Ocular Surface最新文献

{"title":"Impact of image selection on corneal nerve and dendritic cell density quantification using in vivo confocal microscopy","authors":"Jenny Roth,&nbsp;Karthikeyan Baskaran,&nbsp;Ava Dashti,&nbsp;Petros Moustardas,&nbsp;Antonio Filipe Macedo,&nbsp;Neil Lagali","doi":"10.1016/j.jtos.2026.09.005","DOIUrl":"10.1016/j.jtos.2026.09.005","url":null,"abstract":"<div><h3>Aim</h3><div>The aim of this study was to measure the impact of image selection on quantification of corneal nerve fibre length density (CNFL) and dendritic cell density (DCD) using in-vivo confocal microscopy images.</div></div><div><h3>Methods</h3><div>We used images from 80 participants (mean age 51 years; 55 female), averaging 1030 images per participant. CNFL and DCD were quantified using independently selected sets and same-image sets. Inter-grader agreement was computed using 10 or 5 images per participant (patient-level data point). Grader agreement was quantified by intraclass correlation coefficients (ICC).</div></div><div><h3>Results</h3><div>Using independently selected images, the ICC for CNFL was 0.82 with 10 images, which was significantly higher by 0.07 than with 5 images (p = 0.009). For DCD, the ICC was 0.92 with 10 images and was not significantly higher than with 5 images. Using same-image sets, the ICC for CNFL was 0.94 with both 5 and 10 images. For DCD, the ICC improved by 0.03 when 10 images were used compared with 5 images (p = 0.02).</div></div><div><h3>Conclusion</h3><div>Independent-image selection gives poorer reproducibility of CNFL and DCD than multiple graders using the same-image sets. The same-image sets yielded excellent agreement, suggesting that studies relying on a single selection of five or fewer images should be interpreted with caution, as a single selection is more prone to rater bias. Because a single set of selected images reflects real-world practice, we recommend that future studies use multiple graders, each independently selecting and grading images, with more than five images per participant where feasible.</div></div>","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":"42 ","pages":"Pages 287-294"},"PeriodicalIF":6.6,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149043131","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phase II clinical trial of cultivated oral mucosal epithelial transplantation (COMET) for patients with severe ocular surface disorders","authors":"Kojiro Imai,&nbsp;Seitaro Komai,&nbsp;Koji Kitazawa,&nbsp;Hideki Fukuoka,&nbsp;Takahiro Nakamura,&nbsp;Mayumi Ueta,&nbsp;Tsutomu Inatomi,&nbsp;Yasuko Kimura,&nbsp;Masahiro J. Go,&nbsp;Kenichiro Tanabe,&nbsp;Tatsuo Kagimura,&nbsp;Masanori Fukushima,&nbsp;Shigeru Kinoshita,&nbsp;Chie Sotozono","doi":"10.1016/j.jtos.2026.09.006","DOIUrl":"10.1016/j.jtos.2026.09.006","url":null,"abstract":"<div><h3>Purpose</h3><div>To prospectively evaluate the safety and efficacy of cultivated oral mucosal epithelial transplantation (COMET) for the treatment of severe ocular surface disorders (OSDs).</div></div><div><h3>Methods</h3><div>This phase II, nonrandomized clinical trial involved patients with severe OSDs (i.e., Stevens-Johnson syndrome, ocular cicatricial pemphigoid, or severe chemical/thermal injury) who underwent COMET at the Department of Ophthalmology, Kyoto Prefectural University of Medicine, Kyoto, Japan. Patients were assigned to three groups according to the purpose of the surgery: visual improvement (VI) group, epithelial repair (ER) group, or release of adhesion (RA) group. The primary outcomes (i.e., from before surgery to 24-weeks post COMET) were change in distance vision, change in epithelial abnormality score, and change in fornix shortening score, respectively. The secondary outcomes included any change in Ocular Surface Grading Score (OSGS) and subjective symptoms evaluated by National Eye Institute Visual Function Questionnaire-25 (NEI VFQ-25) findings. All intra- and postoperative adverse events were recorded.</div></div><div><h3>Results</h3><div>Of the 27 registered patients in this study, 22 (i.e., 14 SJS cases, 5 OCP cases, and 3 severe chemical/thermal injury cases) underwent COMET. At 24-weeks postoperative, logMAR visual acuity and the fornix shortening score were significantly improved in the VI group (11 cases, 2.2 to 1.5, p = 0.0060) and RA group (5 cases, 4.7 to 1.2, p = 0.0010), respectively. The total epithelial abnormality score improved in 50% of the ER-group patients (4 cases). All OSGS and NEI-VFQ scores improved, and no serious adverse events were observed.</div></div><div><h3>Conclusion</h3><div>COMET is safe and effective for treating severe OSDs.</div></div>","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":"42 ","pages":"Pages 295-305"},"PeriodicalIF":6.6,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149066930","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}

