Pub Date : 2025-10-01Epub Date: 2025-08-18DOI: 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.
{"title":"Clinical recommendations for the management of Pythium insidiosum keratitis","authors":"Bhupesh Bagga , Lakshminarayanan Gowtham , Ali R. Djalilian , Savitri Sharma","doi":"10.1016/j.jtos.2025.08.003","DOIUrl":"10.1016/j.jtos.2025.08.003","url":null,"abstract":"<div><div><em>Pythium insidiosum</em> 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 <em>in vitro</em> and <em>in vivo</em> 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.</div></div>","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":"38 ","pages":"Pages 242-250"},"PeriodicalIF":5.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144893614","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 : 2025-10-01Epub Date: 2025-05-12DOI: 10.1016/j.jtos.2025.05.002
Celine Nguyen , Ebuka Eziama , Arturo R. Dominguez , Jennifer H. Cao
Objective
To evaluate the efficacy of Janus kinase inhibitor (JAKi) therapy in managing cicatrizing conjunctivitis associated with ocular cicatricial pemphigoid (OCP) and mucous membrane pemphigoid with ocular involvement (ocMMP).
Methods
Retrospective chart review of patients with cicatrizing conjunctivitis secondary to OCP or ocMMP who underwent treatment with JAKi at a tertiary academic medical center from August 2015 to November 2024 for minimum follow-up of six months. Collected data included demographics, Foster stage of cicatrization, and treatment course.
Results
Thirty-two patients met inclusion criteria: 23 (71.9 %) with OCP and 9 (28.1 %) with ocMMP. 96.9 % of patients demonstrated clinical improvement within twelve months of treatment initiation. Best response achieved were as follows: 1 (3.1 %) no response, 17 (53.1 %) partial response, 14 (43.8 %) complete remission, and 12 (37.5 %) steroid-free complete remission. The mean time to partial response, complete remission, steroid-free complete remission was 3.1 ± 1.8 (range, 0.9–8.3), 7.8 ± 3.3 months (range, 2.3–14.7 months), and 10.3 ± 7.4 months, (range, 2.3–31.4 months), respectively. Relapse in disease activity occurred in 8/32 (25.0 %) of patients. Side effects occurred in 8/32 (25.0 %) of patients. Four patients (12.5 %) discontinued therapy due to severe adverse events, including transient ischemic attack, pulmonary embolism, pyelonephritis, and cholecystitis. There was a significant association between lower Foster cicatrization stages and achieving remission (U = 630.0, p = 0.0036), with a rank-biserial correlation of 0.72.
Conclusions
JAK inhibitor therapy demonstrates efficacy in the management of recalcitrant cicatrizing conjunctivitis associated with pemphigoid. These findings highlight JAK inhibitors as a promising therapeutic option for refractory cases.
目的：评价Janus激酶抑制剂（JAKinib）治疗瘢痕性结膜炎伴眼瘢痕性类天疱疮（OCP）和黏膜类天疱疮伴眼累及（ocMMP）的疗效。方法：回顾性分析2015年8月至2024年11月在某三级学术医疗中心接受JAKinibs治疗的OCP或ocMMP继发瘢痕性结膜炎患者，随访时间至少为6个月。收集的数据包括人口统计学、愈合培养阶段和疗程。结果：32例患者符合纳入标准：OCP 23例（71.9%），ocMMP 9例（28.1%）。96.9%的患者在开始治疗的12个月内表现出临床改善。获得的最佳缓解如下：1例（3.1%）无缓解，17例（53.1%）部分缓解，14例（43.8%）完全临床缓解，12例（37.5%）无类固醇缓解。达到部分缓解、完全临床缓解和无类固醇缓解的平均时间分别为3.1±1.8个月（范围0.9-8.3）、7.8±3.3个月（范围2.3-14.7个月）和10.3±7.4个月（范围2.3-31.4个月）。8/32（25.0%）患者出现疾病活动复发。32例患者中有8例（25.0%）出现不良反应。4例患者（12.5%）因严重不良事件停止治疗，包括短暂性脑缺血发作、肺栓塞、肾盂肾炎和胆囊炎。较低的福斯特愈合阶段与获得缓解之间存在显著相关（U = 630.0, p = 0.0036），秩双列相关系数为0.72。结论：JAK抑制剂治疗与类天疱疮相关的顽固性结膜炎有效。这些发现突出了JAK抑制剂作为难治性病例的一种有希望的治疗选择。
