Pub Date : 2025-07-18DOI: 10.1016/j.jtos.2025.07.003
Juana Gallar , Stephen Pflugfelder , Anat Galor , Preeya K. Gupta , Pedram Hamrah
The lacrimal functional unit (LFU) tightly controls the secretion of all tear components, thus playing a critical role in maintaining ocular surface homeostasis. Forming an exquisitely sensitive neural network across the ocular surface, corneal sensory nerves detect environmental stimuli (e.g., temperature, chemicals, and mechanical pressure) through transient receptor potential (TRP) ion channels. Among these, TRP melastatin 8 (TRPM8) is a key regulator of basal tear production. Stimulated by the small temperature reductions and tear film osmolarity increases that arise due to evaporative cooling, TRPM8 activates the LFU, leading to increased basal tear production.
Here, we focus on reviewing the topical ocular pathways within the LFU that regulate tear production. We describe the neural signaling underlying this regulation, with a focus on TRP channels and the central role of TRPM8 in basal tear production as elucidated through preclinical as well as limited clinical evidence. Lastly, we explore how augmenting the fundamental action of TRPM8 signaling through agonist stimulation may serve as a valuable new treatment option for dry eye disease.
{"title":"Corneal sensory nerve regulation of tear production through stimulation of transient receptor potential melastatin 8 (TRPM8) channel: A potential new approach for treating dry eye disease","authors":"Juana Gallar , Stephen Pflugfelder , Anat Galor , Preeya K. Gupta , Pedram Hamrah","doi":"10.1016/j.jtos.2025.07.003","DOIUrl":"10.1016/j.jtos.2025.07.003","url":null,"abstract":"<div><div>The lacrimal functional unit (LFU) tightly controls the secretion of all tear components, thus playing a critical role in maintaining ocular surface homeostasis. Forming an exquisitely sensitive neural network across the ocular surface, corneal sensory nerves detect environmental stimuli (e.g., temperature, chemicals, and mechanical pressure) through transient receptor potential (TRP) ion channels. Among these, TRP melastatin 8 (TRPM8) is a key regulator of basal tear production. Stimulated by the small temperature reductions and tear film osmolarity increases that arise due to evaporative cooling, TRPM8 activates the LFU, leading to increased basal tear production.</div><div>Here, we focus on reviewing the topical ocular pathways within the LFU that regulate tear production. We describe the neural signaling underlying this regulation, with a focus on TRP channels and the central role of TRPM8 in basal tear production as elucidated through preclinical as well as limited clinical evidence. Lastly, we explore how augmenting the fundamental action of TRPM8 signaling through agonist stimulation may serve as a valuable new treatment option for dry eye disease.</div></div>","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":"38 ","pages":"Pages 142-154"},"PeriodicalIF":5.9,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144664776","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}
Pub Date : 2025-07-18DOI: 10.1016/j.jtos.2025.07.004
Shujia Guo , Jiayu Kang , Ke Yan , Jiani Li , Ruochen Wang , Danyi Qin , Yuqian Wang , Yuwen Liu , Wenying Guan , Han Wu , Jiaoyue Hu , Wei Li , Yongxiong Chen , Caihong Huang , Zuguo Liu
Purpose
To investigate Prostaglandin F2α (PGF2α) expression in dry eye (DE) patients and its correlation with clinical manifestations, exploring potential mechanisms in DE.
Methods
Cross-sectional case-control study including 21 DE patients and 16 controls. PGF2α levels were detected by ELISA (Enzyme-linked immunosorbent assay). Correlation analyses were conducted between PGF2α in human tears and DE symptoms (The Ocular Surface Disease Index, OSDI) or signs including tear film breakup time using fluorescein sodium strips (FBUT), Schirmer Ⅰ test (ST) and corneal fluorescein staining (CFS). Dry eye models were induced using scopolamine and desiccating stress, with transcriptomic sequencing to analyze differential gene expression. DE mice were treated with the PGF2α receptor inhibitor AL8810. Various assays (Oregon green dextran staining, phenol red thread test, PCR, immunofluorescence, MASSON staining, ELISA, Western Blot) evaluated DE phenotypes, lacrimal gland inflammation, and fibrosis.
Results
DE patients had significantly elevated PGF2α levels, negatively correlating with ST and positively with CFS. DE mice showed increased PGF2α and FP receptor expression in lacrimal glands, decreased tear production, worsening ocular surface damage, and elevated inflammation and fibrosis. The TGFβ1/Smads and RhoA/ROCKs pathways were activated, with changes becoming more pronounced with extended molding time. AL8810 reduced fibrosis, partially restored tear secretion, and alleviated corneal damage while inhibiting RhoA/ROCKs pathway activation without affecting TGFβ1 expression.
