Ocular Surface最新文献

英文中文

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

IF 5.6 1区医学 Q1 OPHTHALMOLOGY

Ocular Surface

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

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

Purpose

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

Methods

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

Results

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

Conclusion

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

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

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引用次数: 0

Economic burden of keratitis patients with inpatient care: a nationwide, multicenter registry study 住院治疗角膜炎患者的经济负担：一项全国性、多中心登记研究

IF 5.6 1区医学 Q1 OPHTHALMOLOGY

Ocular Surface

Pub Date : 2025-08-19 DOI: 10.1016/j.jtos.2025.08.007

He Xie , Hai Liu , Chenxi Wang , Kexin Tang , Qinxiang Zheng , Kaisheng Wang , Baihua Chen , He Dong , Feng Wen , Tao Sun , Jizhong Yang , Yanning Yang , Limin Chen , Zhirong Liu , Shaozhen Zhao , Wei Qiang , Qi Xie , Yuping Han , Linying Huang , Man Yu , Wei Chen

引用次数: 0

Pipeline: Patient, physician and developer view of drugs vs. devices 管道：患者、医生和开发人员对药物与设备的看法

IF 5.6 1区医学 Q1 OPHTHALMOLOGY

Ocular Surface

Pub Date : 2025-08-18 DOI: 10.1016/j.jtos.2025.08.004

Gary D. Novack

引用次数: 0

Clinical recommendations for the management of Pythium insidiosum keratitis 治疗藏皮角膜炎的临床建议

IF 5.6 1区医学 Q1 OPHTHALMOLOGY

Ocular Surface

Pub Date : 2025-08-18 DOI: 10.1016/j.jtos.2025.08.003

Bhupesh Bagga , Lakshminarayanan Gowtham , Ali R. Djalilian , Savitri Sharma

Pythium insidiosum has emerged as a challenging cause of keratitis in recent decades, due to its unique microbiological and clinical features, often is mistaken for fungal keratitis. Anti-fungal therapies have proven ineffective due to the organism's distinct cellular structure. Based on in vitro and in vivo models there has been a shift towards the use of antibacterial agents like linezolid and azithromycin, which have shown promising results. This concise review provides an update on the recommended diagnostic techniques and management strategies to assist clinicians in navigating this complex disease landscape.

近几十年来，由于其独特的微生物学和临床特征，二氧化钛已成为角膜炎的一个具有挑战性的原因，经常被误认为是真菌性角膜炎。抗真菌疗法已被证明无效，由于生物体的独特的细胞结构。在体外和体内模型的基础上，已经转向使用抗菌药物，如利奈唑胺和阿奇霉素，这些药物已经显示出有希望的结果。这篇简明的综述提供了最新的推荐诊断技术和管理策略，以帮助临床医生在这种复杂的疾病景观中导航。

引用次数: 0

Exploration of imaging and molecular biomarkers for differentiation of neuropathic corneal pain from dry eye syndrome 神经病变性角膜疼痛与干眼综合征鉴别的影像学及分子标志物探讨。

IF 5.6 1区医学 Q1 OPHTHALMOLOGY

Ocular Surface

Pub Date : 2025-08-14 DOI: 10.1016/j.jtos.2025.08.002

Jun Cheng , Chang Liu , Mingyi Yu , Isabelle Xin Yu Lee , Xinyue Wang , Victor Wei-Tse Hsu , Aya Takahashi , Jodhbir S. Mehta , Lei Zhou , Louis Tong , Yu-Chi Liu

Purpose

To investigate the imaging, clinical, and tear proteomic profiles between neuropathic corneal pain (NCP) and dry eye disease (DED), and to identify potential imaging and molecular biomarkers for the differentiation of NCP from DED.

Methods

This cross-sectional study included 54 NCP patients (105 eyes), 53 DED patients (106 eyes), and 54 healthy controls (108 eyes). All subjects were evaluated with ocular surface assessment, ocular pain assessment survey (OPAS), and in-vivo confocal microscopy to characterize corneal nerves, microneuromas (MNs), immune cells, and epithelial cells. Tear quantitative proteomics were analyzed.

