Ocular SurfacePub Date : 2024-05-03DOI: 10.1016/j.jtos.2024.04.006
Jingliang He , Fang Zheng , Li Zhang , Jiangxiong Cai , Yoko Ogawa , Kazuo Tsubota , Shan Liu , Xiuming Jin
{"title":"Single-cell RNA-sequencing reveals the transcriptional landscape of lacrimal gland in GVHD mouse model","authors":"Jingliang He , Fang Zheng , Li Zhang , Jiangxiong Cai , Yoko Ogawa , Kazuo Tsubota , Shan Liu , Xiuming Jin","doi":"10.1016/j.jtos.2024.04.006","DOIUrl":"https://doi.org/10.1016/j.jtos.2024.04.006","url":null,"abstract":"<div><h3>Purpose</h3><p>To investigate the global transcriptional landscape of lacrimal gland cell populations in the GVHD mouse model.</p></div><div><h3>Methods</h3><p>Single-cell RNA sequencing and further bioinformatic analysis of dissociated lacrimal gland (LG) cells from the mouse model were performed. Parts of transcriptional results were confirmed by immunofluorescence staining.</p></div><div><h3>Results</h3><p>We identified 23 cell populations belonging to 11 cell types. In GVHD LG, the proportion of acinar cells, myoepithelial cells, and endothelial cells was remarkably decreased, while T cells and macrophages were significantly expanded. Gene expression analysis indicated decreased secretion function, extracellular matrix (ECM) synthesis, and increased chemokines of myoepithelial cells. A newly described epithelial population named <em>Lrg1</em><sup>high</sup> epithelial cells, expressing distinct gene signatures, was exclusively identified in GVHD LG. The fibroblasts exhibited an inflammation gene pattern. The gene pattern of endothelial cells suggested an increased ability to recruit immune cells and damaged cell-cell junctions. T cells were mainly comprised of Th2 cells and effective memory CD8<sup>+</sup> T cells. GVHD macrophages exhibited a Th2 cell-linked pattern.</p></div><div><h3>Conclusions</h3><p>This single-cell atlas uncovered alterations of proportion and gene expression patterns of cell populations and constructed cell-cell communication networks of GVHD LG. These data may provide some new insight into understanding the development of ocular GVHD.</p></div>","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":"33 ","pages":"Pages 50-63"},"PeriodicalIF":6.4,"publicationDate":"2024-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140843477","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 : 2024-04-28DOI: 10.1016/j.jtos.2024.04.004
Rajni Rajan, Eve Makrai, Ji-hyun Lee, Sumeer Singh, Holly R. Chinnery, Laura E. Downie
{"title":"Evaluating the efficacy and safety of therapeutic interventions for corneal neuropathy: A systematic review","authors":"Rajni Rajan, Eve Makrai, Ji-hyun Lee, Sumeer Singh, Holly R. Chinnery, Laura E. Downie","doi":"10.1016/j.jtos.2024.04.004","DOIUrl":"10.1016/j.jtos.2024.04.004","url":null,"abstract":"<div><p>Corneal neuropathy involves corneal nerve damage that disrupts ocular surface integrity, negatively impacting quality-of-life from pain and impaired vision. Any ocular or systemic condition that damages the trigeminal nerve can lead to corneal neuropathy. However, the condition currently does not have standardized diagnostic criteria or treatment protocols. The primary aim of this systematic review was to evaluate the efficacy and safety of interventions for treating corneal neuropathy. Randomized controlled trials (RCTs) that investigated corneal neuropathy treatments were eligible if the intervention(s) was compared to a placebo or active comparator. Comprehensive searches were conducted in Ovid MEDLINE, Ovid Embase and clinical trial registries from inception to July 2022. The Cochrane Risk-of-Bias 2 tool was used to assess study methodological quality. Certainty of the body of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Overall, 20 RCTs were included. Evaluated interventions comprised regenerative therapies (n = 6 studies), dietary supplements (n = 4), anti-glycemic agents (n = 3), combination therapy (n = 3), supportive therapies (n = 2) and systemic pain pharmacotherapies (n = 2). Nine RCTs were judged at high risk of bias for most outcomes. Definitions for corneal neuropathy