Conclusions
PGF2α exacerbated DE by promoting lacrimal gland fibrosis progression via the RhoA/ROCKs signaling pathway. Inhibiting PGF2α receptors effectively suppressed the progression of dry eye and lacrimal gland fibrosis, which may offer a promising therapeutic strategy for DE, particularly in refractory cases associated with lacrimal gland fibrosis.
{"title":"Prostaglandin F2α exacerbated dry eye by promoting lacrimal gland fibrosis progression through the activation of the RhoA/ROCKs signaling pathway","authors":"Shujia Guo , Jiayu Kang , Ke Yan , Jiani Li , Ruochen Wang , Danyi Qin , Yuqian Wang , Yuwen Liu , Wenying Guan , Han Wu , Jiaoyue Hu , Wei Li , Yongxiong Chen , Caihong Huang , Zuguo Liu","doi":"10.1016/j.jtos.2025.07.004","DOIUrl":"10.1016/j.jtos.2025.07.004","url":null,"abstract":"<div><h3>Purpose</h3><div>To investigate Prostaglandin F2α (PGF2α) expression in dry eye (DE) patients and its correlation with clinical manifestations, exploring potential mechanisms in DE.</div></div><div><h3>Methods</h3><div>Cross-sectional case-control study including 21 DE patients and 16 controls. PGF2α levels were detected by ELISA (Enzyme-linked immunosorbent assay). Correlation analyses were conducted between PGF2α in human tears and DE symptoms (The Ocular Surface Disease Index, OSDI) or signs including tear film breakup time using fluorescein sodium strips (FBUT), Schirmer Ⅰ test (ST) and corneal fluorescein staining (CFS). Dry eye models were induced using scopolamine and desiccating stress, with transcriptomic sequencing to analyze differential gene expression. DE mice were treated with the PGF2α receptor inhibitor AL8810. Various assays (Oregon green dextran staining, phenol red thread test, PCR, immunofluorescence, MASSON staining, ELISA, Western Blot) evaluated DE phenotypes, lacrimal gland inflammation, and fibrosis.</div></div><div><h3>Results</h3><div>DE patients had significantly elevated PGF2α levels, negatively correlating with ST and positively with CFS. DE mice showed increased PGF2α and FP receptor expression in lacrimal glands, decreased tear production, worsening ocular surface damage, and elevated inflammation and fibrosis. The TGFβ1/Smads and RhoA/ROCKs pathways were activated, with changes becoming more pronounced with extended molding time. AL8810 reduced fibrosis, partially restored tear secretion, and alleviated corneal damage while inhibiting RhoA/ROCKs pathway activation without affecting TGFβ1 expression.</div></div><div><h3>Conclusions</h3><div>PGF2α exacerbated DE by promoting lacrimal gland fibrosis progression via the RhoA/ROCKs signaling pathway. Inhibiting PGF2α receptors effectively suppressed the progression of dry eye and lacrimal gland fibrosis, which may offer a promising therapeutic strategy for DE, particularly in refractory cases associated with lacrimal gland fibrosis.</div></div>","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":"38 ","pages":"Pages 155-169"},"PeriodicalIF":5.9,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144664961","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}
Pub Date : 2025-07-10DOI: 10.1016/j.jtos.2025.07.001
Seung Hyeun Lee , Soo Jin Lee , Ahra Koh , Yunjin Lee , Seonghan Kim , Suil Jeon , Noseong Park , Chang Ho Yoon , Ki Hean Kim , Kyoung Woo Kim
Purpose
Corneal nerve fibers and resident macrophages form a specialized microenvironment essential for tissue integrity and recovery after injury. This study aims to elucidate the early immune dynamics following corneal nerve injury, focusing on myeloid cell infiltration and resident macrophage subset shifts.
Methods
Using a murine circular nerve-cut model, we tracked immune responses for 21 days, with a focus on the first 12 h post-injury. Confocal imaging was used to assess corneal nerve density, while flow cytometry quantified infiltrating and resident immune cell populations. Transcriptomic profiling was performed at 3 and 6 h post-injury to analyze inflammatory gene expression, and in vitro experiments examined the effects of short-term nerve growth factor (NGF) exposure on macrophage polarization.
Results
Confocal imaging showed a rapid decrease in corneal nerve density, followed by progressive regeneration. Flow cytometry revealed a surge in Ly6C+ myeloid cells at 3–6 h post-injury, predominantly in the central cornea, with an early tendency toward M2-like polarization. Resident macrophages exhibited distinct responses: M2-like and undifferentiated subsets declined, while M1-like cells were proportionally maintained, indicating divergent but complementary roles during the initial inflammatory phase. Transcriptomic profiling showed significant upregulation of inflammatory genes along with a transient increase in Ngf and compensatory anti-inflammatory signaling. In vitro, short-term NGF exposure enhanced both M1-and M2-like polarization, mirroring in vivo activation patterns.
