Pub Date : 2025-08-27DOI: 10.1016/j.jtos.2025.08.008
Ke Yan , Yiran Yang , Yi Han , Yuhan Zhang , Tong Zhou , Wenxin Sun , Ruochen Wang , Zhaolin Liu , Qinghe Zhang , Linfangzi Zhu , Meidi Tan , Caihong Huang , Jiaoyue Hu , Qiuping Liu , Zhaoqiang Zhang , Zuguo Liu
Corneal neovascularization (CNV) is a leading cause of vision impairment, with existing therapeutic options offering limited efficacy. This study presents L009, a novel antiangiogenic agent derived from the Kringle 5 domain of human plasminogen, specifically a heptapeptide, designed to treat CNV. In preclinical models, L009 demonstrated substantial efficacy by markedly inhibiting endothelial cell proliferation and migration, reducing vascular permeability, and maintaining ocular safety. Mechanistically, L009 exerts its effects by upregulating tumor necrosis factor superfamily member 15 (TNFSF15), downregulating vascular endothelial growth factor receptor 2 (VEGFR2), and increasing the expression of soluble VEGFR1. These actions restore vascular homeostasis and enhance vascular stability through the upregulation of the tight junction protein VE-cadherin. By specifically targeting the TNFSF15-VEGF axis, L009 offers a distinctive therapeutic approach, differentiating it from conventional anti-VEGF therapies. Its dual action of anti-angiogenesis and promotion of vascular stability highlights its potential as a next-generation treatment for CNV. Further investigation into its long-term efficacy and potential for synergy with existing therapies is warranted.
{"title":"L009 peptide as a novel antiangiogenic agent for corneal neovascularization via regulation of the TNFSF15-VEGF axis","authors":"Ke Yan , Yiran Yang , Yi Han , Yuhan Zhang , Tong Zhou , Wenxin Sun , Ruochen Wang , Zhaolin Liu , Qinghe Zhang , Linfangzi Zhu , Meidi Tan , Caihong Huang , Jiaoyue Hu , Qiuping Liu , Zhaoqiang Zhang , Zuguo Liu","doi":"10.1016/j.jtos.2025.08.008","DOIUrl":"10.1016/j.jtos.2025.08.008","url":null,"abstract":"<div><div>Corneal neovascularization (CNV) is a leading cause of vision impairment, with existing therapeutic options offering limited efficacy. This study presents L009, a novel antiangiogenic agent derived from the Kringle 5 domain of human plasminogen, specifically a heptapeptide, designed to treat CNV. In preclinical models, L009 demonstrated substantial efficacy by markedly inhibiting endothelial cell proliferation and migration, reducing vascular permeability, and maintaining ocular safety. Mechanistically, L009 exerts its effects by upregulating tumor necrosis factor superfamily member 15 (TNFSF15), downregulating vascular endothelial growth factor receptor 2 (VEGFR2), and increasing the expression of soluble VEGFR1. These actions restore vascular homeostasis and enhance vascular stability through the upregulation of the tight junction protein VE-cadherin. By specifically targeting the TNFSF15-VEGF axis, L009 offers a distinctive therapeutic approach, differentiating it from conventional anti-VEGF therapies. Its dual action of anti-angiogenesis and promotion of vascular stability highlights its potential as a next-generation treatment for CNV. Further investigation into its long-term efficacy and potential for synergy with existing therapies is warranted.</div></div>","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":"38 ","pages":"Pages 274-289"},"PeriodicalIF":5.6,"publicationDate":"2025-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144914097","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 : 2025-08-21DOI: 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":"2025-08-21","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 : 2025-08-20DOI: 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.