in the populations varied substantially across studies, consistent with lack of consensus on diagnostic criteria. A diverse range of outcomes were quantified, likely reflecting absence of an agreed core outcome set. There was insufficient evidence to draw definitive conclusions on the efficacy or safety of any intervention. There was low or very low certainty evidence for several neuroregenerative agents and dietary supplements for improving corneal nerve fiber length in corneal neuropathy due to dry eye disease and diabetes. Low or very low certainty evidence was found for neuroregenerative therapies and dietary supplements not altering corneal immune cell density. This review identifies a need to standardize the clinical definition of corneal neuropathy and define a minimum set of core outcome measures. Together, this will provide a foundation for improved phenotyping of clinical populations in studies, and improve the capacity to synthesize data to inform evidence-based care.</p><p>Protocol registration: PROSPERO ID: CRD42022348475.</p></div>","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":"33 ","pages":"Pages 80-98"},"PeriodicalIF":6.4,"publicationDate":"2024-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1542012424000508/pdfft?md5=8a076572bce5de190f42a40a1f2c3b2d&pid=1-s2.0-S1542012424000508-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140871826","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}
Ocular SurfacePub Date : 2024-04-26DOI: 10.1016/j.jtos.2024.04.005
Xuming Zhu , Mingang Xu , Sarah E. Millar
{"title":"HDAC1/2 and HDAC3 play distinct roles in controlling adult Meibomian gland homeostasis","authors":"Xuming Zhu , Mingang Xu , Sarah E. Millar","doi":"10.1016/j.jtos.2024.04.005","DOIUrl":"https://doi.org/10.1016/j.jtos.2024.04.005","url":null,"abstract":"<div><h3>Purpose</h3><p>To investigate the roles of HDAC1/2 and HDAC3 in adult Meibomian gland (MG) homeostasis.</p></div><div><h3>Methods</h3><p>HDAC1/2 or HDAC3 were inducibly deleted in MG epithelial cells of adult mice. The morphology of MG was examined. Proliferation, apoptosis, and expression of MG acinus and duct marker genes, meibocyte differentiation genes, and HDAC target genes, were analyzed via immunofluorescence, TUNEL assay, and RNA in situ hybridization.</p></div><div><h3>Results</h3><p>Co-deletion of HDAC1/2 in MG epithelium caused gradual loss of acini and formation of cyst-like structures in the central duct. These phenotypes required homozygous deletion of both HDAC1 and HDAC2, indicating that they function redundantly in the adult MG. Short-term deletion of HDAC1/2 in MG epithelium had little effect on meibocyte maturation but caused decreased proliferation of acinar basal cells, excessive DNA damage, ectopic apoptosis, and increased p53 acetylation and <em>p16</em> expression in the MG. By contrast, HDAC3 deletion in MG epithelium caused dilation of central duct, atrophy of acini, defective meibocyte maturation, increased acinar basal cell proliferation, and ectopic apoptosis and DNA damage. Levels of p53 acetylation and p21 expression were elevated in HDAC3-deficient MGs, while the expression of the differentiation regulator PPARγ and the differentiation markers PLIN2 and FASN was downregulated.</p></div><div><h3>Conclusions</h3><p>HDAC1 and HDAC2 function redundantly in adult Meibomian gland epithelial progenitor cells and are essential for their proliferation and survival, but not for acinar differentiation, while HDAC3 is required to limit acinar progenitor cell proliferation and permit differentiation. HDAC1/2 and HDAC3 have partially overlapping roles in maintaining survival of MG cells.</p></div>","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":"33 ","pages":"Pages 39-49"},"PeriodicalIF":6.4,"publicationDate":"2024-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140816130","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 : 2024-04-01DOI: 10.1016/j.jtos.2024.02.001
Lyvia J. Zhang, Reza Dana, Alice C. Lorch, Tobias Elze, Joan W. Miller, Thomas H. Dohlman, Isdin Oke, IRIS®Registry Analytic Center Consortium