{"title":"Species-specific tear proteomic signatures in humans and rabbits: A DIA mass spectrometry comparative study","authors":"Sunay Kamalasanan,&nbsp;Saleh Ahmed,&nbsp;Victoria Clifton,&nbsp;Steven Safille,&nbsp;Tae Jin Lee,&nbsp;Shruti Sharma,&nbsp;Sreekala P.V. Shenoy,&nbsp;Patrick Michael McNutt,&nbsp;Ashok Sharma","doi":"10.1016/j.jtos.2026.09.004","DOIUrl":"10.1016/j.jtos.2026.09.004","url":null,"abstract":"<div><h3>Purpose</h3><div>Rabbits exhibit an exceptionally low blink frequency and a markedly prolonged tear breakup time compared with humans. These physiological differences suggest the presence of specialized tear-stabilizing mechanisms that may be reflected in the molecular composition of rabbit tear fluid. This exploratory study compared human and rabbit tear proteomes to identify shared and species-associated differences potentially relevant to tear film stability and ocular surface homeostasis.</div></div><div><h3>Methods</h3><div>Tear fluid samples were collected from 10 healthy human subjects and 10 healthy New Zealand White rabbits using Schirmer strips. Tear proteins were analyzed by liquid chromatography-tandem mass spectrometry. Orthologous proteins were mapped using the <em>biomaRt</em> package to enable comparative cross-species analysis.</div></div><div><h3>Results</h3><div>A total of 5270 human and 3876 rabbit proteins were detected across the cohorts, of which 4481 and 3514, respectively, were detected in at least 5 of 10 samples. Ortholog mapping identified 2267 human-rabbit ortholog pairs, while 2214 human and 1181 rabbit proteins remained unmatched. Human tears were enriched in proteins associated with mucosal immunity and antimicrobial defense, including lysozyme C, lactotransferrin, lipocalin-1, lacritin, and immunoglobulins. In contrast, rabbit tears showed enrichment of proteins associated with lipid handling, antioxidant defense, and epithelial maintenance, including lipocalin-related proteins, lipophilins, uteroglobin, glutathione S-transferases, peroxiredoxin-6, and several uncharacterized proteins with predicted lipophilin/secretoglobin-like features.</div></div><div><h3>Conclusions</h3><div>Human and rabbit tears share a conserved core proteome while exhibiting distinct species-associated proteomic profiles. Rabbit-enriched proteins warrant further functional investigation to determine their roles in tear film stability and to evaluate their potential for future therapeutic strategies aimed at reducing excessive tear evaporation in humans.</div></div>","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":"42 ","pages":"Pages 306-316"},"PeriodicalIF":6.6,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149020255","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy and safety of 20% and 100% autologous serum eye drops in patients with severe dry eye disease: a prospective, blinded, randomized, crossover study","authors":"Dimitri Roels,&nbsp;Ineke van Gremberghe,&nbsp;Liesbeth Huys,&nbsp;Jerina Boelens,&nbsp;Joke Deprez,&nbsp;Isabelle Peene,&nbsp;Dirk Elewaut,&nbsp;Bart P. Leroy,&nbsp;Ilse Claerhout,&nbsp;Tessa Kerre","doi":"10.1016/j.jtos.2026.10.001","DOIUrl":"10.1016/j.jtos.2026.10.001","url":null,"abstract":"<div><h3>Purpose</h3><div>To evaluate the efficacy and safety of 20% and 100% autologous serum eye drops (ASED), compared to preservative-free artificial tears (PFAT), as a treatment for severe dry eye disease (DED).</div></div><div><h3>Methods</h3><div>Forty-six patients with severe DED were randomized to receive PFAT, ASED 20% and ASED 100% for 8 weeks in a crossover study design with a 2-week washout period. The Ocular Surface Disease Index (OSDI) questionnaire was used as primary outcome measure. Secondary outcomes were non-invasive tear break-up time (tBUT), best-corrected visual acuity, Schirmer 1 test, ocular surface staining (OSS) using the Sjögren's International Collaborative Clinical Alliance (SICCA) OSS score, tBUT, conjunctival injection score and Meibomian gland dysfunction grading. Additionally, serum and tear cytokine analysis and microbiological cultures were performed.