{"title":"IVCM image analysis for limbal stem cell deficiency: quantitative diagnostics of the corneal epithelium post-transplant recovery","authors":"Patrick Parkinson , Irina Makarenko , Oliver J. Baylis , Gustavo S. Figueiredo , Majlinda Lako , Anvar Shukurov , Francisco C. Figueiredo , Laura E. Wadkin","doi":"10.1016/j.jtos.2025.08.005","DOIUrl":"10.1016/j.jtos.2025.08.005","url":null,"abstract":"<div><h3>Purpose</h3><div>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 <em>ex-vivo</em> 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.</div></div><div><h3>Methods</h3><div>We consider the <em>in-vivo</em> 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.</div></div><div><h3>Results</h3><div>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.</div></div><div><h3>Conclusion</h3><div>Cell area is a sensitive and easily accessible marker of corneal epithelial recovery in LSCD patients post-LSC transplant.</div></div>","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":"38 ","pages":"Pages 266-273"},"PeriodicalIF":5.6,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144899294","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 : 2025-08-19DOI: 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
{"title":"Economic burden of keratitis patients with inpatient care: a nationwide, multicenter registry study","authors":"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","doi":"10.1016/j.jtos.2025.08.007","DOIUrl":"10.1016/j.jtos.2025.08.007","url":null,"abstract":"","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":"38 ","pages":"Pages 262-265"},"PeriodicalIF":5.6,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144899125","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 : 2025-08-18DOI: 10.1016/j.jtos.2025.08.004
Gary D. Novack
{"title":"Pipeline: Patient, physician and developer view of drugs vs. devices","authors":"Gary D. Novack","doi":"10.1016/j.jtos.2025.08.004","DOIUrl":"10.1016/j.jtos.2025.08.004","url":null,"abstract":"","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":"38 ","pages":"Pages 260-261"},"PeriodicalIF":5.6,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144902470","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 : 2025-08-18DOI: 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":"2025-08-18","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 : 2025-08-14DOI: 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.
{"title":"Exploration of imaging and molecular biomarkers for differentiation of neuropathic corneal pain from dry eye syndrome","authors":"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","doi":"10.1016/j.jtos.2025.08.002","DOIUrl":"10.1016/j.jtos.2025.08.002","url":null,"abstract":"<div><h3>Purpose</h3><div>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.</div></div><div><h3>Methods</h3><div>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.</div></div><div><h3>Results</h3><div>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.</div></div><div><h3>Conclusion</h3><div>NCP patients present with different imaging features, clinical characteristics and proteomic profiles, compared with DED patients. These can be used as differentiating indicators.</div></div>","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":"38 ","pages":"Pages 230-241"},"PeriodicalIF":5.6,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144862758","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 : 2025-08-10DOI: 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.
{"title":"Differences in pre-surgical baseline tear proteome are associated with persistent post-refractive surgery pain","authors":"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","doi":"10.1016/j.jtos.2025.08.001","DOIUrl":"10.1016/j.jtos.2025.08.001","url":null,"abstract":"<div><h3>Purpose</h3><div>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.</div></div><div><h3>Methods</h3><div>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.</div></div><div><h3>Results</h3><div>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.</div></div><div><h3>Conclusion</h3><div>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.</div></div>","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":"38 ","pages":"Pages 219-229"},"PeriodicalIF":5.6,"publicationDate":"2025-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144839577","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 : 2025-07-30DOI: 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.
{"title":"Antibiotic resistance of Pseudomonas aeruginosa from ocular samples in Canada: a 25-year analysis","authors":"Alfonso Iovieno , Barbara Burgos-Blasco , Derek Chan , Sean Ling , Simon Holland , Sonia N. Yeung","doi":"10.1016/j.jtos.2025.07.011","DOIUrl":"10.1016/j.jtos.2025.07.011","url":null,"abstract":"<div><h3>Objective</h3><div>To identify trends in antibiotic resistance patterns of Pseudomonas aeruginosa (PA) over a multi-decade period and analyse clinical outcomes.</div></div><div><h3>Methods</h3><div>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.</div></div><div><h3>Results</h3><div>321 ocular isolates of <em>Pseudomonas</em> 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.</div></div><div><h3>Conclusions</h3><div>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.</div></div>","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":"38 ","pages":"Pages 187-194"},"PeriodicalIF":5.6,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144765936","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 : 2025-07-30DOI: 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.
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