Results

The percentage of presence of MNs, the number, total area, total perimeter, and average area of MNs were significantly higher in the NCP group than the other two groups. NCP patients had significantly higher corneal nerve fiber width. MNs parameters were significantly correlated with the OPAS scores (r = 0.20 to 0.48, all P < 0.05). Particularly, in peripheral NCP, both MNs total area and perimeter exhibited a significant correlation with the OPAS eye pain intensity (r = 0.55–0.57, both P < 0.05). Combinations of MNs parameters and OPAS scores had high diagnostic efficacy for NCP with an area under the curve (AUC) of 0.916. A total of 129 significantly differential proteins were identified, such as up-regulated vinculin and down-regulated DLG associated protein 4 in NCP, as well as up-regulated S100A12 and matrix metallopeptidase 9 in DED. These dysregulated proteins were linked to neuron apoptosis, inflammatory response, and synaptic transmission.

Conclusion

NCP patients present with different imaging features, clinical characteristics and proteomic profiles, compared with DED patients. These can be used as differentiating indicators.

目的：探讨神经性角膜疼痛（NCP）和干眼病（DED）的影像学、临床和泪液蛋白质组学特征，并寻找区分NCP和DED的潜在影像学和分子生物标志物。方法：本横断面研究纳入54例NCP患者（105眼）、53例DED患者（106眼）和54例健康对照（108眼）。通过眼表评估、眼痛评估调查（OPAS）和体内共聚焦显微镜对所有受试者进行评估，以表征角膜神经、微神经瘤（MNs）、免疫细胞和上皮细胞。泪液定量蛋白质组学分析。结果：NCP组MNs的出现率、数目、总面积、周长及平均面积均显著高于其他两组。NCP患者角膜神经纤维宽度明显增高。MNs参数与OPAS评分显著相关（r=0.20 ~ 0.48）。结论：与DED患者相比，NCP患者表现出不同的影像学特征、临床特征和蛋白质组学特征。这些可以用作区分指标。

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引用次数: 0

Differences in pre-surgical baseline tear proteome are associated with persistent post-refractive surgery pain 术前撕裂蛋白组基线差异与屈光术后持续疼痛有关。

IF 5.6 1区医学 Q1 OPHTHALMOLOGY

Ocular Surface

Pub Date : 2025-08-10 DOI: 10.1016/j.jtos.2025.08.001

Brooke M. Harkness , Siting Chen , Ashok P. Reddy , Kilsun Kim , Deborah M. Hegarty , Steven J. Everist , Julie A. Saugstad , Jodi Lapidus , Anat Galor , Sue A. Aicher

Purpose

Most patients who undergo refractive surgery have excellent outcomes, but a subset experience persistent eye pain after the procedure. We hypothesized that pre-operative tear fluid proteins are distinct in patients who develop pain after surgery.

Methods

Patients undergoing refractive surgery (LASIK or PRK) provided tear fluid samples and eye pain reports (numeric rating scale (NRS) 0–10) before (baseline) and after surgery. Patients reporting no baseline pain, but pain (NRS ≥3) at 3 months (Pain group, n = 31), were compared to patients with no pain before or 3 months after surgery (No Pain group, n = 47). Baseline samples were analyzed by tandem mass tag spectrometry. Proteins demonstrating differential expression based on fold change thresholds, area under the ROC curve (AUC), or feature importance in random forest classification were identified and used to construct multi-protein models.

Results

Thirty-nine proteins showed differential expression between Pain and No Pain patients. Multi-protein models showed that a subset of 4 proteins classified the Pain group with an AUC of 0.87 (95 % CI, 0.79–0.96). This model contained 2 proteins that increased (PGRC1 and PFD3) and 2 proteins that decreased (IBP3 and SPB9) in Pain patients, showing bi-directional, dynamic effects.

Conclusion

Analysis of pre-surgical tears reveals proteome differences in patients who go on to experience persistent pain 3 months after refractive surgery. Since these tear samples were taken prior to surgery, when patients were not experiencing pain, these protein patterns may inform the discovery of risk biomarkers for persistent post-refractive surgery eye pain.

