD的穿孔率为5.56%(7/126),合并其他自身免疫性疾病的SjD的穿孔率为15.92%(46/289)。在就诊时,56.6%的穿孔患者(30/53)未接受全身免疫调节治疗(IMT);他们随后接受了治疗。6名患者(11.32%)在随访期间出现穿孔,而已经进行了IMT并需要升级。这6人都同时患有自身免疫性疾病,主要是类风湿性关节炎。为了控制并发症,进行了75次手术,包括角膜移植术。由于延迟出现和感染,5只眼睛被去核或摘除。结论角膜并发症,包括穿孔,在SjD中很常见,即使没有其他自身免疫性疾病也可能发生。许多患者未接受全身治疗。这些发现支持将角膜表现纳入SjD疾病活动指数,以便在手术护理的同时进行早期医疗干预。
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引用次数: 0
Mechanistic insights into conjunctivalization in limbal stem cell deficiency using a lineage tracing approach 利用谱系追踪方法观察角膜缘干细胞缺乏症结合力的机制
IF 5.6 1区 医学 Q1 OPHTHALMOLOGY Pub Date : 2025-11-27 DOI: 10.1016/j.jtos.2025.11.011
Mijeong Park , Elvis Pandzic , John Males , Nick Di Girolamo

Purpose

Disease that develops on the ocular surface in animals and humans that have their limbal stem cells erased or their niche severely damaged by physical or chemical trauma, is difficult to visually evaluate in a progressive and long-term manner. When limbal stem cell deficiency (LSCD) develops under such circumstances, intravital clinical microscopy or other techniques cannot be used to accurately detail what transpires on the cornea. Here, we investigated the evolution of LSCD and characterize cellular transformations that arise when the limbal niche is lost.

Methods

We employed the multi-color K14CreERT2-Confetti transgenic reporter mice (n = 51) to monitor LSCD in real-time, combined with proliferation markers and in vitro analyses to identify and characterize conjunctival epithelial transformations using wild-type C57BL/6 mice (n = 31).

Results

Conjunctival epithelia either spawn MUC5AC + goblet cells (GCs) or K12+ cornea-like epithelia. These cells arise from Ki67+ proliferating differentiated conjunctival squames as opposed to DNA label retaining conjunctival stem/progenitor cells. In vitro analyses suggests that GC metaplasia (GCM) and conjunctival transdifferentiation (CjTD) evolve from environmental stress and soluble keratocyte elaborated signals and corneal matrix-associated physical cues.

Conclusions

GCM is a pathological process, as opposed to CjTD, which is the cornea's attempt to self-repair. The co-existence of two fundamentally diverse cellular interchanges establishes a medical conundrum in LSCD which may be resolved via pharmacological or biological intervention in conjunction with surgery to replenish the stem cell pool.
目的:当动物和人类的角膜缘干细胞被清除或其生态位因物理或化学创伤而严重受损时,在眼表发生的疾病很难以进行性和长期的方式进行视觉评估。当角膜缘干细胞缺乏症(LSCD)在这种情况下发生时,活体临床显微镜或其他技术无法准确地详细描述角膜上发生的事情。在这里,我们研究了LSCD的进化,并描述了当边缘生态位丢失时出现的细胞转化。方法采用多色K14CreERT2-Confetti转基因报告小鼠(n = 51)实时监测LSCD,并结合增殖标志物和体外分析鉴定野生型C57BL/6小鼠(n = 31)结膜上皮转化。结果结膜上皮可产生MUC5AC +杯状细胞(GCs)或K12+角膜样上皮。这些细胞来自Ki67+增殖分化的结膜鳞片,而不是保留DNA标记的结膜干细胞/祖细胞。体外分析表明,GC化生(GCM)和结膜转分化(CjTD)是由环境应激和可溶性角质细胞合成信号以及角膜基质相关的物理信号进化而来的。结论sgcm是一种病理过程,而CjTD是一种角膜自我修复的尝试。两种基本不同的细胞交换的共存建立了LSCD的医学难题,可以通过药物或生物干预结合手术来补充干细胞库来解决。
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引用次数: 0
Delphi panel on neuromodulation as a treatment strategy for dry eye disease: Unlocking the potential of natural tear production 德尔菲小组:神经调节作为干眼病的治疗策略:释放自然泪液产生的潜力
IF 5.6 1区 医学 Q1 OPHTHALMOLOGY Pub Date : 2025-11-27 DOI: 10.1016/j.jtos.2025.11.010
Esen Akpek , Lyndon Jones , Kelly K. Nichols , Lisa M. Nijm , Stephen Pflugfelder