{"title":"Visual outcomes of children undergoing penetrating keratoplasty in the US","authors":"Lyvia J. Zhang, Reza Dana, Alice C. Lorch, Tobias Elze, Joan W. Miller, Thomas H. Dohlman, Isdin Oke, IRIS®Registry Analytic Center Consortium","doi":"10.1016/j.jtos.2024.02.001","DOIUrl":"10.1016/j.jtos.2024.02.001","url":null,"abstract":"","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":"32 ","pages":"Pages 219-221"},"PeriodicalIF":6.4,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139975276","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 : 2024-04-01DOI: 10.1016/j.jtos.2024.03.004
Agni Malmin , Vilde M. Thomseth , Per T. Førland , Hans C.D. Aass , Sjur Reppe , Markus V.T. Olsen , Birger Lindtjørn , Xiangjun Chen , Inga B.K. Haugen , Tor P. Utheim , Vegard A. Forsaa
{"title":"Tear cytokine levels are reduced in patients treated with intravitreal injections","authors":"Agni Malmin , Vilde M. Thomseth , Per T. Førland , Hans C.D. Aass , Sjur Reppe , Markus V.T. Olsen , Birger Lindtjørn , Xiangjun Chen , Inga B.K. Haugen , Tor P. Utheim , Vegard A. Forsaa","doi":"10.1016/j.jtos.2024.03.004","DOIUrl":"10.1016/j.jtos.2024.03.004","url":null,"abstract":"<div><h3>Purpose</h3><p>To investigate cytokine levels in the tear fluid of patients receiving serial intravitreal injections (IVI) with anti-vascular endothelial growth factor (anti-VEGF) for neovascular age-related macular degeneration (nAMD).</p></div><div><h3>Methods</h3><p>Concentrations of six cytokines (IFN-γ, IL-1β, IL-6, IL-8, TNF and VEGF) in tears of patients receiving anti-VEGF in one eye were assayed using multiplex cytometric bead array. The fellow untreated eye served as control. Tear sampling was performed on a single occasion at a minimum of four weeks after IVI. Patients underwent a pre-IVI antisepsis protocol with povidone-iodine.</p></div><div><h3>Results</h3><p>Tear fluid from thirty patients with a mean age of 78.8 years (range 58–90) was assayed. Subjects received a median of 43.5 (range 22–106) IVI in one eye. The median level of IFN-γ was 0.33 (interquartile range (IQR) 0.22–0.52) pg/mg of total protein in injected eyes versus 0.41 (IQR 0.21–1.05) pg/mg in fellow eyes (p = 0.017). For TNF, a median level of 0.12 (IQR 0.08–0.18) pg/mg of total protein was found in injected eyes versus 0.14 (IQR 0.07–0.33) pg/mg of total protein in fellow eyes (p = 0.019). There were no differences between injected and fellow eyes regarding the levels of IL-1β, IL-6, IL-8 and VEGF.</p></div><div><h3>Conclusion</h3><p>Tear fluid in eyes receiving serial IVI with anti-VEGF and preoperative povidone-iodine antisepsis constitutes lower levels of the pro-inflammatory cytokines IFN-γ and TNF compared to fellow eyes. This provides biochemical support of previous findings of reduced signs of inflammation and healthier tear film parameters in patients treated with serial IVI.</p></div>","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":"32 ","pages":"Pages 222-226"},"PeriodicalIF":6.4,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1542012424000338/pdfft?md5=857e29fe9929675700b9abc846e9931f&pid=1-s2.0-S1542012424000338-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140137646","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}
Ocular SurfacePub Date : 2024-03-30DOI: 10.1016/j.jtos.2024.03.011
August Beisel , Garrett Jones , Joshua Glass , Tae Jin Lee , Marc Töteberg-Harms , Amy Estes , Lane Ulrich , Kathryn Bollinger , Shruti Sharma , Ashok Sharma
{"title":"Comparative analysis of human tear fluid and aqueous humor proteomes","authors":"August Beisel , Garrett Jones , Joshua Glass , Tae Jin Lee , Marc Töteberg-Harms , Amy Estes , Lane Ulrich , Kathryn Bollinger , Shruti Sharma , Ashok Sharma","doi":"10.1016/j.jtos.2024.03.011","DOIUrl":"10.1016/j.jtos.2024.03.011","url":null,"abstract":"<div><h3>Purpose</h3><p>Technological advancements allowing for the analysis of low-volume samples have led to the investigation of human tear fluid and aqueous humor (AH) as potential biomarker sources. However, acquiring AH samples poses significant challenges, making human tear fluid a more accessible alternative. This study aims to compare the protein compositions of these two biofluids to evaluate their suitability for biomarker discovery.