目的：大多数接受屈光手术的患者都有很好的结果，但有一部分患者在手术后会经历持续的眼睛疼痛。我们假设术前泪液蛋白在术后出现疼痛的患者中是不同的。方法：接受屈光手术（LASIK或PRK）的患者在术前（基线）和术后提供泪液样本和眼部疼痛报告（数值评定量表（NRS） 0 - 10）。无基线疼痛，但3个月时疼痛（NRS bbbb3）的患者（疼痛组，n=31）与术前或术后3个月无疼痛的患者（无疼痛组，n=47）进行比较。基线样品采用串联质谱分析。基于折叠变化阈值、ROC曲线下面积（AUC）或随机森林分类中特征重要性的差异表达蛋白被识别并用于构建多蛋白模型。结果：39个蛋白在疼痛组和无疼痛组有差异表达。多蛋白模型显示，4种蛋白组成的子集将疼痛组分类，AUC为0.87 （95% CI, 0.79 - 0.96）。该模型在Pain患者中含有2种升高的蛋白（PGRC1和PFD3）和2种降低的蛋白（IBP3和SPB9），呈双向动态作用。结论：对术前撕裂的分析揭示了屈光手术后3个月持续疼痛患者的蛋白质组差异。由于这些泪液样本是在手术前采集的，当患者没有疼痛时，这些蛋白质模式可能有助于发现屈光手术后持续眼睛疼痛的风险生物标志物。

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引用次数: 0

Antibiotic resistance of Pseudomonas aeruginosa from ocular samples in Canada: a 25-year analysis 加拿大眼部样本中铜绿假单胞菌的抗生素耐药性：25年分析。

IF 5.6 1区医学 Q1 OPHTHALMOLOGY

Ocular Surface

Pub Date : 2025-07-30 DOI: 10.1016/j.jtos.2025.07.011

Alfonso Iovieno , Barbara Burgos-Blasco , Derek Chan , Sean Ling , Simon Holland , Sonia N. Yeung

Objective

To identify trends in antibiotic resistance patterns of Pseudomonas aeruginosa (PA) over a multi-decade period and analyse clinical outcomes.

Methods

PA isolates from ocular samples were collected over a 25-year time period in British Columbia, Canada. Source and antibiotic resistance were recorded. Demographic data, previous ocular history and clinical outcomes of patients with PA keratitis were analysed and compared in moxifloxacin-resistant versus moxifloxacin-sensitive PA keratitis cases.

Results

321 ocular isolates of Pseudomonas were identified, 297 (92.5 %) of which were PA (101, 34 % cornea samples). Resistance to chloramphenicol was 88.7 %, 23.7 % to moxifloxacin and 10.1 % to meropenem. An increase in moxifloxacin resistance and non-susceptibility was noted, with a decrease in tobramycin resistance. The same trend was not observed for other fluroquinolone antibiotics. 14 (4.7 %) PA isolates were multi drug-resistant. 53 PA corneal isolates were included in the clinical analysis: 21 (40 %) sensitive, 17 (32 %) intermediate and 15 (28 %) resistant to moxifloxacin. Non-susceptible PA patients were older, more frequently non-contact lens wearers and a had a higher prevalence of previous ocular surgeries and topical treatment. A lower clinical response to initial treatment was observed in resistant cases. Need for surgery and complications were higher among moxifloxacin-resistant cases.

Conclusions

This study reports for the first time in North America a progressive and significant increase in moxifloxacin resistance among PA isolates. Overuse of topical moxifloxacin may be underlying this finding. Given the worse clinical outcomes in resistant cases, we would caution against the use of moxifloxacin alone as empirical treatment of infectious keratitis.

目的：确定铜绿假单胞菌（PA）耐药性模式的趋势，并分析其临床结果。方法：从加拿大不列颠哥伦比亚省的眼部样本中收集了25年的PA分离物。记录来源及抗生素耐药性。分析并比较莫西沙星耐药和莫西沙星敏感的PA角膜炎患者的人口统计学资料、既往眼部病史和临床结果。结果：共检出321株假单胞菌，其中PA 297株（92.5%），占角膜标本的101.34%。氯霉素耐药率为88.7%，莫西沙星耐药率为23.7%，美罗培南耐药率为10.1%。莫西沙星耐药和非敏感性增加，妥布霉素耐药减少。其他氟喹诺酮类抗生素没有观察到同样的趋势。14株（4.7%）PA分离株多重耐药。临床分析53株PA角膜分离株：对莫西沙星敏感21株（40%），中间17株（32%），耐药15株（28%）。非易感PA患者年龄较大，经常佩戴非隐形眼镜，既往眼部手术和局部治疗的患病率较高。耐药病例对初始治疗的临床反应较低。莫西沙星耐药病例的手术需求和并发症较高。结论：本研究首次在北美报道了PA分离株中莫西沙星耐药性的进展性和显著性增加。过量使用局部莫西沙星可能是这一发现的基础。鉴于耐药病例的临床结果较差，我们建议不要单独使用莫西沙星作为感染性角膜炎的经验性治疗。