Purpose

Chronic tear deficiency, through reduced production and/or increased evaporation, is regarded as a root cause of dry eye disease (DED). The goal of treating DED is restoration of the tear film ultimately resulting in ocular surface homeostasis. Multiple therapeutic prescription drugs to manage DED exist with varying speed of onset, overall magnitude of efficacy, and tolerability. Neuromodulation is an emerging treatment modality offering direct stimulation of natural tear production. A modified Delphi study was conducted to explore the role of neuromodulation as a treatment for DED.

Methods

Twenty DED experts participated in three rounds of structured electronic Delphi questionnaires. Consensus, defined as ≥ 80 %, was sought on 18 statements across three key DED topics: unmet treatment needs, the importance of natural tears in ocular surface homeostasis, and neuromodulation as a treatment approach. Statements were refined iteratively based on qualitative feedback and quantitative agreement from the panel.

Results

Consensus was reached on all 18 statements. Panelists affirmed that significant unmet needs persist in managing DED. Panelists agreed that stimulating patients’ natural tear production can help maintain and restore ocular surface homeostasis and that neuromodulation, through the ability to rapidly increase natural tear production, has the potential to effectively fill existing treatment gaps.

Conclusion

This Delphi panel reached consensus on the importance of restoring natural tear production as a primary goal in treating DED. Neuromodulation represents a promising treatment option for DED, offering a rapid and restorative therapeutic approach for natural tear production.
慢性泪液缺乏,通过减少生产和/或增加蒸发,被认为是干眼病(DED)的根本原因。治疗DED的目的是恢复泪膜,最终达到眼表稳态。多种治疗性处方药物治疗DED存在不同的发病速度,疗效的总体大小和耐受性。神经调节是一种新兴的治疗方式,提供直接刺激自然泪液的产生。我们进行了一项修正的德尔菲研究,以探讨神经调节作为DED治疗的作用。方法对20名DED专家进行三轮结构化电子德尔菲问卷调查。在三个关键DED主题(未满足的治疗需求、天然泪液在眼表稳态中的重要性和神经调节作为治疗方法)的18项陈述中寻求共识,定义为≥80%。根据小组的定性反馈和定量一致,对陈述进行了迭代改进。结果18项声明全部达成共识。小组成员确认,在管理DED方面仍然存在大量未满足的需求。小组成员一致认为,刺激患者的自然泪液分泌有助于维持和恢复眼表稳态,而神经调节通过快速增加自然泪液分泌的能力,有可能有效地填补现有的治疗空白。结论德尔菲小组一致认为恢复自然泪液生成是治疗DED的首要目标。神经调节是一种很有前途的治疗选择,为自然泪液的产生提供了快速和恢复性的治疗方法。
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引用次数: 0
Umbilical cord-derived mesenchymal stem cell therapy for acute Stevens Johnson syndrome/Toxic Epidermal Necrolysis with severe ocular involvement 脐带来源间充质干细胞治疗急性史蒂文斯·约翰逊综合征/中毒性表皮坏死松解伴严重眼部受累
IF 5.6 1区 医学 Q1 OPHTHALMOLOGY Pub Date : 2025-11-24 DOI: 10.1016/j.jtos.2025.11.006
Pier Luigi Surico , Chun-Bing Chen , Chuang-Wei Wang , Tai Ping Lee , Martin Sieber , Wen-Hung Chung , Kevin Sheng-Kai Ma , Yueh-Ju Tsai , Chi-Chin Sun , David Hui-Kang Ma
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引用次数: 0
Corneal sensitivity in dry eye disease: A systematic review 干眼病的角膜敏感性:一项系统综述
IF 5.6 1区 医学 Q1 OPHTHALMOLOGY Pub Date : 2025-11-12 DOI: 10.1016/j.jtos.2025.11.005
Emanuele Käser , Estelle Reymond , Daniela S. Nosch

Background

Dry eye disease (DED) is a worldwide prevalent condition; however, its pathophysiology is not well understood. Corneal nerves play a primary role in DED, and a better understanding of the changes to their morphology and function is required. This systematic review investigated changes to the function of corneal nerves.