{"title":"Janus kinase inhibitors in the treatment of refractory cicatrizing conjunctivitis in pemphigoid","authors":"Celine Nguyen , Ebuka Eziama , Arturo R. Dominguez , Jennifer H. Cao","doi":"10.1016/j.jtos.2025.05.002","DOIUrl":"10.1016/j.jtos.2025.05.002","url":null,"abstract":"<div><h3>Objective</h3><div>To evaluate the efficacy of Janus kinase inhibitor (JAKi) therapy in managing cicatrizing conjunctivitis associated with ocular cicatricial pemphigoid (OCP) and mucous membrane pemphigoid with ocular involvement (ocMMP).</div></div><div><h3>Methods</h3><div>Retrospective chart review of patients with cicatrizing conjunctivitis secondary to OCP or ocMMP who underwent treatment with JAKi at a tertiary academic medical center from August 2015 to November 2024 for minimum follow-up of six months. Collected data included demographics, Foster stage of cicatrization, and treatment course.</div></div><div><h3>Results</h3><div>Thirty-two patients met inclusion criteria: 23 (71.9 %) with OCP and 9 (28.1 %) with ocMMP. 96.9 % of patients demonstrated clinical improvement within twelve months of treatment initiation. Best response achieved were as follows: 1 (3.1 %) no response, 17 (53.1 %) partial response, 14 (43.8 %) complete remission, and 12 (37.5 %) steroid-free complete remission. The mean time to partial response, complete remission, steroid-free complete remission was 3.1 ± 1.8 (range, 0.9–8.3), 7.8 ± 3.3 months (range, 2.3–14.7 months), and 10.3 ± 7.4 months, (range, 2.3–31.4 months), respectively. Relapse in disease activity occurred in 8/32 (25.0 %) of patients. Side effects occurred in 8/32 (25.0 %) of patients. Four patients (12.5 %) discontinued therapy due to severe adverse events, including transient ischemic attack, pulmonary embolism, pyelonephritis, and cholecystitis. There was a significant association between lower Foster cicatrization stages and achieving remission (U = 630.0, p = 0.0036), with a rank-biserial correlation of 0.72.</div></div><div><h3>Conclusions</h3><div>JAK inhibitor therapy demonstrates efficacy in the management of recalcitrant cicatrizing conjunctivitis associated with pemphigoid. These findings highlight JAK inhibitors as a promising therapeutic option for refractory cases.</div></div>","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":"38 ","pages":"Pages 1-7"},"PeriodicalIF":5.9,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144082988","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 : 2025-10-01Epub Date: 2025-08-21DOI: 10.1016/j.jtos.2025.08.006
P. Ewen King-Smith , Carolyn G. Begley , Richard J. Braun
Two models of meibum and the TFLL are proposed. The first model is based on a reanalysis of x-ray studies which show the predominance of 11 nm thick lamellae above 30 °C, but below 30 °C, 5 nm thick lamellae predominate. By analogy to skin lipid, we denote these the long (LPP) and short period phase (SPP), respectively. In the model, the SPP lamellae are interdigitated bilayers of cholesteryl esters (CEs) oriented towards one surface and wax esters (WEs) oriented towards the other surface, with the long interdigitated CE and WE chains tilted. These lamellae are stacked with the same polarity, e.g., CE surface uppermost. At ocular surface temperature, the polarity of alternate layers is reversed, forming the LPP. This doubles the periodicity, but the tilt of the LPP long chains is reduced to render the periodicity more than twice the SPP. The model is consistent with changes in meibum near 30 °C found in calorimetry, viscoelasticity, infrared spectra, birefringence, reflectance, and high resolution images of meibum spread on saline. A secondary model explains the finding that most long saturated chains in CEs and WEs are branched. We propose a ‘bump and hollow’ model where a ‘bump’ is a branch on a WE chain fitting into a ‘hollow’, the linking oxygen atom in a neighboring CE chain; likewise, a bump on a CE chain fits a hollow on a WE chain. We aim to stimulate further development of lipid layer models, including the role of other molecules, to aid understanding of dry eye disease (DED).