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引用次数: 0

Topical pharmacologic treatments for dry eye disease: A systematic review 干眼病的局部药物治疗：系统综述。

IF 5.6 1区医学 Q1 OPHTHALMOLOGY

Ocular Surface

Pub Date : 2025-07-30 DOI: 10.1016/j.jtos.2025.07.010

Louis Tong , Zuguo Liu , Afsun Şahin , Koray Gümüş , Elisabeth M. Messmer , José M. Benítez-del-Castillo , Marc Labetoulle , Clara C. Chan , Laura M. Periman

Background

Topical pharmacologic treatments for dry eye disease (DED) address different aspects of tear film deficiency by decreasing ocular surface inflammation, stimulating mucin secretion, increasing tear production, or reducing excessive evaporation. This systematic review evaluated randomized controlled trials (RCTs) and prospective observational studies of topical ophthalmic medications for DED.

Methods

PubMed and Embase were searched from 1980 to February 2024. For studies meeting inclusion criteria, efficacy outcomes (signs and symptoms of DED) and adverse event data were extracted.

Results

A total of 107 publications covering topical prescription medications (anti-inflammatory agents cyclosporine and lifitegrast; mucin secretagogues diquafosol and rebamipide; tear evaporation inhibitor perfluorohexyloctane; tear production stimulator nasal spray varenicline), other commercially available products, and novel agents in development were identified. In RCTs, significant improvements relative to a control group were demonstrated more often for sign endpoints (e.g., corneal staining, Schirmer score) than for symptom endpoints (e.g., eye dryness, ocular discomfort). The evaluated treatments were well tolerated; instillation site reactions were the most commonly reported adverse events. Year-long safety extension studies demonstrated maintenance of efficacy, with no new safety signals identified. Studies differed in design, methodology, control group, and outcomes assessment, making it difficult to compare across products, and head-to-head studies were rare. Several new products are in late-stage development, which will likely lead to additional treatment options.

Conclusions

Current topical pharmacologic eye products improved signs, and sometimes symptoms, of DED and were well tolerated. Treatment selection should use a shared decision-making approach that takes DED etiology and patient preferences into account.

背景：干眼病（DED）的局部药物治疗通过减少眼表炎症、刺激黏液分泌、增加泪液产生或减少过度蒸发来解决泪膜缺乏的不同方面。本系统综述评价了局部眼科药物治疗DED的随机对照试验（rct）和前瞻性观察性研究。方法：检索1980 ~ 2024年2月PubMed和Embase数据库。对于符合纳入标准的研究，提取疗效结局（DED的体征和症状）和不良事件数据。结果：共有107篇出版物涵盖了外用处方药(抗炎药环孢素和利替格司；粘蛋白分泌剂：双喹福醇和利巴米胺；撕裂蒸发抑制剂全氟己辛烷；确定了泪液产生刺激剂（varenicline鼻喷雾剂），其他市售产品和正在开发的新型药物。在随机对照试验中，与对照组相比，体征终点（如角膜染色、Schirmer评分）比症状终点（如眼睛干燥、眼部不适）更常表现出显著的改善。经评估的治疗方法耐受性良好；注射部位反应是最常见的不良事件。为期一年的安全性扩展研究表明，该药物维持了疗效，未发现新的安全信号。研究在设计、方法、对照组和结果评估方面存在差异，这使得很难对不同产品进行比较，而且针锋相对的研究很少。一些新产品正处于后期开发阶段，这可能会带来更多的治疗选择。结论：目前的局部药物眼科产品改善了DED的体征，有时是症状，并且耐受性良好。治疗选择应采用共同决策的方法，将DED病因和患者偏好考虑在内。

