Ocular SurfacePub Date : 2025-02-21DOI: 10.1016/j.jtos.2025.02.008
Antonio Ballesteros-Sánchez , Carlos Rocha-de-Lossada , José-María Sánchez-González
{"title":"Efficacy of eyelid warming devices as first-step treatment in meibomian gland dysfunction: A systematic review with meta-analysis","authors":"Antonio Ballesteros-Sánchez , Carlos Rocha-de-Lossada , José-María Sánchez-González","doi":"10.1016/j.jtos.2025.02.008","DOIUrl":"10.1016/j.jtos.2025.02.008","url":null,"abstract":"<div><h3>Purpose</h3><div>To investigate the efficacy of eyelid warming devices as first-step treatment in patients with meibomian gland dysfunction (MGD).</div></div><div><h3>Methods</h3><div>A systematic review with meta-analysis of RCTs, reporting the effects eyelid warming devices in 3 databases, PubMed, Scopus and Web of Science, was performed according to the PRISMA statement.</div></div><div><h3>Results</h3><div>Seven studies including 367 patients, and 440 eyes were analysed. The overall efficacy did not significantly favor either group when comparing eyelid warming devices to the control groups or warm towel compresses, nor between moisture chamber devices and warm compress devices. However, the change in OSDI questionnaire (SMD 0.91; 95 % CI: 0.44 to 1.39; P = 0.0002) and NIBUT (SMD 1.10; 95 % CI: 0.61 to 1.59; P < 0.0001) were significantly favorable for eyelid warming devices compared to the control groups. Similar results were obtained for tear film stability (SMD 0.97; 95 % CI: 0.32 to 1.61; P = 0.003) when comparing eyelid warming devices to warm towel compresses. Specifically, the sensitivity analysis of these groups revealed that changes in OSDI questionnaire (MD 9.41; 95 % CI: 1.70 to 17.13; <em>P</em> = 0.02; I<sup>2</sup> = 49 %) and NIBUT (MD 2.24; 95 % CI: 1.20 to 3.28; <em>P</em> < 0.0001; I<sup>2</sup> = 71 %) were significantly favorable for eyelid warming devices. When comparing moisture chamber devices and warm compress devices, only the change in TBUT (SMD 0.75; 95 % CI: 0.23 to 1.28; <em>P</em> = 0.005; I<sup>2</sup> = 30 %) were significantly favorable for moisture chamber goggles.</div></div><div><h3>Conclusions</h3><div>Despite their limited overall efficacy, eyelid warming devices significantly reduce OSDI questionnaire and improve NIBUT compared to controls or warm towel compress groups. Evidence remains insufficient to confirm whether moisture chamber devices provide better outcomes than warm compress devices. Further well-designed RCTs are needed to confirm these findings.</div></div>","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":"37 ","pages":"Pages 33-46"},"PeriodicalIF":5.9,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143477339","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 : 2025-02-13DOI: 10.1016/j.jtos.2025.02.005
Himal Kandel , Fiona Stapleton AO , Laura E. Downie , Ngozi C Chidi‐Egboka , David MIngo-Botin , Francisco Arnalich-Montiel , Saaeha Rauz , Alberto Recchioni , Sanjeeta Sitaula , Maria Markoulli , Vincent Daien , Fanny Babeau , Gerd Geerling , Jennifer P. Craig , Stephanie L. Watson OAM
{"title":"The impact of dry eye disease on patient-reported quality of life: A Save Sight Dry Eye Registry study","authors":"Himal Kandel , Fiona Stapleton AO , Laura E. Downie , Ngozi C Chidi‐Egboka , David MIngo-Botin , Francisco Arnalich-Montiel , Saaeha Rauz , Alberto Recchioni , Sanjeeta Sitaula , Maria Markoulli , Vincent Daien , Fanny Babeau , Gerd Geerling , Jennifer P. Craig , Stephanie L. Watson OAM","doi":"10.1016/j.jtos.2025.02.005","DOIUrl":"10.1016/j.jtos.2025.02.005","url":null,"abstract":"<div><h3>Purpose</h3><div>The aim of this real-world registry study was to evaluate the quality-of-life (QoL) impact of dry eye disease (DED). The specific objectives were to determine factors affecting QoL in DED, and to evaluate the psychometric properties of the Ocular Surface Disease Index (OSDI), Ocular Comfort Index (OCI), and Patient Health Questionnaire (PHQ) in a real-world DED population using modern psychometric methods.