{"title":"Two models of the structures of the lamellae in human meibum and the tear film lipid layer, TFLL","authors":"P. Ewen King-Smith , Carolyn G. Begley , Richard J. Braun","doi":"10.1016/j.jtos.2025.08.006","DOIUrl":"10.1016/j.jtos.2025.08.006","url":null,"abstract":"<div><div>Two models of meibum and the TFLL are proposed. The first model is based on a reanalysis of x-ray studies which show the predominance of 11 nm thick lamellae above 30 °C, but below 30 °C, 5 nm thick lamellae predominate. By analogy to skin lipid, we denote these the long (LPP) and short period phase (SPP), respectively. In the model, the SPP lamellae are interdigitated bilayers of cholesteryl esters (CEs) oriented towards one surface and wax esters (WEs) oriented towards the other surface, with the long interdigitated CE and WE chains tilted. These lamellae are stacked with the same polarity, e.g., CE surface uppermost. At ocular surface temperature, the polarity of alternate layers is reversed, forming the LPP. This doubles the periodicity, but the tilt of the LPP long chains is reduced to render the periodicity more than twice the SPP. The model is consistent with changes in meibum near 30 °C found in calorimetry, viscoelasticity, infrared spectra, birefringence, reflectance, and high resolution images of meibum spread on saline. A secondary model explains the finding that most long saturated chains in CEs and WEs are branched. We propose a ‘bump and hollow’ model where a ‘bump’ is a branch on a WE chain fitting into a ‘hollow’, the linking oxygen atom in a neighboring CE chain; likewise, a bump on a CE chain fits a hollow on a WE chain. We aim to stimulate further development of lipid layer models, including the role of other molecules, to aid understanding of dry eye disease (DED).</div></div>","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":"38 ","pages":"Pages 251-259"},"PeriodicalIF":5.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144899255","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-01Epub Date: 2025-05-30DOI: 10.1016/j.jtos.2025.05.010
Hassan Mansoor , Isabelle Xin Yu Lee , Chang Liu , Mingyi Yu , Charmaine Jan Li Toh , Victor Wei-Tsu Hsu , Fengyi Liu , Daqian Lu , Thomas Chuen Lam , Hong Chang Tan , Lei Zhou , Yu-Chi Liu
Purpose
To investigate the efficacy of oral fenofibrate in the amelioration of ocular surface inflammation in diabetes mellitus (DM).
Methods
In this open-label interventional study, 41 participants with type 2 DM received oral fenofibrate for 30 days. Forty age-matched healthy controls were recruited. Ocular surface objective and subjective assessment, in-vivo confocal microscopy (IVCM) imaging and quantification for corneal dendritic cells (DCs), epithelium and neuromas were performed. Tear inflammatory markers and proteomics were analyzed with enzyme-linked immunosorbent assay (ELISA) and Data Independent Acquisition experiments before and after treatment.
Results
Oral fenofibrate treatment significantly improved tear film breakup time (p = 0.004), corneal staining evaluated with National Eye Institute-Corneal Fluorescein Staining scores (p = 0.005), and ocular surface symptoms assessed with the Ocular Surface Disease Index scores (p = 0.003), in DM patients. On IVCM, fenofibrate significantly reduced mean DC area (p = 0.01) and mean DC density (p = 0.02), while increasing mean DC elongation (p = 0.004) and length (p = 0.01), suggesting less DC activities. Fenofibrate also significantly increased corneal epithelial cell density (p = 0.04). 192 tear proteins were significantly altered after treatment. Fenofibrate significantly up-regulated the expression of anti-inflammatory interleukin-1 receptor antagonist, while significantly reduced the concentrations of pro-inflammatory and inflammatory proteins, including tumour necrosis factor α, nuclear factor kappa B, complement 4 B, cytochrome B5 Type A, and cytochrome B5 Type B (all p < 0.05) in tears, via regulation of tricarboxylic acid cycle, oxidative phosphorylation and liver X receptor/retinoid X receptor activation.
Conclusion
This first clinical trial demonstrated that oral fenofibrate ameliorates diabetic ocular surface inflammation, providing a novel therapeutic option for diabetic keratopathy.