</div></div><div><h3>Results</h3><div>Mean improvement in OSDI-score compared to baseline was 3.0 for PFAT (<em>p</em> = 0.35), 12.3 for ASED 20% (<em>p</em> &lt; 0.001) and 19.5 for ASED 100% (<em>p</em> &lt; 0.001). Mean improvement in SICCA OSS was 0.96 for PFAT (p = 0.002), 1.63 for ASED 20% (<em>p</em> &lt; 0.001) and 1.95 for ASED 100% (<em>p</em> &lt; 0.001). No significant differences between treatments were found for all other secondary outcomes. Cultures were positive in more than half of the PFAT and ASED vials, with the majority containing commensal flora. Analysis of tear cytokines suggested that ASED promotes a less inflammatory ocular environment than PFAT.</div></div><div><h3>Conclusions</h3><div>ASED 100% provided the greatest improvement in OSDI and SICCA OSS scores compared to baseline, supporting the clinical value of higher concentrations of autologous serum.</div></div>","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":"42 ","pages":"Pages 317-327"},"PeriodicalIF":6.6,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149088253","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transmigrated neutrophils on the ocular surface and in other tissues: A narrative review","authors":"Yutong Jin,&nbsp;Sadaf Mohsenkhani,&nbsp;Maria Walker,&nbsp;Lyndon Jones,&nbsp;Maud Gorbet","doi":"10.1016/j.jtos.2026.04.007","DOIUrl":"10.1016/j.jtos.2026.04.007","url":null,"abstract":"<div><div>Neutrophils (polymorphonuclear neutrophils, PMNs) represent 60% of the total leukocytes in the blood, playing an essential role in innate immune defence. PMNs were originally considered to be homogenous, but a growing body of evidence suggests that they exhibit considerable heterogeneity and express various phenotypes in different tissue types under physiological and pathological conditions. This review provides an overview of the PMNs phenotypes found in various human tissues, including the lungs, female reproductive tract, mouth, and eyes, under both physiological and pathological conditions. PMNs collected from the ocular surface after prolonged eye closure, termed ‘tear PMNs’, represent an emerging area of research in ocular immunology and inflammation. Their potential origin, diurnal-nocturnal pattern and functions, and their role in ocular complications are also presented and discussed.</div></div>","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":"42 ","pages":"Pages 328-340"},"PeriodicalIF":6.6,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147793739","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Combined blockade of VEGFR-3 and Itga-9 inhibits corneal lymphangiogenesis and valvulogenesis in vivo and promotes high-risk transplant survival","authors":"Gyeong Jin Kang,&nbsp;Narae Lee,&nbsp;Anna Jiang Gong,&nbsp;Guangyu Li,&nbsp;Lejun Shen,&nbsp;Yasuyuki Yokosaki,&nbsp;Lu Chen","doi":"10.1016/j.jtos.2026.06.005","DOIUrl":"10.1016/j.jtos.2026.06.005","url":null,"abstract":"<div><h3>Purpose</h3><div>Corneal transplantation is the last hope for vision restoration for corneal blindness. The rejection rate of high-risk grafts can be 50-90%, irrespective of current treatment modalities. As VEGFR-3 (vascular endothelial growth factor receptor-3) is a central regulator of lymphatic vessel formation (lymphangiogenesis, LG), integrin alpha9beta1 (Itga-9) is essential for lymphatic maturation by luminal valve formation (valvulogenesis, VG). This study is to investigate the combined blockade of VEGFR-3 and Itga-9 on high-risk corneal transplant rejection.</div></div><div><h3>Materials and methods</h3><div>High-risk corneal transplantation was performed between fully mismatched BALB/c (donor) and Prox-1-GFP (green fluorescent protein) mice in C57BL/6 background (recipient). The recipient mice were randomized to receive neutralizing antibodies of VEGFR-3 and Itga-9. Processes of corneal LG and VG were assessed <em>in vivo</em> by an advanced live imaging system. Corneal grafts were also evaluated by ophthalmic slit-lamp microscopy.</div></div><div><h3>Results</h3><div>Combined blockade of VEGFR-3 and Itga-9 significantly suppressed both LG and VG after corneal transplantation. This treatment also led to a significant promotion of graft survival in the high-risk setting.</div></div><div><h3>Conclusions</h3><div>This study offers new insights into corneal LG, VG and transplant rejection. It may also provide a novel approach to manage transplant rejection and other lymphatic- and immune-related diseases in the body.</div></div>","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":"41 ","pages":"Pages 215-219"},"PeriodicalIF":6.6,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148221306","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}