Methods

Relevant literature from inception to September 10, 2025 was searched for in PubMed, Web of Science and Scopus, following the PRISMA statement. Studies measuring corneal sensitivity in patients with DED and in healthy controls were included. Publication selection and analysis were conducted independently by two authors.

Results

Twenty-five studies involving 1580 participants (1001 with DED and 579 healthy controls) were included. Nineteen studies used the Cochet-Bonnet aesthesiometer and found a consistently reduced corneal sensitivity in patients with DED. No consistent correlation was found between corneal sensitivity and DED severity, possibly due to heterogeneity of study design and methodology. Six studies used a variant of the Belmonte air jet aesthesiometer, reporting inconsistent results for mechanical corneal sensitivity. Increased sensitivity in DED patients was reported, using a stimulus at ambient temperature. One study used the Brill aesthesiometer and found reduced corneal sensitivity in DED patients.

Conclusion

Cochet-Bonnet measurements suggest a decreased mechanical corneal sensitivity in DED patients. Air jet aesthesiometry results were inconsistent, indicating variable responses from functionally different corneal nerve endings. Future research should employ reliable corneal sensitivity measurement methods with a wide stimulus range and standardised study designs to improve understanding of changes in corneal sensitivity in dry eye disease.
干眼病(DED)是一种世界性的常见病;然而,其病理生理机制尚不清楚。角膜神经在DED中起主要作用,需要更好地了解其形态和功能的变化。本系统综述研究了角膜神经功能的变化。方法按照PRISMA的声明,在PubMed、Web of Science和Scopus中检索成立至2025年9月10日的相关文献。研究测量了DED患者和健康对照的角膜敏感性。出版物选择和分析由两位作者独立进行。结果共纳入25项研究,共1580名受试者(1001名DED患者和579名健康对照)。19项研究使用Cochet-Bonnet美感计,发现DED患者的角膜敏感性持续降低。角膜敏感性和DED严重程度之间没有一致的相关性,可能是由于研究设计和方法的异质性。六项研究使用了贝尔蒙特喷气美感计的一种变体,报告了机械角膜敏感度不一致的结果。据报道,在环境温度下使用刺激会增加DED患者的敏感性。一项使用Brill美感计的研究发现,DED患者的角膜敏感度降低。结论cochet - bonnet测量提示DED患者角膜机械敏感性降低。喷气美感测量结果不一致,表明不同功能的角膜神经末梢的不同反应。未来的研究应采用可靠的角膜敏感性测量方法、广泛的刺激范围和标准化的研究设计,以提高对干眼病角膜敏感性变化的认识。
{"title":"Corneal sensitivity in dry eye disease: A systematic review","authors":"Emanuele Käser ,&nbsp;Estelle Reymond ,&nbsp;Daniela S. Nosch","doi":"10.1016/j.jtos.2025.11.005","DOIUrl":"10.1016/j.jtos.2025.11.005","url":null,"abstract":"<div><h3>Background</h3><div>Dry eye disease (DED) is a worldwide prevalent condition; however, its pathophysiology is not well understood. Corneal nerves play a primary role in DED, and a better understanding of the changes to their morphology and function is required. This systematic review investigated changes to the function of corneal nerves.</div></div><div><h3>Methods</h3><div>Relevant literature from inception to September 10, 2025 was searched for in PubMed, Web of Science and Scopus, following the PRISMA statement. Studies measuring corneal sensitivity in patients with DED and in healthy controls were included. Publication selection and analysis were conducted independently by two authors.</div></div><div><h3>Results</h3><div>Twenty-five studies involving 1580 participants (1001 with DED and 579 healthy controls) were included. Nineteen studies used the Cochet-Bonnet aesthesiometer and found a consistently reduced corneal sensitivity in patients with DED. No consistent correlation was found between corneal sensitivity and DED severity, possibly due to heterogeneity of study design and methodology. Six studies used a variant of the Belmonte air jet aesthesiometer, reporting inconsistent results for mechanical corneal sensitivity. Increased sensitivity in DED patients was reported, using a stimulus at ambient temperature. One study used the Brill aesthesiometer and found reduced corneal sensitivity in DED patients.</div></div><div><h3>Conclusion</h3><div>Cochet-Bonnet measurements suggest a decreased mechanical corneal sensitivity in DED patients. Air jet aesthesiometry results were inconsistent, indicating variable responses from functionally different corneal nerve endings. Future research should employ reliable corneal sensitivity measurement methods with a wide stimulus range and standardised study designs to improve understanding of changes in corneal sensitivity in dry eye disease.</div></div>","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":"39 ","pages":"Pages 1-16"},"PeriodicalIF":5.6,"publicationDate":"2025-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145509652","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
Repurposing schirmer strips for tear biomarker profiling using infrared spectroscopy 利用红外光谱法重新利用席默试纸进行眼泪生物标志物分析。
IF 5.6 1区 医学 Q1 OPHTHALMOLOGY Pub Date : 2025-10-01 DOI: 10.1016/j.jtos.2025.10.004
Haozhe Yu, Wenyu Wu, Jinji Cui, Yun Feng