{"title":"Fenofibrate ameliorates ocular surface inflammation in diabetic keratopathy","authors":"Hassan Mansoor , Isabelle Xin Yu Lee , Chang Liu , Mingyi Yu , Charmaine Jan Li Toh , Victor Wei-Tsu Hsu , Fengyi Liu , Daqian Lu , Thomas Chuen Lam , Hong Chang Tan , Lei Zhou , Yu-Chi Liu","doi":"10.1016/j.jtos.2025.05.010","DOIUrl":"10.1016/j.jtos.2025.05.010","url":null,"abstract":"<div><h3>Purpose</h3><div>To investigate the efficacy of oral fenofibrate in the amelioration of ocular surface inflammation in diabetes mellitus (DM).</div></div><div><h3>Methods</h3><div>In this open-label interventional study, 41 participants with type 2 DM received oral fenofibrate for 30 days. Forty age-matched healthy controls were recruited. Ocular surface objective and subjective assessment, in-vivo confocal microscopy (IVCM) imaging and quantification for corneal dendritic cells (DCs), epithelium and neuromas were performed. Tear inflammatory markers and proteomics were analyzed with enzyme-linked immunosorbent assay (ELISA) and Data Independent Acquisition experiments before and after treatment.</div></div><div><h3>Results</h3><div>Oral fenofibrate treatment significantly improved tear film breakup time (p = 0.004), corneal staining evaluated with National Eye Institute-Corneal Fluorescein Staining scores (p = 0.005), and ocular surface symptoms assessed with the Ocular Surface Disease Index scores (p = 0.003), in DM patients. On IVCM, fenofibrate significantly reduced mean DC area (p = 0.01) and mean DC density (p = 0.02), while increasing mean DC elongation (p = 0.004) and length (p = 0.01), suggesting less DC activities. Fenofibrate also significantly increased corneal epithelial cell density (p = 0.04). 192 tear proteins were significantly altered after treatment. Fenofibrate significantly up-regulated the expression of anti-inflammatory interleukin-1 receptor antagonist, while significantly reduced the concentrations of pro-inflammatory and inflammatory proteins, including tumour necrosis factor α, nuclear factor kappa B, complement 4 B, cytochrome B5 Type A, and cytochrome B5 Type B (all p < 0.05) in tears, via regulation of tricarboxylic acid cycle, oxidative phosphorylation and liver X receptor/retinoid X receptor activation.</div></div><div><h3>Conclusion</h3><div>This first clinical trial demonstrated that oral fenofibrate ameliorates diabetic ocular surface inflammation, providing a novel therapeutic option for diabetic keratopathy.</div></div>","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":"38 ","pages":"Pages 31-40"},"PeriodicalIF":5.9,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144195330","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 : 2025-10-01Epub 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":"2025-10-01","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 : 2025-10-01Epub Date: 2025-10-24DOI: 10.1016/j.jtos.2025.10.009
Sezen Karakus , Jane Jin Huang , Meltem Yashar , Meron Haile , Ugur Tunc , Claudia Viton , Stefan Cehan , Pranav Kotamraju , Cynthia Wang , Brittany L. Adler , Tae H. Chung
Purpose
Postural Orthostatic Tachycardia Syndrome (POTS), an autonomic nervous system dysfunction, is frequently associated with ocular symptoms including pain and dryness. This study aimed to characterize ocular surface findings in POTS patients to clarify whether these symptoms reflect classic dry eye disease or altered sensory processing related to autonomic dysfunction.
Methods
A retrospective observational study was conducted on patients with confirmed POTS who underwent standardized ocular surface evaluations at a tertiary academic center between 2019 and 2024. Demographics and medical history were extracted from records. Assessments included pain ratings (0–10 Likert scale), proparacaine response, Schirmer testing, ocular staining score (OSS), and in vivo confocal microscopy (IVCM) when available.
Results
Forty-three patients (39 females; mean age 45.1 ± 14.0 years) were included. Thirty-eight reported ocular pain and dryness. Among 21 patients with recorded pain scores, the median (IQR) was 5 (4), reduced to 4 (4.5) after proparacaine. Median Schirmer score was 5 mm (IQR 27), with 13 patients ≤5 mm. Median OSS was 0 (IQR 2), with only 4 patients showing OSS>1 with improved symptoms after proparacaine, suggesting neuropathic etiology in 34 patients. IVCM, available in six cases, revealed reduced nerve density and microneuromas. Migraine was the most common comorbidity (76.7 %) and was strongly associated with pain without staining (OR = 15.0; 95 % CI 2.65–85.0; p = 0.002).
Conclusions
POTS patients frequently report ocular pain and dryness, yet objective signs of dry eye are uncommon. These findings underscore the need for ocular surface staining to distinguish dry eye disease from neuropathic ocular pain, suggesting that altered corneal nerve function in autonomic dysfunction may drive symptoms.