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引用次数: 0

New insight into the neuroimmune interplay in Pseudomonas aeruginosa keratitis 铜绿假单胞菌性角膜炎的神经免疫相互作用新认识

IF 5.6 1区医学 Q1 OPHTHALMOLOGY

Ocular Surface

Pub Date : 2025-07-24 DOI: 10.1016/j.jtos.2025.07.008

Naman Gupta, Giovanni LoGrasso, Linda D. Hazlett, Shunbin Xu

Purpose

This research aims to reveal the roles of the miR-183/96/182 cluster (miR-183C) in sensory neurons (SN) in the interplay of corneal sensory nerves (CSN) and myeloid cells (MC) during Pseudomonas aeruginosa (PA) keratitis.

Methods

The left corneas of SN-specific (SNS) conditional knockout (CKO) and their wild type (WT) littermates were infected with PA. CSN of these mice express RFP; MC EGFP. Confocal microscopy of corneal flatmount, myeloperoxidase (MPO) assay and plate count were performed.

Results

In WT mice, CSN began to degenerate at 3 h-post-infection (hpi), starting from epithelial/subepithelial layers in the central region. By 1 day-post-infection (dpi), epithelium/subepithelial CSN were nearly completely destroyed, while stromal nerves persisted. From 3 dpi, CSN were obliterated in both layers. In CKO vs WT mice, CSN density was decreased at 3 and 6 hpi; however, CNS degeneration followed a slower pace. At 3 dpi, residual large-diameter stromal CSN were better preserved.

MC were decreased in the central cornea at 3 and 6 hpi, but increased in the periphery, more prominent in CKO mice. At 12 hpi, densely packed MC formed a ring-shaped band circling a “dark” zone nearly devoid of MC, colocalizing with CSN most degenerated central area. At 1 dpi, the cornea was filled with MC; MC density was lower in CKO. CKO mice had decreased neutrophils at 1 dpi and reduced disease severity at 3 dpi.

Conclusions

Our results provide new insight into the neuroimmune interplay during PA keratitis. miR-183C in CSN modulates PA keratitis through regulation of neuroimmune interaction.

目的：本研究旨在揭示在铜绿假单胞菌（PA）性角膜炎中，感觉神经元中miR-183/96/182簇（miR-183C）在角膜感觉神经（CSN）和髓样细胞（MC）相互作用中的作用。方法：对sn特异性（SNS）条件敲除（CKO）的左眼角膜及其野生型（WT）幼崽进行PA感染。这些小鼠的CSN表达RFP；MC EGFP。角膜平片共聚焦显微镜，髓过氧化物酶（MPO）测定和平板计数。结果：在WT小鼠中，CSN在感染后3小时（hpi）开始变性，从中央区域的上皮/上皮下层开始。感染后1天（dpi），上皮/上皮下CSN几乎完全破坏，而间质神经持续存在。从3 dpi开始，两层的CSN均被抹去。在CKO和WT小鼠中，CSN密度在3和6 hpi时降低；然而，中枢神经系统退化的速度较慢。3 dpi时，残余大直径间质CSN保存较好。在3和6 hpi时，中央角膜MC减少，而周围角膜MC增加，在CKO小鼠中更为明显。在12 hpi时，密集的MC形成一个环状带，环绕着一个几乎没有MC的“黑暗”区，与CSN最退化的中心区共域。在1 dpi时，角膜充满MC；CKO组MC密度较低。CKO小鼠在1 dpi时中性粒细胞减少，在3 dpi时疾病严重程度降低。结论：我们的研究结果为PA角膜炎的神经免疫相互作用提供了新的见解。CSN中的miR-183C通过调节神经免疫相互作用调节PA角膜炎。

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引用次数: 0

Systemic immune checkpoint inhibitors: Successful treatment of conjunctival atypical melanocytic proliferation documented by anterior segment optical coherence tomography 系统性免疫检查点抑制剂：成功治疗结膜非典型黑素细胞增生的前段光学相干断层扫描记录

IF 5.6 1区医学 Q1 OPHTHALMOLOGY

Ocular Surface

Pub Date : 2025-07-19 DOI: 10.1016/j.jtos.2025.07.005

Gelila B. Yohannes , Nathan L. Scott , Wendy J. Li , Carol L. Karp

引用次数: 0

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