Conclusion
Early myeloid cell infiltration and macrophage subset dynamics contribute to the initial neuroinflammatory response and may influence subsequent repair processes, highlighting the potential for immune modulation in corneal nerve regeneration.
{"title":"Early myeloid cell infiltration and subset-specific macrophage responses in murine corneal nerve injury","authors":"Seung Hyeun Lee , Soo Jin Lee , Ahra Koh , Yunjin Lee , Seonghan Kim , Suil Jeon , Noseong Park , Chang Ho Yoon , Ki Hean Kim , Kyoung Woo Kim","doi":"10.1016/j.jtos.2025.07.001","DOIUrl":"10.1016/j.jtos.2025.07.001","url":null,"abstract":"<div><h3>Purpose</h3><div>Corneal nerve fibers and resident macrophages form a specialized microenvironment essential for tissue integrity and recovery after injury. This study aims to elucidate the early immune dynamics following corneal nerve injury, focusing on myeloid cell infiltration and resident macrophage subset shifts.</div></div><div><h3>Methods</h3><div>Using a murine circular nerve-cut model, we tracked immune responses for 21 days, with a focus on the first 12 h post-injury. Confocal imaging was used to assess corneal nerve density, while flow cytometry quantified infiltrating and resident immune cell populations. Transcriptomic profiling was performed at 3 and 6 h post-injury to analyze inflammatory gene expression, and <em>in vitro</em> experiments examined the effects of short-term nerve growth factor (NGF) exposure on macrophage polarization.</div></div><div><h3>Results</h3><div>Confocal imaging showed a rapid decrease in corneal nerve density, followed by progressive regeneration. Flow cytometry revealed a surge in Ly6C<sup>+</sup> myeloid cells at 3–6 h post-injury, predominantly in the central cornea, with an early tendency toward M2-like polarization. Resident macrophages exhibited distinct responses: M2-like and undifferentiated subsets declined, while M1-like cells were proportionally maintained, indicating divergent but complementary roles during the initial inflammatory phase. Transcriptomic profiling showed significant upregulation of inflammatory genes along with a transient increase in <em>Ngf</em> and compensatory anti-inflammatory signaling. <em>In vitro</em>, short-term NGF exposure enhanced both M1-and M2-like polarization, mirroring <em>in vivo</em> activation patterns.</div></div><div><h3>Conclusion</h3><div>Early myeloid cell infiltration and macrophage subset dynamics contribute to the initial neuroinflammatory response and may influence subsequent repair processes, highlighting the potential for immune modulation in corneal nerve regeneration.</div></div>","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":"38 ","pages":"Pages 117-131"},"PeriodicalIF":5.9,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144613297","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}
Pub Date : 2025-06-23DOI: 10.1016/j.jtos.2025.06.008
Raven Diacou , Rohan Bir Singh , Eric G. Romanowski , Jonathan B. Mandell , Alex Mammen , Robert M.Q. Shanks , Vishal Jhanji
Purpose
Fluoroquinolones, specifically moxifloxacin are commonly used to treat bacterial keratitis. However, recent clinical evidence assessing the clinical outcomes in bacterial keratitis cases resistant to moxifloxacin remains sparse. This study evaluates the clinical characteristics and outcomes in cases of Staphylococcus aureus keratitis with in vitro resistance to moxifloxacin.
Design
Retrospective clinical cohort study.
Methods
Keratitis patients with cultures positive for Staphylococcus aureus at the University of Pittsburgh Medical Center, were identified between July 2012 and June 2022.
Results
A total of 104 patients with culture-confirmed Staphylococcus aureus keratitis were included in the study. Patients infected by moxifloxacin-resistant bacteria (n = 32) were significantly older (74.32 ± 17.41 years) than moxifloxacin-susceptible infections (55.56 ± 20.86 years, p < 0.0001). Moxifloxacin resistance was identified in 29.8 % of cases, including methicillin-susceptible (4.8 %) and methicillin-resistant Staphylococcus aureus (25.96 %) isolates. The most common risk factors for moxifloxacin resistance were ocular surface disease (35.5 %) and history of prior infection (32.2 %). Moxifloxacin-resistant Staphylococcus aureus was associated with larger epithelial defects (18.18 ± 4.93 mm2 vs. 5.10 ± 0.76 mm2, p < 0.0001), longer healing times (42.42 ± 6.75 days vs. 32.2 ± 3.56 days, p < 0.0001), and higher rates of corneal perforation (19.3 % vs. 4.2 %; p = 0.0317). Visual acuity outcomes were significantly worse in the resistant group, with minimal improvement from baseline (1.87 ± 0.14 LogMAR) to final follow-up (1.8 ± 0.18 LogMAR), compared to the moxifloxacin-susceptible group (from 1.46 ± 0.11 LogMAR to 1.15 ± 0.11 LogMAR, p < 0.0001). Enucleation was required in 9.6 % of resistant cases.