目的体位性站立性心动过速综合征（POTS）是一种自主神经系统功能障碍，常伴有眼部症状，包括疼痛和干燥。本研究旨在描述POTS患者的眼表表现，以阐明这些症状是否反映了典型的干眼病或与自主神经功能障碍相关的感觉处理改变。方法对2019 - 2024年在某三级学术中心进行标准化眼表评估的确诊POTS患者进行回顾性观察研究。从记录中提取人口统计和病史。评估包括疼痛评分（0-10李克特量表）、丙帕卡因反应、Schirmer试验、眼染色评分（OSS）和体内共聚焦显微镜（IVCM）（如果有的话）。结果纳入43例患者，其中女性39例，平均年龄45.1±14.0岁。38人报告眼部疼痛和干涩。在21例有疼痛评分记录的患者中，中位数（IQR）为5(4)，经丙帕卡因后降至4（4.5）。中位Schirmer评分为5 mm (IQR 27)， 13例患者≤5 mm。中位OSS为0 (IQR 2)，只有4例患者出现OSS>；1例患者经丙帕卡因后症状改善，提示34例患者的病因为神经性病变。6例IVCM显示神经密度降低和微神经瘤。偏头痛是最常见的合并症（76.7%），与无染色疼痛密切相关（OR = 15.0; 95% CI 2.65-85.0; p = 0.002）。结论斑点患者常报告眼部疼痛和干涩，但干眼的客观体征并不常见。这些发现强调了通过眼表染色来区分干眼病和神经性眼痛的必要性，表明自主神经功能障碍导致的角膜神经功能改变可能驱动症状。
{"title":"Eye pain and ocular surface characteristics in Postural Orthostatic Tachycardia Syndrome (POTS): The role of autonomic dysfunction","authors":"Sezen Karakus , Jane Jin Huang , Meltem Yashar , Meron Haile , Ugur Tunc , Claudia Viton , Stefan Cehan , Pranav Kotamraju , Cynthia Wang , Brittany L. Adler , Tae H. Chung","doi":"10.1016/j.jtos.2025.10.009","DOIUrl":"10.1016/j.jtos.2025.10.009","url":null,"abstract":"<div><h3>Purpose</h3><div>Postural Orthostatic Tachycardia Syndrome (POTS), an autonomic nervous system dysfunction, is frequently associated with ocular symptoms including pain and dryness. This study aimed to characterize ocular surface findings in POTS patients to clarify whether these symptoms reflect classic dry eye disease or altered sensory processing related to autonomic dysfunction.</div></div><div><h3>Methods</h3><div>A retrospective observational study was conducted on patients with confirmed POTS who underwent standardized ocular surface evaluations at a tertiary academic center between 2019 and 2024. Demographics and medical history were extracted from records. Assessments included pain ratings (0–10 Likert scale), proparacaine response, Schirmer testing, ocular staining score (OSS), and in vivo confocal microscopy (IVCM) when available.</div></div><div><h3>Results</h3><div>Forty-three patients (39 females; mean age 45.1 ± 14.0 years) were included. Thirty-eight reported ocular pain and dryness. Among 21 patients with recorded pain scores, the median (IQR) was 5 (4), reduced to 4 (4.5) after proparacaine. Median Schirmer score was 5 mm (IQR 27), with 13 patients ≤5 mm. Median OSS was 0 (IQR 2), with only 4 patients showing OSS>1 with improved symptoms after proparacaine, suggesting neuropathic etiology in 34 patients. IVCM, available in six cases, revealed reduced nerve density and microneuromas. Migraine was the most common comorbidity (76.7 %) and was strongly associated with pain without staining (OR = 15.0; 95 % CI 2.65–85.0; p = 0.002).</div></div><div><h3>Conclusions</h3><div>POTS patients frequently report ocular pain and dryness, yet objective signs of dry eye are uncommon. These findings underscore the need for ocular surface staining to distinguish dry eye disease from neuropathic ocular pain, suggesting that altered corneal nerve function in autonomic dysfunction may drive symptoms.</div></div>","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":"38 ","pages":"Pages 359-364"},"PeriodicalIF":5.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145382684","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-01Epub Date: 2025-04-07DOI: 10.1016/j.jtos.2025.03.008
John K.G. Dart , Vincenzo Papa , Paolo Rama , Karl Anders Knutsson , Saj Ahmad , Scott Hau , Sara Sanchez , Antonella Franch , Federica Birattari , Pia Leon , Adriano Fasolo , Ewa Mrukwa-Kominek , Katarzyna Jadczyk-Sorek , Fiona Carley , Hossain Parwez , Darwin C. Minassian
Purpose
To compare Acanthamoeba keratitis (AK) outcomes for treatment delivered using a detailed protocol versus physician's individualised treatment.