Aims

To develop and validate a label-free analytical platform using attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy on Schirmer strips for tear biomarker profiling, and assess its diagnostic utility in differentiating aqueous-deficient dry eye disease (DED) subtypes.

Methods

Tear samples were collected using Schirmer strips from individuals undergoing routine ophthalmic examinations and from patients with aqueous-deficient DED, with or without primary Sjögren's syndrome. The wetted regions of the strips were analyzed using ATR-FTIR spectroscopy. Stepwise linear regression was employed to model the spectral contributions of individual proteins to the simulated tear spectrum. Spectral differences were quantified using Euclidean distances and correlated with biomarker concentrations and clinical parameters using Spearman correlation. Sparse partial least squares discriminant analysis (sPLS-DA) was then applied to classify DED subtypes.

Results

Prominent spectral features were observed in the 800-1700 cm−1 and ∼3000 cm−1 regions. Model fit for the simulated tear spectrum progressively improved with the sequential addition of protein spectra. Spectral Euclidean distance effectively captured the biomarker concentration gradient, as exemplified by lactoferrin. It demonstrated stronger correlations with tear film breakup time and lipid layer thickness than Schirmer wetting length and remained stable after elution. sPLS-DA accurately classified DED subtypes with an AUC of 0.963, driven primarily by protein-related spectral features.