Conclusions
The current study determined significant differences in clinical characteristics and outcomes among corneal ulcers caused by moxifloxacin-resistant Staphylococcus aureus.
目的氟喹诺酮类药物，特别是莫西沙星常用于治疗细菌性角膜炎。然而，最近评估细菌性角膜炎对莫西沙星耐药的临床结果的临床证据仍然很少。本研究对莫西沙星体外耐药金黄色葡萄球菌角膜炎的临床特点和预后进行了评价。设计回顾性临床队列研究。方法选取2012年7月至2022年6月在匹兹堡大学医学中心发现的金黄色葡萄球菌培养阳性的角膜炎患者。结果共纳入104例经培养证实的金黄色葡萄球菌角膜炎患者。莫西沙星耐药菌感染患者（n = 32）年龄（74.32±17.41岁）明显大于莫西沙星敏感菌感染患者(55.56±20.86岁，p <；0.0001)。29.8%的病例耐莫西沙星，其中甲氧西林敏感（4.8%）和耐甲氧西林金黄色葡萄球菌（25.96%）。莫西沙星耐药最常见的危险因素是眼表疾病（35.5%）和既往感染史（32.2%）。耐莫西沙星金黄色葡萄球菌与较大的上皮缺损相关(18.18±4.93 mm2 vs. 5.10±0.76 mm2, p <；0.0001)，较长的愈合时间(42.42±6.75天vs. 32.2±3.56天，p <；0.0001)，角膜穿孔率较高(19.3% vs. 4.2%；p = 0.0317)。与莫西沙星敏感组（从1.46±0.11 LogMAR到1.15±0.11 LogMAR）相比，耐药组的视力结果明显更差，从基线（1.87±0.14 LogMAR）到最终随访（1.8±0.18 LogMAR）的改善极小(p <；0.0001)。9.6%的耐药病例需要去核。结论本研究确定了耐莫西沙星金黄色葡萄球菌引起的角膜溃疡的临床特征和结局存在显著差异。
{"title":"Moxifloxacin-resistant and moxifloxacin-susceptible Staphylococcus aureus Keratitis: Outcomes from a 10-year retrospective study","authors":"Raven Diacou , Rohan Bir Singh , Eric G. Romanowski , Jonathan B. Mandell , Alex Mammen , Robert M.Q. Shanks , Vishal Jhanji","doi":"10.1016/j.jtos.2025.06.008","DOIUrl":"10.1016/j.jtos.2025.06.008","url":null,"abstract":"<div><h3>Purpose</h3><div>Fluoroquinolones, specifically moxifloxacin are commonly used to treat bacterial keratitis. However, recent clinical evidence assessing the clinical outcomes in bacterial keratitis cases resistant to moxifloxacin remains sparse. This study evaluates the clinical characteristics and outcomes in cases of <em>Staphylococcus aureus</em> keratitis with <em>in vitro</em> resistance to moxifloxacin.</div></div><div><h3>Design</h3><div>Retrospective clinical cohort study.</div></div><div><h3>Methods</h3><div>Keratitis patients with cultures positive for <em>Staphylococcus aureus</em> at the University of Pittsburgh Medical Center, were identified between July 2012 and June 2022.</div></div><div><h3>Results</h3><div>A total of 104 patients with culture-confirmed <em>Staphylococcus aureus</em> keratitis were included in the study. Patients infected by moxifloxacin-resistant bacteria (n = 32) were significantly older (74.32 ± 17.41 years) than moxifloxacin-susceptible infections (55.56 ± 20.86 years, p < 0.0001). Moxifloxacin resistance was identified in 29.8 % of cases, including methicillin-susceptible (4.8 %) and methicillin-resistant <em>Staphylococcus aureus</em> (25.96 %) isolates. The most common risk factors for moxifloxacin resistance were ocular surface disease (35.5 %) and history of prior infection (32.2 %). Moxifloxacin-resistant <em>Staphylococcus aureus</em> was associated with larger epithelial defects (18.18 ± 4.93 mm<sup>2</sup> vs. 5.10 ± 0.76 mm<sup>2</sup>, p < 0.0001), longer healing times (42.42 ± 6.75 days vs. 32.2 ± 3.56 days, p < 0.0001), and higher rates of corneal perforation (19.3 % vs. 4.2 %; p = 0.0317). Visual acuity outcomes were significantly worse in the resistant group, with minimal improvement from baseline (1.87 ± 0.14 LogMAR) to final follow-up (1.8 ± 0.18 LogMAR), compared to the moxifloxacin-susceptible group (from 1.46 ± 0.11 LogMAR to 1.15 ± 0.11 LogMAR, p < 0.0001). Enucleation was required in 9.6 % of resistant cases.</div></div><div><h3>Conclusions</h3><div>The current study determined significant differences in clinical characteristics and outcomes among corneal ulcers caused by moxifloxacin-resistant <em>Staphylococcus aureus</em>.</div></div>","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":"38 ","pages":"Pages 97-103"},"PeriodicalIF":5.9,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144471883","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}
Pub Date : 2025-06-23DOI: 10.1016/j.jtos.2025.06.009
Jinghua Bu , Yuli Guo , Yang Wu , Rongrong Zhang , Jingbin Zhuang , Jiankai Zhao , Le Sun , Andrew J. Quantock , Zuguo Liu , Wei Li
{"title":"Corrigendum to “Models for Meibomian gland dysfunction: In vivo and in vitro”, Review article [Ocul. Surf. 32 (2024) 154–165]","authors":"Jinghua Bu , Yuli Guo , Yang Wu , Rongrong Zhang , Jingbin Zhuang , Jiankai Zhao , Le Sun , Andrew J. Quantock , Zuguo Liu , Wei Li","doi":"10.1016/j.jtos.2025.06.009","DOIUrl":"10.1016/j.jtos.2025.06.009","url":null,"abstract":"","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":"38 ","pages":"Page 116"},"PeriodicalIF":5.9,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144500002","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}
Pub Date : 2025-06-20DOI: 10.1016/j.jtos.2025.06.006
Liyun Wang , Hongbo Yin , Yujia Yang , Li Qiu
Purpose