Methods
This double cohort study compared the outcomes of these different delivery methods for PHMB 0.02 % and diamidine 0.1 % dual therapy. The primary outcome was the medical cure rate without surgery within 12 months (MCR_12) and the secondary was visual acuity. Any change of treatment, any surgery, or treatment for >12 months was a failure. Outcomes were both unadjusted and adjusted, using multivariable analysis, for baseline differences affecting outcomes. Patients were from two centres in Milan and London treated at different times; the individualised cohort (1991–2012) and per-protocol cohort (2017–2021).
Results
The individualised cohort included 96 and the per-protocol 47 patients. Both unadjusted and adjusted results were similar. The unadjusted outcomes for both centres combined showed significantly improved outcomes for per-protocol treatment with a 1.59-fold improvement in MCR_12 (95 % CI 1.40–1.80, p < 0.001) and a 2.1-fold increase in visual acuity ≥20/25 (95 % CI 1.34–3.29, p < 0.001). Amongst potential confounding factors examined, neither baseline AK disease stage, treatment centre nor the type of diamidine significantly influenced outcomes.
Conclusions
This study shows significant advantages for the use of protocol delivered versus individualised treatment for AK. The use of evidence-based treatment delivery protocols, like the one used here for AK, might improve outcomes for all causes of microbial keratitis and could offer practitioners and patients the benefit of having an easy-to-follow drug delivery protocol, with known outcomes.
目的：比较棘阿米巴角膜炎（AK）的治疗结果提供了一个详细的方案和医生的个体化治疗。方法：本双队列研究比较了0.02% PHMB和0.1%二胺双重治疗的不同给药方式的结果。主要观察指标为12个月内不手术治愈率（MCR_12），次要观察指标为视力。任何治疗方法的改变，任何手术，或长达12个月的治疗都是失败的。采用多变量分析，对影响结果的基线差异进行了未调整和调整。来自米兰和伦敦两个中心的患者在不同时间接受治疗；个体化队列（1991-2012）和按方案队列（2017-2021）。结果：个体化队列96例，按方案47例。未调整和调整后的结果相似。两个中心未经调整的合并结果显示，按方案治疗的结果显著改善，MCR_12改善1.59倍（95% CI 1.40 - 1.80, p < 0.001），视力≥20/25增加2.1倍（95% CI 1.34 - 3.29, p < 0.001）。在检查的潜在混杂因素中，基线AK疾病分期、治疗中心和二胺类型均未显著影响结果。结论：这项研究显示了使用方案传递与个性化治疗AK的显著优势。使用循证治疗方案，如这里使用的AK，可能会改善所有原因的微生物角膜炎的结果，并可以为医生和患者提供一个易于遵循的药物给药方案，已知的结果。
{"title":"Acanthamoeba keratitis treatment outcomes compared for drug delivery by protocol versus physician's individualised treatment","authors":"John K.G. Dart , Vincenzo Papa , Paolo Rama , Karl Anders Knutsson , Saj Ahmad , Scott Hau , Sara Sanchez , Antonella Franch , Federica Birattari , Pia Leon , Adriano Fasolo , Ewa Mrukwa-Kominek , Katarzyna Jadczyk-Sorek , Fiona Carley , Hossain Parwez , Darwin C. Minassian","doi":"10.1016/j.jtos.2025.03.008","DOIUrl":"10.1016/j.jtos.2025.03.008","url":null,"abstract":"<div><h3>Purpose</h3><div>To compare Acanthamoeba keratitis (AK) outcomes for treatment delivered using a detailed protocol versus physician's individualised treatment.</div></div><div><h3>Methods</h3><div>This double cohort study compared the outcomes of these different delivery methods for PHMB 0.02 % and diamidine 0.1 % dual therapy. The primary outcome was the medical cure rate without surgery within 12 months (MCR_12) and the secondary was visual acuity. Any change of treatment, any surgery, or treatment for >12 months was a failure. Outcomes were both unadjusted and adjusted, using multivariable analysis, for baseline differences affecting outcomes. Patients were from two centres in Milan and London treated at different times; the individualised cohort (1991–2012) and per-protocol cohort (2017–2021).</div></div><div><h3>Results</h3><div>The individualised cohort included 96 and the per-protocol 47 patients. Both unadjusted and adjusted results were similar. The unadjusted outcomes for both centres combined showed significantly improved outcomes for per-protocol treatment with a 1.59-fold improvement in MCR_12 (95 % CI 1.40–1.80, p < 0.001) and a 2.1-fold increase in visual acuity ≥20/25 (95 % CI 1.34–3.29, p < 0.001). Amongst potential confounding factors examined, neither baseline AK disease stage, treatment centre nor the type of diamidine significantly influenced outcomes.</div></div><div><h3>Conclusions</h3><div>This study shows significant advantages for the use of protocol delivered versus individualised treatment for AK. The use of evidence-based treatment delivery protocols, like the one used here for AK, might improve outcomes for all causes of microbial keratitis and could offer practitioners and patients the benefit of having an easy-to-follow drug delivery protocol, with known outcomes.</div></div>","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":"38 ","pages":"Pages 132-141"},"PeriodicalIF":5.9,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144002474","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 : 2025-10-01Epub Date: 2025-10-13DOI: 10.1016/j.jtos.2025.10.002
