Ocular SurfacePub 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
{"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}
Ocular SurfacePub 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
{"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}
Ocular SurfacePub 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
{"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}
Ocular SurfacePub 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
{"title":"Topical pharmacologic treatments for dry eye disease: A systematic review","authors":"Louis Tong , Zuguo Liu , Afsun Şahin , Koray Gümüş , Elisabeth M. Messmer , José M. Benítez-del-Castillo , Marc Labetoulle , Clara C. Chan , Laura M. Periman","doi":"10.1016/j.jtos.2025.07.010","DOIUrl":"10.1016/j.jtos.2025.07.010","url":null,"abstract":"<div><h3>Background</h3><div>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.</div></div><div><h3>Methods</h3><div>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.</div></div><div><h3>Results</h3><div>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.</div></div><div><h3>Conclusions</h3><div>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.</div></div>","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":"38 ","pages":"Pages 302-317"},"PeriodicalIF":5.6,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144765938","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}
Ocular SurfacePub Date : 2025-07-24DOI: 10.1016/j.jtos.2025.07.008
Naman Gupta, Giovanni LoGrasso, Linda D. Hazlett, Shunbin Xu
{"title":"New insight into the neuroimmune interplay in Pseudomonas aeruginosa keratitis","authors":"Naman Gupta, Giovanni LoGrasso, Linda D. Hazlett, Shunbin Xu","doi":"10.1016/j.jtos.2025.07.008","DOIUrl":"10.1016/j.jtos.2025.07.008","url":null,"abstract":"<div><h3>Purpose</h3><div>This research aims to reveal the roles of the miR-183/96/182 cluster (miR-183C) in sensory neurons (SN) in the interplay of corneal sensory nerves (CSN) and myeloid cells (MC) during <em>Pseudomonas aeruginosa</em> (PA) keratitis.</div></div><div><h3>Methods</h3><div>The left corneas of SN-specific (SNS) conditional knockout (CKO) and their wild type (WT) littermates were infected with PA. CSN of these mice express RFP; MC EGFP. Confocal microscopy of corneal flatmount, myeloperoxidase (MPO) assay and plate count were performed.</div></div><div><h3>Results</h3><div>In WT mice, CSN began to degenerate at 3 h-post-infection (hpi), starting from epithelial/subepithelial layers in the central region. By 1 day-post-infection (dpi), epithelium/subepithelial CSN were nearly completely destroyed, while stromal nerves persisted. From 3 dpi, CSN were obliterated in both layers. In CKO vs WT mice, CSN density was decreased at 3 and 6 hpi; however, CNS degeneration followed a slower pace. At 3 dpi, residual large-diameter stromal CSN were better preserved.</div><div>MC were decreased in the central cornea at 3 and 6 hpi, but increased in the periphery, more prominent in CKO mice. At 12 hpi, densely packed MC formed a ring-shaped band circling a “dark” zone nearly devoid of MC, colocalizing with CSN most degenerated central area. At 1 dpi, the cornea was filled with MC; MC density was lower in CKO. CKO mice had decreased neutrophils at 1 dpi and reduced disease severity at 3 dpi.</div></div><div><h3>Conclusions</h3><div>Our results provide new insight into the neuroimmune interplay during PA keratitis. miR-183C in CSN modulates PA keratitis through regulation of neuroimmune interaction.</div></div>","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":"38 ","pages":"Pages 170-183"},"PeriodicalIF":5.6,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144719318","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}
Ocular SurfacePub Date : 2025-07-19DOI: 10.1016/j.jtos.2025.07.005
Gelila B. Yohannes , Nathan L. Scott , Wendy J. Li , Carol L. Karp
{"title":"Systemic immune checkpoint inhibitors: Successful treatment of conjunctival atypical melanocytic proliferation documented by anterior segment optical coherence tomography","authors":"Gelila B. Yohannes , Nathan L. Scott , Wendy J. Li , Carol L. Karp","doi":"10.1016/j.jtos.2025.07.005","DOIUrl":"10.1016/j.jtos.2025.07.005","url":null,"abstract":"","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":"38 ","pages":"Pages 184-186"},"PeriodicalIF":5.6,"publicationDate":"2025-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144664959","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}
Ocular SurfacePub Date : 2025-07-18DOI: 10.1016/j.jtos.2025.07.003
Juana Gallar , Stephen Pflugfelder , Anat Galor , Preeya K. Gupta , Pedram Hamrah
{"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}
Ocular SurfacePub 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
{"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}
Ocular SurfacePub 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
{"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}