{"title":"Immunomodulatory effects and clinical application of galectins in ocular surface","authors":"Xiaorui Bao,&nbsp;Zihao Mei,&nbsp;Yuyang Fu,&nbsp;Wei Chen","doi":"10.1016/j.jtos.2026.06.006","DOIUrl":"10.1016/j.jtos.2026.06.006","url":null,"abstract":"<div><div>The ocular surface is a highly specialized biological unit essential for maintaining visual clarity and providing a robust defense against environmental insults. The interactions between cell-surface glycans and glycan-binding proteins are essential for structural and immune homeostasis. Galectins are a family of β-galactoside-binding lectins known for their diverse biological functions, notably in immune regulation. Emerging evidence highlights their critical involvement in maintaining ocular surface integrity and influencing various immunopathological conditions. This review explores the differential expression and mechanistic contributions of specific galectins, notably Gal-1, Gal-3, Gal-8, and Gal-9, in conditions such as corneal wound healing, neovascularization, dry eye disease, and various forms of ocular inflammation. Insights from clinical studies and animal models underscore their complex roles in modulating processes like epithelial barrier stability, immune cell infiltration, cytokine production, and angiogenesis. Collectively, these findings position galectins not only potential biomarkers for disease diagnosis and progression but also as therapeutic targets for interventions aimed at restoring ocular immune balance and promoting tissue repair.</div></div>","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":"41 ","pages":"Pages 163-170"},"PeriodicalIF":6.6,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148214138","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}

{"title":"Microsporidial keratitis: Global epidemiology, pathogen spectrum, and management","authors":"Sitong Shen,&nbsp;Yuan Wei,&nbsp;Bo Peng,&nbsp;Qingfeng Liang","doi":"10.1016/j.jtos.2026.06.009","DOIUrl":"10.1016/j.jtos.2026.06.009","url":null,"abstract":"<div><div>Microsporidial keratitis (MK) is an emerging ocular infection with a markedly increasing global incidence, particularly in Asia. To elucidate its global epidemiology, pathogen spectrum, and clinical management, this study systematically reviewed 76 relevant articles published between 1990 and 2025. Our analysis revealed distinct geographical clustering, with the highest disease burden reported in India, Thailand, Singapore, and China. Patient profiles exhibited a striking phenotypic divergence: superficial microsporidial keratoconjunctivitis (MKC) predominantly affected younger males and was strongly driven by environmental exposures or trauma. In contrast, the more severe microsporidial stromal keratitis (MSK) was frequently associated with older females and underlying systemic immunodeficiency. Etiologically, <em>Vittaforma corneae</em> emerged as the predominant pathogen across phenotypes. Opportunistic infections, specifically linked to severe immunosuppression, were primarily attributed to other species, such as <em>Encephalitozoon hellem</em> and <em>Encephalitozoon cuniculi</em>. Diagnostic yields from corneal scraping with staining, polymerase chain reaction, and corneal biopsy varied significantly depending on the clinical presentation. Therapeutically, MKC typically responded well to topical antimicrobials, whereas deep MSK frequently necessitated surgical intervention, primarily therapeutic penetrating keratoplasty. This systematic review consolidates the current understanding of MK, providing an evidence-based framework for its targeted prevention, risk stratification, and individualized treatment.</div></div>","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":"41 ","pages":"Pages 220-232"},"PeriodicalIF":6.6,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148229959","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}