</div></div><div><h3>Methods</h3><div>This descriptive cross-sectional study included 368 DED patients (mean 54.7 ± 16.6 years; 80.2 % female) who completed one or more of the three questionnaires (OSDI, OCI and PHQ). Psychometric analysis of the QoL data was carried out with Andrich's Rating Scale Model of Rasch analysis.</div></div><div><h3>Results</h3><div>The original OSDI and OCI had disordered categories. The Rasch-optimised final QoL scales (OSDI – Overall, OSDI – Symptoms [SY], OSDI – Activity limitation [AL], OSDI – Environmental trigger [EN], OCI Overall, OCI - Frequency [FR], OCI - Intensity [IN], and PHQ) had satisfactory psychometric properties. Patients diagnosed with a mixed aqueous/evaporative DED subtype had worse mean OSDI-Overall and OSDI-AL scores than individuals with evaporative DED (p = 0.012 and 0.001 respectively). Patients with corneal neuropathic pain had worse QoL scores (OSDI-Overall, OSDI-AL, OSDI-SY, OSDI-EN, OCI-Overall, OCI-FR, OCI-IN, and PHQ; all p < 0.05) than those without. Patients who reported undergoing prior treatment or procedure for DED had worse QoL scores than those who did not (all p < 0.05 except for PHQ). The associations between DED signs (tear breakup time and staining) and symptoms were weak or not significant.</div></div><div><h3>Conclusions</h3><div>In this real-world setting, diagnoses of mixed DED, corneal neuropathic pain, and history of DED treatment/procedures were associated with worse dry eye symptoms, activity limitation, and/or QoL.</div></div>","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":"37 ","pages":"Pages 11-23"},"PeriodicalIF":5.9,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143426779","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 : 2025-02-12DOI: 10.1016/j.jtos.2025.02.007
Elyana V.T. Locatelli , Jaxon J. Huang , Jason D. Betz , Jordan J. Huang , Nicole B. Kantor , Nicholas Reyes , Elizabeth R. Felix , Wendy W. Lee , Anat Galor
{"title":"Impact of botulinum toxin type A on ocular pain with neuropathic features","authors":"Elyana V.T. Locatelli , Jaxon J. Huang , Jason D. Betz , Jordan J. Huang , Nicole B. Kantor , Nicholas Reyes , Elizabeth R. Felix , Wendy W. Lee , Anat Galor","doi":"10.1016/j.jtos.2025.02.007","DOIUrl":"10.1016/j.jtos.2025.02.007","url":null,"abstract":"<div><h3>Purpose</h3><div>To investigate the impact of botulinum toxin type A (BoNT-A) on neuropathic/nociplastic ocular pain (NOP) and identify predictors of patient outcomes.</div></div><div><h3>Methods</h3><div>A retrospective study of individuals with NOP symptoms (light sensitivity, wind/air sensitivity, persistent pain despite dry eye treatment) who received ≥1 BoNT-A injection. Primary outcome measures included if (responders vs. non-responders) and to what degree (none vs. mild vs. moderate vs. marked) individuals experienced pain improvement 4–6 weeks post-injection. Demographics and clinical exam information was compared between the groups.</div></div><div><h3>Results</h3><div>27 individuals received BoNT-A for NOP symptoms. 74 % (n = 20) reported an improvement in pain and were classified as responders. Among responders, the degree of benefit varied, with 25 % reporting mild, 45 % moderate, and 30 % marked pain improvement. Improvements in light sensitivity (37 %), wind/air sensitivity (33 %), and quality of life (QoL) (59 %) were reported by fewer individuals. 