Jai Paris , Carmelo Macri , Abdullah I. Almater , James Slattery , Dinesh Selva
Ocular involvement in Stevens-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TENS) is common and can result in severe acute inflammation and long-term complications. Early intervention with amniotic membrane transplantation (AMT) is essential to preserve long term ocular surface integrity and function. This review aimed to evaluate and compare the different surgical techniques to AMT in the acute phase of SJS/TENS, covering sutured, glued, and sutureless/glueless approaches. A systematic search of PubMed, MEDLINE, Embase, Scopus, Cochrane, Google Scholar, and reference lists identified 630 articles, with 27 studies meeting inclusion criteria. Sutured AMT remains the most commonly used method due to its ability to provide comprehensive ocular surface coverage, however is time-consuming and often requires general anaesthesia. Glued AMT, using fibrin or cyanoacrylate adhesive, offers a faster, less invasive alternative suitable for bedside application, though evidence in SJS/TENS is limited. Sutureless/glueless options such as the Prokera® enable rapid deployment and patient comfort but do not provide full ocular surface protection and should only be usedas adjuncts. Hybrid glued approaches with limited suturing may be appropriate for extensive coverage with bedside application. Overall, the choice of technique depends on the extent of ocular involvement, patient stability, and available resources. Further studies are needed to directly compare outcomes across different AMT approaches in acute ocular SJS/TENS.
{"title":"Amniotic membrane transplantation techniques in acute ocular Stevens-Johnson syndrome and toxic epidermal necrolysis: A systematic review","authors":"Jai Paris , Carmelo Macri , Abdullah I. Almater , James Slattery , Dinesh Selva","doi":"10.1016/j.jtos.2025.10.002","DOIUrl":"10.1016/j.jtos.2025.10.002","url":null,"abstract":"<div><div>Ocular involvement in Stevens-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TENS) is common and can result in severe acute inflammation and long-term complications. Early intervention with amniotic membrane transplantation (AMT) is essential to preserve long term ocular surface integrity and function. This review aimed to evaluate and compare the different surgical techniques to AMT in the acute phase of SJS/TENS, covering sutured, glued, and sutureless/glueless approaches. A systematic search of PubMed, MEDLINE, Embase, Scopus, Cochrane, Google Scholar, and reference lists identified 630 articles, with 27 studies meeting inclusion criteria. Sutured AMT remains the most commonly used method due to its ability to provide comprehensive ocular surface coverage, however is time-consuming and often requires general anaesthesia. Glued AMT, using fibrin or cyanoacrylate adhesive, offers a faster, less invasive alternative suitable for bedside application, though evidence in SJS/TENS is limited. Sutureless/glueless options such as the Prokera® enable rapid deployment and patient comfort but do not provide full ocular surface protection and should only be usedas adjuncts. Hybrid glued approaches with limited suturing may be appropriate for extensive coverage with bedside application. Overall, the choice of technique depends on the extent of ocular involvement, patient stability, and available resources. Further studies are needed to directly compare outcomes across different AMT approaches in acute ocular SJS/TENS.</div></div>","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":"38 ","pages":"Pages 337-358"},"PeriodicalIF":5.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145305134","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-01Epub Date: 2025-09-24DOI: 10.1016/j.jtos.2025.09.001
N.V. Prajna , N. Radhakrishnan , Prajna Lalitha , Revathi Rajaraman , Sarah Abdelrahman , Benjamin F. Arnold , Thomas M. Lietman , Jennifer Rose-Nussbaumer , Alejandro Arboleda
Purpose
To identify clinical characteristics that predict vision-related quality of life (QoL) in patients with fungal keratitis three months after treatment.