Conclusions

The integrated tear analysis platform based on ATR-FTIR spectroscopy of Schirmer strips enables accurate, cost-effective differentiation of DED subtypes by capturing tear molecular fingerprints, laying the foundation for integrating tear-based precision medicine into routine clinical workflows.
目的:建立和验证Schirmer试纸上的衰减全反射-傅里叶变换红外(ATR-FTIR)光谱作为无标记泪液生物标志物分析的分析平台,并评估其在区分缺水型干眼病(DED)亚型中的诊断价值。方法:采用Schirmer试纸采集常规眼科检查个体和伴有或不伴有原发性Sjögren综合征的缺水性DED患者的泪液样本。用ATR-FTIR光谱分析了湿区。采用逐步线性回归来模拟单个蛋白质对模拟泪液光谱的光谱贡献。光谱差异通过欧几里得距离量化,并通过Spearman相关性与生物标志物浓度和临床参数相关。然后应用稀疏偏最小二乘判别分析(sPLS-DA)对DED亚型进行分类。结果:在800-1700 cm-1和~ 3000 cm-1区域观察到明显的光谱特征。单个蛋白质谱逐渐改善了模拟撕裂谱的拟合,在完整模型中达到最佳拟合。光谱欧几里得距离有效地捕获了生物标志物的浓度梯度,如乳铁蛋白。它与泪膜破裂时间和脂层厚度的相关性强于与润湿长度的相关性,且在洗脱后保持稳定。sPLS-DA对DED亚型进行准确分类,AUC为0.963,主要由蛋白质相关的光谱特征驱动。结论:基于Schirmer试纸ATR-FTIR光谱的泪液综合分析平台通过采集泪液分子指纹,实现了对DED亚型的准确、经济的鉴别,为泪液精准医学融入临床常规工作流程奠定了基础。
{"title":"Repurposing schirmer strips for tear biomarker profiling using infrared spectroscopy","authors":"Haozhe Yu,&nbsp;Wenyu Wu,&nbsp;Jinji Cui,&nbsp;Yun Feng","doi":"10.1016/j.jtos.2025.10.004","DOIUrl":"10.1016/j.jtos.2025.10.004","url":null,"abstract":"<div><h3>Aims</h3><div>To develop and validate a label-free analytical platform using attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy on Schirmer strips for tear biomarker profiling, and assess its diagnostic utility in differentiating aqueous-deficient dry eye disease (DED) subtypes.</div></div><div><h3>Methods</h3><div>Tear samples were collected using Schirmer strips from individuals undergoing routine ophthalmic examinations and from patients with aqueous-deficient DED, with or without primary Sjögren's syndrome. The wetted regions of the strips were analyzed using ATR-FTIR spectroscopy. Stepwise linear regression was employed to model the spectral contributions of individual proteins to the simulated tear spectrum. Spectral differences were quantified using Euclidean distances and correlated with biomarker concentrations and clinical parameters using Spearman correlation. Sparse partial least squares discriminant analysis (sPLS-DA) was then applied to classify DED subtypes.</div></div><div><h3>Results</h3><div>Prominent spectral features were observed in the 800-1700 cm<sup>−1</sup> and ∼3000 cm<sup>−1</sup> regions. Model fit for the simulated tear spectrum progressively improved with the sequential addition of protein spectra. Spectral Euclidean distance effectively captured the biomarker concentration gradient, as exemplified by lactoferrin. It demonstrated stronger correlations with tear film breakup time and lipid layer thickness than Schirmer wetting length and remained stable after elution. sPLS-DA accurately classified DED subtypes with an AUC of 0.963, driven primarily by protein-related spectral features.</div></div><div><h3>Conclusions</h3><div>The integrated tear analysis platform based on ATR-FTIR spectroscopy of Schirmer strips enables accurate, cost-effective differentiation of DED subtypes by capturing tear molecular fingerprints, laying the foundation for integrating tear-based precision medicine into routine clinical workflows.</div></div>","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":"38 ","pages":"Pages 330-336"},"PeriodicalIF":5.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145310447","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
Interdisciplinary management of belantamab mafodotin-associated ocular toxicity in clinical practice 贝兰他单-马夫多汀相关眼毒性的跨学科管理。
IF 5.6 1区 医学 Q1 OPHTHALMOLOGY Pub Date : 2025-10-01 DOI: 10.1016/j.jtos.2025.09.003
Mattan Arazi , Aya Wattad , Hila Magen , Abraham Avigdor , Nirit Agay , Yoav Berger , Irina S. Barequet

Purpose

Belantamab mafodotin (BLENREP), an antibody–drug conjugate for relapsed/refractory multiple myeloma (RRMM), is associated with corneal toxicity driven by limbal stem cell dysfunction and corneal epithelial damage. We examined how keratopathy severity relates to hematologic management decisions in clinical practice.

Methods

Retrospective cohort at a tertiary referral center, including RRMM patients treated with belantamab mafodotin (2019–2022). Ophthalmic examinations were performed at baseline and before each cycle; keratopathy was graded using the Keratopathy and Visual Acuity (KVA) scale. The primary outcome was the association between KVA severity (modeled as a time-dependent covariate) and management (dose reduction, treatment holiday, or discontinuation). Secondary outcomes included predictors of severe KVA, impact of management on immediate KVA change, and timing of the first management change.