</p></div><div><h3>Methods</h3><p>Paired tear and AH samples were collected from 20 patients undergoing cataract surgery. Tear samples were collected using Schirmer strips prior to surgery, and AH samples were collected from the anterior chamber immediately after corneal incision. Proteins were extracted and analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS).</p></div><div><h3>Results</h3><p>A total of 481 proteins were identified in greater than 50% of the tear samples, and 191 proteins were detected in greater than 50% of the AH samples. Of these proteins, 82 were found to be common between the two biofluids, with ALB, LTF, TF, LCN1, and IGKC being the most abundant.</p></div><div><h3>Conclusion</h3><p>Although tear fluid and the AH are functionally independent and physically separated, many of the proteins detected in AH were also detected in tears. This direct comparison of the proteomic content of tear fluid and AH may aid in further investigation of tear fluid as a source of readily accessible biomarkers for various human diseases.</p></div>","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":"33 ","pages":"Pages 16-22"},"PeriodicalIF":6.4,"publicationDate":"2024-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140338423","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 : 2024-03-28DOI: 10.1016/j.jtos.2024.03.010
Michael T.M. Wang , Jay J. Meyer , Ally L. Xue , Barry Power , Jennifer P. Craig
{"title":"Predictive performance of corneal and lid margin sensitivity for dry eye disease: An investigator-masked, prospective, prognostic accuracy study","authors":"Michael T.M. Wang , Jay J. Meyer , Ally L. Xue , Barry Power , Jennifer P. Craig","doi":"10.1016/j.jtos.2024.03.010","DOIUrl":"10.1016/j.jtos.2024.03.010","url":null,"abstract":"<div><h3>Purpose</h3><p>To evaluate the prognostic ability of non-contact esthesiometry corneal and lid margin sensitivity measurements in detecting symptoms and signs of dry eye disease, as defined by the global consensus TFOS DEWS II criteria.</p></div><div><h3>Methods</h3><p>A total of 87 community residents (58 females; mean ± SD age, 53 ± 16 years) were recruited in an investigator-masked, prospective, prognostic accuracy study. Dry eye symptomology, tear film parameters, and ocular surface characteristics were evaluated in a single clinical session, and non-contact esthesiometry corneal and lid margin sensitivity measurements performed by an independent masked assessor.</p></div><div><h3>Results</h3><p>Overall, 49 (56%) participants fulfilled the TFOS DEWS II criteria for dry eye disease, while 57 (66%) exhibited clinical symptoms, and 67 (77%) had positive signs. The prognostic abilities of corneal and lid margin sensitivity measurements were significantly greater than chance for the detection dry eye signs (both p ≤ 0.03), but not for symptoms or overall disease diagnosis (all p > 0.10). The Youden-optimal prognostic cut-offs for corneal and lid margin sensitivity thresholds were both ≥0.8 mbar for the detection of clinical dry eye signs. Lid margin sensitivity demonstrated marginally higher predictive performance than corneal sensitivity (C-statistic, 0.688 versus 0.658), and was significantly correlated with tear film stability, corneal, conjunctival and lid wiper staining (all p < 0.05).</p></div><div><h3>Conclusions</h3><p>Corneal and lid margin sensitivity demonstrated moderate prognostic utility for detecting clinical dry eye signs. Future research is warranted to investigate the utility of incorporating non-contact esthesiometry in the workup for dry eye disease and neurotrophic keratopathy.</p></div>","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":"33 ","pages":"Pages 11-15"},"PeriodicalIF":6.4,"publicationDate":"2024-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1542012424000399/pdfft?md5=ce0dce8ce6a262c8e730cd050187ca48&pid=1-s2.0-S1542012424000399-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140330477","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}