Methods
Patients with fungal keratitis enrolled in the Cross-Linking Assisted Infection Reduction trial were treated with topical natamycin 5 % or amphotericin 0.15 %, with or without adjuvant corneal cross-linking (CXL). Demographic data, ulcer characteristics, clinical course, and responses to the Indian Visual Function Questionnaire (IND-VFQ) were collected at baseline and follow-up. Logistic regression models were used to assess factors associated with patient-reported vision-related QoL at three months. Analyses included the average IND-VFQ score as well as Rasch-derived subscale scores for vision-specific mobility, activity limitation, psychosocial impact, and visual symptoms.
Results
Of 111 participants enrolled, 86 had complete data at both timepoints. Multivariable models identified baseline IND-VFQ score, scar size, and presence of hypopyon as significant predictors of 3-month IND-VFQ scores. A 1-point change in best spectacle corrected visual acuity is correlated with a 13.4-point change in the opposite direction in average IND-VFQ (P=0.001). Patients with adverse events requiring surgery had lower 3-month IND-VFQ scores than those managed medically (P=0.001). Ulcer characteristics including location, depth, symptom duration, repeat culture positivity, organism type, and fungal genus were not associated with final IND-VFQ scores.
Conclusions
Vision-related QoL after fungal keratitis is significantly influenced by change in visual acuity, need for surgical intervention, and select baseline factors including scar size, initial IND-VFQ score, and presence of hypopyon. Vision-related QoL did not differ by antifungal treatment or adjuvant CXL use.
{"title":"Predictors of vision-related quality of life in patients treated for filamentous fungal keratitis","authors":"N.V. Prajna , N. Radhakrishnan , Prajna Lalitha , Revathi Rajaraman , Sarah Abdelrahman , Benjamin F. Arnold , Thomas M. Lietman , Jennifer Rose-Nussbaumer , Alejandro Arboleda","doi":"10.1016/j.jtos.2025.09.001","DOIUrl":"10.1016/j.jtos.2025.09.001","url":null,"abstract":"<div><h3>Purpose</h3><div>To identify clinical characteristics that predict vision-related quality of life (QoL) in patients with fungal keratitis three months after treatment.</div></div><div><h3>Methods</h3><div>Patients with fungal keratitis enrolled in the Cross-Linking Assisted Infection Reduction trial were treated with topical natamycin 5 % or amphotericin 0.15 %, with or without adjuvant corneal cross-linking (CXL). Demographic data, ulcer characteristics, clinical course, and responses to the Indian Visual Function Questionnaire (IND-VFQ) were collected at baseline and follow-up. Logistic regression models were used to assess factors associated with patient-reported vision-related QoL at three months. Analyses included the average IND-VFQ score as well as Rasch-derived subscale scores for vision-specific mobility, activity limitation, psychosocial impact, and visual symptoms.</div></div><div><h3>Results</h3><div>Of 111 participants enrolled, 86 had complete data at both timepoints. Multivariable models identified baseline IND-VFQ score, scar size, and presence of hypopyon as significant predictors of 3-month IND-VFQ scores. A 1-point change in best spectacle corrected visual acuity is correlated with a 13.4-point change in the opposite direction in average IND-VFQ (P=0.001). Patients with adverse events requiring surgery had lower 3-month IND-VFQ scores than those managed medically (P=0.001). Ulcer characteristics including location, depth, symptom duration, repeat culture positivity, organism type, and fungal genus were not associated with final IND-VFQ scores.</div></div><div><h3>Conclusions</h3><div>Vision-related QoL after fungal keratitis is significantly influenced by change in visual acuity, need for surgical intervention, and select baseline factors including scar size, initial IND-VFQ score, and presence of hypopyon. Vision-related QoL did not differ by antifungal treatment or adjuvant CXL use.</div></div>","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":"38 ","pages":"Pages 319-323"},"PeriodicalIF":5.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145180773","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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