Results

Among 41 patients (mean age 67.10 ± 11.78 years; 23/41 [56.1 %] female), 38/41 (92.68 %) developed KVA keratopathy. The median time to first KVA occurrence was 4.14 weeks, and to first management change was 7.29 weeks. Higher KVA grade was associated with earlier management change (HR 1.514; 95 % CI 1.048–2.187; p = 0.0270). At the first assessment after the initial intervention, KVA worsened after treatment holidays (+0.70 ± 0.114 grades) and improved after dose reductions (−0.20 ± 0.084; p = 0.0165). Overall, during follow-up, the most common intervention was a treatment holiday (23/37, 56.1 %), followed by dose reduction (16/37, 39.0 %) and discontinuation (6/37, 16.2 %).

Conclusion

KVA keratopathy occurred more frequently than in clinical trials, and nearly all patients required treatment modification. Given the strong relationship between KVA severity and management decisions, close ophthalmic monitoring from Grade 1 is warranted to mitigate progression and reduce vision-related morbidity.
目的:Belantamab mafodotin (BLENREP)是一种用于复发/难治性多发性骨髓瘤(RRMM)的抗体-药物偶联物,与角膜缘干细胞功能障碍和角膜上皮损伤驱动的角膜毒性相关。我们研究了在临床实践中角膜病变严重程度与血液学管理决策的关系。方法:在三级转诊中心进行回顾性队列研究,包括接受贝兰他单-马福多汀治疗的RRMM患者(2019-2022)。在基线和每个周期前进行眼科检查;使用角膜病变和视力(KVA)量表对角膜病变进行分级。主要结局是KVA严重程度(建模为时间相关协变量)与治疗(剂量减少、治疗期或停药)之间的关联。次要结局包括严重KVA的预测指标、管理对即刻KVA变化的影响以及首次管理变更的时间。结果:41例患者中(平均年龄67.10±11.78岁,女性23/41(56.1%)),38/41(92.68%)发生KVA性角膜病变。到第一次KVA发生的中位时间为4.14周,到第一次管理层变更的中位时间为7.29周。较高的KVA等级与较早的管理变更相关(HR 1.514; 95% CI 1.048-2.187; p=0.0270)。在初始干预后的第一次评估中,KVA在治疗假期后恶化(+0.70±0.114级),在剂量减少后改善(-0.20±0.084;p=0.0165)。总体而言,在随访期间,最常见的干预措施是治疗假期(23/ 37,56.1%),其次是减少剂量(16/ 37,39.0%)和停药(6/ 37,16.2%)。结论:KVA角膜病变的发生率高于临床试验,几乎所有患者都需要修改治疗方案。鉴于KVA严重程度与治疗决策之间的密切关系,从1级开始密切的眼科监测是有必要的,以减缓进展和减少视力相关的发病率。
{"title":"Interdisciplinary management of belantamab mafodotin-associated ocular toxicity in clinical practice","authors":"Mattan Arazi ,&nbsp;Aya Wattad ,&nbsp;Hila Magen ,&nbsp;Abraham Avigdor ,&nbsp;Nirit Agay ,&nbsp;Yoav Berger ,&nbsp;Irina S. Barequet","doi":"10.1016/j.jtos.2025.09.003","DOIUrl":"10.1016/j.jtos.2025.09.003","url":null,"abstract":"<div><h3>Purpose</h3><div>Belantamab mafodotin (BLENREP), an antibody–drug conjugate for relapsed/refractory multiple myeloma (RRMM), is associated with corneal toxicity driven by limbal stem cell dysfunction and corneal epithelial damage. We examined how keratopathy severity relates to hematologic management decisions in clinical practice.</div></div><div><h3>Methods</h3><div>Retrospective cohort at a tertiary referral center, including RRMM patients treated with belantamab mafodotin (2019–2022). Ophthalmic examinations were performed at baseline and before each cycle; keratopathy was graded using the Keratopathy and Visual Acuity (KVA) scale. The primary outcome was the association between KVA severity (modeled as a time-dependent covariate) and management (dose reduction, treatment holiday, or discontinuation). Secondary outcomes included predictors of severe KVA, impact of management on immediate KVA change, and timing of the first management change.</div></div><div><h3>Results</h3><div>Among 41 patients (mean age 67.10 ± 11.78 years; 23/41 [56.1 %] female), 38/41 (92.68 %) developed KVA keratopathy. The median time to first KVA occurrence was 4.14 weeks, and to first management change was 7.29 weeks. Higher KVA grade was associated with earlier management change (HR 1.514; 95 % CI 1.048–2.187; p = 0.0270). At the first assessment after the initial intervention, KVA worsened after treatment holidays (+0.70 ± 0.114 grades) and improved after dose reductions (−0.20 ± 0.084; p = 0.0165). Overall, during follow-up, the most common intervention was a treatment holiday (23/37, 56.1 %), followed by dose reduction (16/37, 39.0 %) and discontinuation (6/37, 16.2 %).</div></div><div><h3>Conclusion</h3><div>KVA keratopathy occurred more frequently than in clinical trials, and nearly all patients required treatment modification. Given the strong relationship between KVA severity and management decisions, close ophthalmic monitoring from Grade 1 is warranted to mitigate progression and reduce vision-related morbidity.</div></div>","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":"38 ","pages":"Pages 324-329"},"PeriodicalIF":5.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145226465","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
Recurrent retroprosthetic membranes in Boston Keratoprosthesis Type I: Incidence, risk factors, and complications 波士顿I型角膜移植术后复发性假体后膜:发病率、危险因素和并发症
IF 5.6 1区 医学 Q1 OPHTHALMOLOGY Pub Date : 2025-10-01 DOI: 10.1016/j.jtos.2025.11.002
Katherine G. Chen , Taylor W. Starnes , Sasha Kravets , Shanta Ghosh , Jose de la Cruz , Maria S. Cortina