We employed 24 MHz ultrasonography to evaluate the morphological features of meibomian glands (MGs) and compared the ultrasonic differences in morphology between healthy volunteers and meibomian gland dysfunction (MGD) patients.
Methods
24 MHz ultrasound examinations on both the upper and lower eyelids of healthy volunteers and patients with MGD, using transverse and longitudinal sections. The reproducibility of ultrasonographic findings for the MG was evaluated, and a comparison of morphological characteristics at different examination sites between the two groups was made.
Results
Among 89 participants, 24 were healthy volunteers and 65 had MGD. The cross-sectional ultrasound findings showed well-organized punctate hyperechoic ducts within the tarsal plate, surrounded by hypoechoic acinar formations, which were further classified based on the extent of MG involvement into three categories: normal, ≤50 % involvement, and >50 % involvement. Additionally, a typical longitudinal ultrasound appearance of a MG consisted of a thin band-like hypoechoic structure (acinar) with uniform thickness accompanied by an arc-shaped linear hyperechoic duct in its middle region. Furthermore, seven abnormal longitudinal ultrasound manifestations were categorized as distortion, ectasia, central duct truncation, cyst formation, structureless appearance, complete disappearance or other findings. The intra- and inter-observer agreement for those categories was found to be high (ICC>0.6). MGD patients exhibited a higher likelihood of overall MG involvement or abnormal ultrasound findings, particularly in relation to the middle part of the upper eyelid.
Conclusion
The present study has developed an initial classification method to identify abnormalities in MG morphology using 24 MHz ultrasound in MGD patients.
{"title":"Ultrasonography assessments of meibomian gland as a noninvasive method of detecting changes in morphology","authors":"Liyun Wang , Hongbo Yin , Yujia Yang , Li Qiu","doi":"10.1016/j.jtos.2025.06.006","DOIUrl":"10.1016/j.jtos.2025.06.006","url":null,"abstract":"<div><h3>Purpose</h3><div>We employed 24 MHz ultrasonography to evaluate the morphological features of meibomian glands (MGs) and compared the ultrasonic differences in morphology between healthy volunteers and meibomian gland dysfunction (MGD) patients.</div></div><div><h3>Methods</h3><div>24 MHz ultrasound examinations on both the upper and lower eyelids of healthy volunteers and patients with MGD, using transverse and longitudinal sections. The reproducibility of ultrasonographic findings for the MG was evaluated, and a comparison of morphological characteristics at different examination sites between the two groups was made.</div></div><div><h3>Results</h3><div>Among 89 participants, 24 were healthy volunteers and 65 had MGD. The cross-sectional ultrasound findings showed well-organized punctate hyperechoic ducts within the tarsal plate, surrounded by hypoechoic acinar formations, which were further classified based on the extent of MG involvement into three categories: normal, ≤50 % involvement, and >50 % involvement. Additionally, a typical longitudinal ultrasound appearance of a MG consisted of a thin band-like hypoechoic structure (acinar) with uniform thickness accompanied by an arc-shaped linear hyperechoic duct in its middle region. Furthermore, seven abnormal longitudinal ultrasound manifestations were categorized as distortion, ectasia, central duct truncation, cyst formation, structureless appearance, complete disappearance or other findings. The intra- and inter-observer agreement for those categories was found to be high (ICC>0.6). MGD patients exhibited a higher likelihood of overall MG involvement or abnormal ultrasound findings, particularly in relation to the middle part of the upper eyelid.</div></div><div><h3>Conclusion</h3><div>The present study has developed an initial classification method to identify abnormalities in MG morphology using 24 MHz ultrasound in MGD patients.</div></div>","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":"38 ","pages":"Pages 72-79"},"PeriodicalIF":5.9,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144337791","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}
Pub Date : 2025-06-20DOI: 10.1016/j.jtos.2025.06.005
Soumen Sadhu , Isabelle Jalbert , Luz Palacios-Derflingher , Ali Alghamdi , Blanka Golebiowski , Fiona Stapleton
Purpose
To examine ocular surface epithelial immune cell (EIC) density and corneal nerve parameters between patients with dry eye disease (DED) compared to healthy controls with further comparisons between auto-immune - Sjӧgren Syndrome DED (SS-DED) and non-autoimmune – non-Sjӧgren Syndrome DED (NSS-DED) subtypes.