{"title":"Intrinsic regeneration mechanisms of murine lacrimal gland epithelial cells for therapeutic applications in aqueous-deficient dry eye disease","authors":"Ingrid Zahn,&nbsp;Hannah Franke,&nbsp;Sophie Gleixner,&nbsp;Nicolas Blavet,&nbsp;Jana Dietrich,&nbsp;Philipp Arnold,&nbsp;Friedrich Paulsen","doi":"10.1016/j.jtos.2026.06.007","DOIUrl":"10.1016/j.jtos.2026.06.007","url":null,"abstract":"<div><h3>Purpose</h3><div>Aqueous-deficient dry eye disease (ADDE) results from lacrimal gland dysfunction leading to tear film instability and chronic ocular surface inflammation. Despite the gland's known regenerative potential, the intrinsic molecular mechanisms enabling epithelial recovery remain poorly understood. This study aimed to characterize intrinsic regeneration processes of murine lacrimal gland epithelial cells (mLGECs) and identify pathways with therapeutic potential.</div></div><div><h3>Methods</h3><div>Primary mLGECs were isolated from neonatal C57BL/6J mice and characterized. Acute injury was induced by brief exposure to 20% ethanol. Metabolic activity, apoptosis, and transcriptional responses were analyzed during early recovery phases. Pathway enrichment was conducted using Gene Ontology and KEGG annotations. Regeneration-associated growth factors were validated by qPCR, ELISA, and metabolic activity and wound closure assays in the presence or absence of the MAPK inhibitor SCH772984. MAPK activation was assessed by ERK1/2 phosphorylation.</div></div><div><h3>Results</h3><div>mLGECs retained expression of epithelial and lacrimal-specific markers and exhibited regulated secretory activity. RNA sequencing and ERK1/2 phosphorylation revealed activation of MAPK signaling, accompanied by strong upregulation of regenerative ligands including Hbegf, Areg, Ngf, and Gdnf. Transient protein induction of HBEGF and AREG was confirmed. Functionally, HBEGF, AREG, NGF, and GDNF markedly enhanced metabolic recovery and wound closure, whereas pharmacological MAPK inhibition markedly impaired recovery.</div></div><div><h3>Conclusion</h3><div>These results identify MAPK signaling as a major component of the intrinsic epithelial injury response in lacrimal gland cells. HBEGF and AREG emerged as prominent mediators associated with enhanced recovery. The findings provide a mechanistic basis for developing defined growth factor–based approaches to support lacrimal gland epithelial regeneration.</div></div>","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":"41 ","pages":"Pages 233-248"},"PeriodicalIF":6.6,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148255252","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dysregulated lipid metabolism in dry eye disease: Pathophysiological mechanisms and emerging treatments","authors":"Hongyu Duan,&nbsp;Peien Sheng,&nbsp;Yu Zhang,&nbsp;Baikai Ma,&nbsp;Liang Yang,&nbsp;Kyung Chul Yoon,&nbsp;Qianqian Lan,&nbsp;Hong Qi","doi":"10.1016/j.jtos.2026.06.003","DOIUrl":"10.1016/j.jtos.2026.06.003","url":null,"abstract":"<div><div>Dry eye disease (DED) is increasingly recognized as a metabolic disorder characterized by the disruption of lipid homeostasis rather than solely an inflammatory condition. This review synthesizes current evidence regarding the dysregulation of lipid metabolism in the pathogenesis of DED. Furthermore, this review systematically summarizes lipid metabolic alterations involving the meibomian glands, lacrimal glands, cornea, conjunctiva, and the tear film. The ocular surface functions as an integrated Ocular Lipid Unit (OLU) where metabolic crosstalk occurs among these tissues. Key pathological mechanisms include the impairment of mitochondrial fatty acid oxidation and the dysregulated synthesis of very-long-chain fatty acids (VLCFAs) which compromise meibum fluidity and stability. Furthermore, an imbalance between pro-inflammatory n-6 and pro-resolving n-3 polyunsaturated fatty acids (PUFAs) causes chronic ocular surface inflammation. These metabolic shifts promote lipid peroxidation and ferroptosis while systemic factors such as aging and diabetes mellitus further exacerbate ocular lipotoxicity. Advances in lipidomics reveal that physical properties like viscoelasticity and molecular ordering are more clinically relevant than absolute lipid quantity. Emerging therapeutic strategies encompass physical therapies, novel pharmacological agents targeting ferroptosis or specific metabolic enzymes, and dietary interventions. Future management should prioritize restoring metabolic homeostasis of the entire OLU and targeting specific lipid defects to achieve precision medicine in DED.</div></div>","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":"41 ","pages":"Pages 185-202"},"PeriodicalIF":6.6,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148221321","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}