Purpose

To identify pre-operative surgical factors associated with recurrent retroprosthetic membranes (RPMs) after Boston Keratoprosthesis (KPro) implantation, and to compare outcomes of patients with recurrent RPMs to those who had single or no RPM formation.

Methods

A single-center, retrospective study of all patients who underwent Boston Type I KPro implantation between 2006 and 2017 was performed. Patients with less than 1 year follow-up after device implantation were excluded. Patients were divided into 3 groups – no RPM, single RPM, and recurrent RPM. Recurrent RPM was defined as ≥2 visually significant RPM during follow-up. Statistical analysis was performed to assess factors associated with RPM status. Primary outcome measures included best-corrected visual acuity at 1 year and the need for RPM-related surgeries.

Results

109 of 148 KPro patients met the inclusion criteria. 45 % of patients had no RPM, 36.7 % had a single RPM, and 18.3 % had recurrent RPMs. At 1-year follow-up, visual acuity was decreased in both the recurrent (LogMAR 1.6) and single RPM (LogMar 1.18) groups compared to eyes with no RPM (LogMar 0.94). Eyes with recurrent RPM also required a significantly higher proportion of RPM-related surgery (p < 0.001). Eyes without prior penetrating keratoplasty (p = 0.04), pre-operative aniridia (p = 0.01), and post-operative occurrence of retinal detachments (p < 0.001) and corneal melts (p < 0.001) were found to be statistically significantly associated with RPM status.