Methods
A systematic review and meta-analysis following PRISMA guidelines (Prospero-CRD42023446763) were conducted including studies reporting corneal and conjunctival EIC density and/or corneal nerve parameters in DED and healthy controls using in vivo confocal microscopy. Electronic databases – PubMed, Embase, Scopus, Web of Science were searched from inception to March 2025.
Results
The meta-analysis included 24 studies (n = 1060 DED, n = 521 controls) reporting EIC density, 30 studies reporting nerve length (CNL; n = 1450 DED, n = 643 controls) and 20 studies reporting nerve density (CND; n = 919 DED, n = 462 controls) in the central cornea. Studies of other ocular surface locations were insufficient for meta-analysis. Higher central corneal EIC density was evident in DED compared to controls (MD: 57.9 cells/mm2; 95 % CI: 43.3, 72.5; p < 0.001), and in, SS-DED compared to NSS-DED (51.0 cells/mm2; 95 % CI: 12.0, 90.0; p = 0.01). DED had lower CNL (−4.0 mm/mm2; 95 % CI: 5.2, −2.7; p < 0.001) and CND (−7.2 nerves/mm2; 95 % CI: 10.3, −4.1; p < 0.001) compared to controls. No significant differences in nerve parameters were found between SS-DED and NSS-DED subtypes (CNL: 95 % CI: 3.0, 1.4, CND: 6.8, 4.8; p ≥ 0.46).
Conclusion
DED involves substantial EIC infiltration and reduced corneal nerve parameters. SS-DED is distinguished by higher EIC density than NSS-DED, while no differences were observed in corneal nerve parameters.
{"title":"Ocular surface epithelial immune cells and corneal nerves in dry eye disease - A systematic review and meta-analysis of in vivo confocal microscopy data","authors":"Soumen Sadhu , Isabelle Jalbert , Luz Palacios-Derflingher , Ali Alghamdi , Blanka Golebiowski , Fiona Stapleton","doi":"10.1016/j.jtos.2025.06.005","DOIUrl":"10.1016/j.jtos.2025.06.005","url":null,"abstract":"<div><h3>Purpose</h3><div>To examine ocular surface epithelial immune cell (EIC) density and corneal nerve parameters between patients with dry eye disease (DED) compared to healthy controls with further comparisons between auto-immune - Sjӧgren Syndrome DED (SS-DED) and non-autoimmune – non-Sjӧgren Syndrome DED (NSS-DED) subtypes.</div></div><div><h3>Methods</h3><div>A systematic review and meta-analysis following PRISMA guidelines (Prospero-CRD42023446763) were conducted including studies reporting corneal and conjunctival EIC density and/or corneal nerve parameters in DED and healthy controls using <em>in vivo</em> confocal microscopy. Electronic databases – PubMed, Embase, Scopus, Web of Science were searched from inception to March 2025.</div></div><div><h3>Results</h3><div>The meta-analysis included 24 studies (n = 1060 DED, n = 521 controls) reporting EIC density, 30 studies reporting nerve length (CNL; n = 1450 DED, n = 643 controls) and 20 studies reporting nerve density (CND; n = 919 DED, n = 462 controls) in the central cornea. Studies of other ocular surface locations were insufficient for meta-analysis. Higher central corneal EIC density was evident in DED compared to controls (MD: 57.9 cells/mm<sup>2</sup>; 95 % CI: 43.3, 72.5; p < 0.001), and in, SS-DED compared to NSS-DED (51.0 cells/mm<sup>2</sup>; 95 % CI: 12.0, 90.0; p = 0.01). DED had lower CNL (−4.0 mm/mm<sup>2</sup>; 95 % CI: 5.2, −2.7; p < 0.001) and CND (−7.2 nerves/mm<sup>2</sup>; 95 % CI: 10.3, −4.1; p < 0.001) compared to controls. No significant differences in nerve parameters were found between SS-DED and NSS-DED subtypes (CNL: 95 % CI: 3.0, 1.4, CND: 6.8, 4.8; p ≥ 0.46).</div></div><div><h3>Conclusion</h3><div>DED involves substantial EIC infiltration and reduced corneal nerve parameters. SS-DED is distinguished by higher EIC density than NSS-DED, while no differences were observed in corneal nerve parameters.</div></div>","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":"38 ","pages":"Pages 80-96"},"PeriodicalIF":5.9,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144337790","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}
Pub Date : 2025-06-19DOI: 10.1016/j.jtos.2025.06.007
Ema V. Karakoleva , Nicholas Pondelis , Cameron Talbert , Mariela C. Aguilar , Alex Gonzalez , Cornelis Rowaan , Heather Durkee , Paula A. Sepulveda-Beltran , David Valdes-Arias , Chloe Shields , Shreya Bhatt , David Zurakowski , Deborah S. Jacobs , Joseph B. Ciolino , Elizabeth R. Felix , Jean-Marie Parel , Eric A. Moulton , Anat Galor
Purpose
To quantify visual photosensitivity discomfort thresholds (VPDT) in individuals with chronic ocular pain (COP) compared to controls without COP and explore relationships between VPDT, demographics, clinical factors, and ocular metrics.
Methods
Prospective case-control study of 75 participants: 36 with COP (age 46.5 ± 15.6 years; 56 % female) and 39 controls (39.2 ± 15.6 years; 56 % female). COP was defined by self-reported ocular pain intensity ≥15 on a numerical rating scale (range, 0–100) for ≥3 months. COP cases were subclassified into inflammatory (Sjögren's disease) and neuropathic ocular pain subgroups. VPDT was measured using the Ocular Photosensitivity Analyzer (OPA), and ocular symptoms were assessed using the Visual Light Sensitivity Questionnaire (VLSQ-8; 8–40) and Ocular Surface Disease Index (OSDI; 0–100), with OSDI Question 1 addressing light sensitivity (OSDI-Q1; 0–4).
Results
COP patients exhibited lower VPDT than controls (log lux, 1.60 ± 1.17 vs. 2.42 ± 1.05; P = 0.006), indicating greater photosensitivity discomfort. No differences in VPDT were seen across COP subtypes. COP patients also reported greater symptom severity than controls, with higher VLSQ-8 (21.92 ± 1.41 vs. 9.03 ± 0.53), OSDI (50.84 ± 3.88 vs. 2.82 ± 0.85), and OSDI-Q1 (2.00 ± 0.24 vs. 0.14 ± 0.06) scores (all P < 0.001). VPDT negatively correlated with VLSQ-8 (ρ = −0.75) and OSDI-Q1 (ρ = −0.62), demonstrating alignment between subjective light sensitivity symptoms and OPA-measured photosensitivity discomfort. Multivariable regression identified fibromyalgia as the strongest predictor of VPDT (19.6 % variance explained), with chronic fatigue improving the model (26.5 %).
Conclusion
COP subjects display greater photosensitivity-related discomfort than controls, highlighting the OPA's potential as a psychophysical tool for quantifying photoallodynia. Further research is needed to assess its diagnostic utility across COP subtypes.
{"title":"Heightened visual light sensitivity discomfort measured by the ocular photosensitivity analyzer is associated with chronic ocular pain","authors":"Ema V. Karakoleva , Nicholas Pondelis , Cameron Talbert , Mariela C. Aguilar , Alex Gonzalez , Cornelis Rowaan , Heather Durkee , Paula A. Sepulveda-Beltran , David Valdes-Arias , Chloe Shields , Shreya Bhatt , David Zurakowski , Deborah S. Jacobs , Joseph B. Ciolino , Elizabeth R. Felix , Jean-Marie Parel , Eric A. Moulton , Anat Galor","doi":"10.1016/j.jtos.2025.06.007","DOIUrl":"10.1016/j.jtos.2025.06.007","url":null,"abstract":"<div><h3>Purpose</h3><div>To quantify visual photosensitivity discomfort thresholds (VPDT) in individuals with chronic ocular pain (COP) compared to controls without COP and explore relationships between VPDT, demographics, clinical factors, and ocular metrics.</div></div><div><h3>Methods</h3><div>Prospective case-control study of 75 participants: 36 with COP (age 46.5 ± 15.6 years; 56 % female) and 39 controls (39.2 ± 15.6 years; 56 % female). COP was defined by self-reported ocular pain intensity ≥15 on a numerical rating scale (range, 0–100) for ≥3 months. COP cases were subclassified into inflammatory (Sjögren's disease) and neuropathic ocular pain subgroups. VPDT was measured using the Ocular Photosensitivity Analyzer (OPA), and ocular symptoms were assessed using the Visual Light Sensitivity Questionnaire (VLSQ-8; 8–40) and Ocular Surface Disease Index (OSDI; 0–100), with OSDI Question 1 addressing light sensitivity (OSDI-Q1; 0–4).</div></div><div><h3>Results</h3><div>COP patients exhibited lower VPDT than controls (log lux, 1.60 ± 1.17 vs. 2.42 ± 1.05; P = 0.006), indicating greater photosensitivity discomfort. No differences in VPDT were seen across COP subtypes. COP patients also reported greater symptom severity than controls, with higher VLSQ-8 (21.92 ± 1.41 vs. 9.03 ± 0.53), OSDI (50.84 ± 3.88 vs. 2.82 ± 0.85), and OSDI-Q1 (2.00 ± 0.24 vs. 0.14 ± 0.06) scores (all P < 0.001). VPDT negatively correlated with VLSQ-8 (ρ = −0.75) and OSDI-Q1 (ρ = −0.62), demonstrating alignment between subjective light sensitivity symptoms and OPA-measured photosensitivity discomfort. Multivariable regression identified fibromyalgia as the strongest predictor of VPDT (19.6 % variance explained), with chronic fatigue improving the model (26.5 %).</div></div><div><h3>Conclusion</h3><div>COP subjects display greater photosensitivity-related discomfort than controls, highlighting the OPA's potential as a psychophysical tool for quantifying photoallodynia. Further research is needed to assess its diagnostic utility across COP subtypes.</div></div>","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":"38 ","pages":"Pages 64-71"},"PeriodicalIF":5.9,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144337728","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}