Conclusions

Retroprosthetic membranes, especially when recurrent, play an important role in the secondary complications, visual outcomes, and device retention after KPro implantation.
目的探讨波士顿角膜假体(KPro)植入术后与复发性假体后膜(RPM)相关的术前因素,并比较复发性RPM患者与单一或无RPM形成患者的预后。方法采用单中心回顾性研究方法,对2006 - 2017年所有接受波士顿I型KPro植入术的患者进行分析。排除植入器械后随访时间少于1年的患者。患者分为无RPM、单次RPM和复发RPM 3组。复发性RPM定义为随访期间视觉显著性RPM≥2。统计分析评估与RPM状态相关的因素。主要结果测量包括1年最佳矫正视力和rpm相关手术的需要。结果148例KPro患者中有109例符合纳入标准。45%的患者无RPM, 36.7%的患者有单一RPM, 18.3%的患者有复发性RPM。在1年的随访中,与无RPM组(LogMAR 0.94)相比,复发组(LogMAR 1.6)和单RPM组(LogMAR 1.18)的视力均下降。反复出现RPM的眼睛也需要更高比例的RPM相关手术(p < 0.001)。未做过穿透性角膜移植术的眼睛(p = 0.04)、术前无虹膜(p = 0.01)、术后视网膜脱离(p < 0.001)和角膜融化(p < 0.001)的发生与RPM状态有统计学意义。结论假体后膜对KPro植入术后的继发性并发症、视觉效果和器械保留率起着重要的作用,尤其是在复发时。
{"title":"Recurrent retroprosthetic membranes in Boston Keratoprosthesis Type I: Incidence, risk factors, and complications","authors":"Katherine G. Chen ,&nbsp;Taylor W. Starnes ,&nbsp;Sasha Kravets ,&nbsp;Shanta Ghosh ,&nbsp;Jose de la Cruz ,&nbsp;Maria S. Cortina","doi":"10.1016/j.jtos.2025.11.002","DOIUrl":"10.1016/j.jtos.2025.11.002","url":null,"abstract":"<div><h3>Purpose</h3><div>To identify pre-operative surgical factors associated with recurrent retroprosthetic membranes (RPMs) after Boston Keratoprosthesis (KPro) implantation, and to compare outcomes of patients with recurrent RPMs to those who had single or no RPM formation.</div></div><div><h3>Methods</h3><div>A single-center, retrospective study of all patients who underwent Boston Type I KPro implantation between 2006 and 2017 was performed. Patients with less than 1 year follow-up after device implantation were excluded. Patients were divided into 3 groups – no RPM, single RPM, and recurrent RPM. Recurrent RPM was defined as ≥2 visually significant RPM during follow-up. Statistical analysis was performed to assess factors associated with RPM status. Primary outcome measures included best-corrected visual acuity at 1 year and the need for RPM-related surgeries.</div></div><div><h3>Results</h3><div>109 of 148 KPro patients met the inclusion criteria. 45 % of patients had no RPM, 36.7 % had a single RPM, and 18.3 % had recurrent RPMs. At 1-year follow-up, visual acuity was decreased in both the recurrent (LogMAR 1.6) and single RPM (LogMar 1.18) groups compared to eyes with no RPM (LogMar 0.94). Eyes with recurrent RPM also required a significantly higher proportion of RPM-related surgery (p &lt; 0.001). Eyes without prior penetrating keratoplasty (p = 0.04), pre-operative aniridia (p = 0.01), and post-operative occurrence of retinal detachments (p &lt; 0.001) and corneal melts (p &lt; 0.001) were found to be statistically significantly associated with RPM status.</div></div><div><h3>Conclusions</h3><div>Retroprosthetic membranes, especially when recurrent, play an important role in the secondary complications, visual outcomes, and device retention after KPro implantation.</div></div>","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":"38 ","pages":"Pages 424-430"},"PeriodicalIF":5.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145509653","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
Recanalization of lacrimal punctum after cauterization for severe dry eyes: Evidence for punctal progenitor cells 重度干眼烧灼后泪点再通:泪点祖细胞的证据
IF 5.6 1区 医学 Q1 OPHTHALMOLOGY Pub Date : 2025-10-01 DOI: 10.1016/j.jtos.2025.11.001
Sumer Doctor , Vidhi Anklesaria , Swati Singh
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引用次数: 0
Readership awareness series – Paper 9: Retraction of a publication 读者意识系列 - 文件 9:撤回出版物
IF 5.6 1区 医学 Q1 OPHTHALMOLOGY Pub Date : 2025-10-01 DOI: 10.1016/j.jtos.2024.01.008
Mohammad Javed Ali (Editor-in-Chief), Ali Djalilian (Former Editor-in-Chief)
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Ocular Surface
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