Pub Date : 2025-06-18DOI: 10.1016/j.jtos.2025.06.004
Asha Parvathaneni , Liliya Benchetrit , Derek Metcalfe , James T. Kwan , Yandong Bian , Tavé Van Zyl , Hajirah N. Saeed , James Chodosh
Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) is an acute, severe immunobullous disorder of skin and mucous membranes that is most commonly induced by exposure to drugs. Causation of SJS/TEN is most often determined by the “algorithm of drug causality for epidermal necrolysis” (ALDEN) tool. However, concerns remain regarding the precision of ALDEN and causality assessment tools, potentially impacting ongoing studies attempting to link specific genotypes with specific drug classes as causes. To determine whether a standard of care exists in attribution of causation in SJS/TEN, we performed a narrative review of current concepts on causation in SJS/TEN, and available clinical and laboratory assessment tools for attributing causation. We found that current SJS/TEN causality attribution tools, including ALDEN, are somewhat limited by underlying assumptions. The utility of ex vivo tests proposed for determining causation in SJS/TEN, specifically the lymphocyte transformation test and cytokine stimulation assays, remain under investigation and are either not tractable for acute SJS/TEN or are not yet validated. In summary, a critical unmet need exists in the care of SJS/TEN patients, namely the difficulty in determining a precise cause in any specific individual. This shortfall limits the clinician's ability to discontinue only the causal agent in the acute phase, confounds studies of pathogenesis, and leaves affected patients in the chronic phase without knowing which drug or drug class is safe to use in the future. Further studies are needed to close this critical gap in the care of this devastating disease.
{"title":"Attribution of causality in Stevens-Johnson syndrome/toxic epidermal necrolysis","authors":"Asha Parvathaneni , Liliya Benchetrit , Derek Metcalfe , James T. Kwan , Yandong Bian , Tavé Van Zyl , Hajirah N. Saeed , James Chodosh","doi":"10.1016/j.jtos.2025.06.004","DOIUrl":"10.1016/j.jtos.2025.06.004","url":null,"abstract":"<div><div>Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) is an acute, severe immunobullous disorder of skin and mucous membranes that is most commonly induced by exposure to drugs. Causation of SJS/TEN is most often determined by the “algorithm of drug causality for epidermal necrolysis” (ALDEN) tool. However, concerns remain regarding the precision of ALDEN and causality assessment tools, potentially impacting ongoing studies attempting to link specific genotypes with specific drug classes as causes. To determine whether a standard of care exists in attribution of causation in SJS/TEN, we performed a narrative review of current concepts on causation in SJS/TEN, and available clinical and laboratory assessment tools for attributing causation. We found that current SJS/TEN causality attribution tools, including ALDEN, are somewhat limited by underlying assumptions. The utility of <em>ex vivo</em> tests proposed for determining causation in SJS/TEN, specifically the lymphocyte transformation test and cytokine stimulation assays, remain under investigation and are either not tractable for acute SJS/TEN or are not yet validated. In summary, a critical unmet need exists in the care of SJS/TEN patients, namely the difficulty in determining a precise cause in any specific individual. This shortfall limits the clinician's ability to discontinue only the causal agent in the acute phase, confounds studies of pathogenesis, and leaves affected patients in the chronic phase without knowing which drug or drug class is safe to use in the future. Further studies are needed to close this critical gap in the care of this devastating disease.</div></div>","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":"38 ","pages":"Pages 104-112"},"PeriodicalIF":5.9,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144337403","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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