80 % of responders and 0 % of non-responders reported QoL improvements afer BoNT-A. In a multivariable model that examined predictors of response (none to marked, 0–3), the presence of fibromyalgia (FM) (β = 0.50; p = 0.004) portended a better response, while shooting pain (β = −0.47; p = 0.007) portended a worse response to BoNT-A, (full model r<sup>2</sup> = 0.53; p < 0.001). Degree of pain improvement significantly correlated with improvements in light sensitivity, wind/air sensitivity, and QoL (ρ range: 0.42–0.63; p < 0.05).</div></div><div><h3>Conclusion</h3><div>After BoNT-A, most individuals reported improved ocular pain and QoL, while fewer noted improved light and wind/air sensitivity. Some systemic and ocular factors predicted treatment response and may thus guide treatment.</div></div>","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":"37 ","pages":"Pages 24-32"},"PeriodicalIF":5.9,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143426775","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 : 2025-02-12DOI: 10.1016/j.jtos.2025.02.006
Yuli Guo , Rongrong Zhang , Minjie Zhang , Sai Luo , Wansui Li , Le Sun , Meiqin Zhong , Zuguo Liu , Yang Wu , Wei Li , Jinghua Bu
{"title":"Assessment of the clonal growth potential of meibomian gland stem/progenitor cells via clonal analysis","authors":"Yuli Guo , Rongrong Zhang , Minjie Zhang , Sai Luo , Wansui Li , Le Sun , Meiqin Zhong , Zuguo Liu , Yang Wu , Wei Li , Jinghua Bu","doi":"10.1016/j.jtos.2025.02.006","DOIUrl":"10.1016/j.jtos.2025.02.006","url":null,"abstract":"<div><h3>Purpose</h3><div>Clonal analysis is a feasible method to evaluate the status of stem/progenitor cells in epidermal or limbus investigations. This study aimed to evaluate the clonal growth potential of meibomian gland (MG) epithelial cells using clonal analysis.</div></div><div><h3>Methods</h3><div>Mouse and human MG tissues were isolated and cocultured with 3T3 feeder cells. Immunofluorescent staining of K14, K6a, and PPARγ on MG clones was applied. Holoclones, meroclones and paraclones were categorized based on clonal area. Triple staining and tile scans provided a comprehensive view of MG clone formation. MG ductal and acinar clones were cultured separately to compare stem/progenitor cell characteristics. We further evaluated an age-related MGD (ARMGD) mouse model along with two human MG samples of different ages using clonal analysis. Crystal violet staining was employed to assess clone formation efficiency (CFE).</div></div><div><h3>Results</h3><div>Both mouse and human MG epithelial cells formed clones on the feeder layers, which enlarged over time. The expression of K14, K6a, and PPARγ was decreased in differentiated clones during development. The CFE of holoclones and meroclones was approximately 1 ‰ in mouse MG clones and approximately 2.5 ‰ in holoclones and 5.6 ‰ in meroclones in human MG clones. The CFE of holoclones generated by ductal epithelial cells was significantly higher than did acinar clones. In the ARMGD mouse model and human samples, smaller clones, reduced CFE, and decreased K14+, K6a+, and PPARγ+ cells in MG clones were identified.</div></div><div><h3>Conclusions</h3><div>Clonal analysis effectively evaluates stem and progenitor cells in MGs, revealing deterioration in these cells under MGD conditions.</div></div>","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":"37 ","pages":"Pages 1-10"},"PeriodicalIF":5.9,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143426772","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 : 2025-02-06DOI: 10.1016/j.jtos.2025.02.004
Shirui Dai , Jianfeng Long , Wentao Han , Liwei Zhang , Baihua Chen
{"title":"Alleviative effect of probiotics and prebiotics on dry eye in type 2 diabetic mice through the gut-eye axis","authors":"Shirui Dai , Jianfeng Long , Wentao Han , Liwei Zhang , Baihua Chen","doi":"10.1016/j.jtos.2025.02.004","DOIUrl":"10.1016/j.jtos.2025.02.004","url":null,"abstract":"<div><div>Diabetes Mellitus (DM) is a metabolic disease that manifests as a state of “chronic low-grade inflammation”. Patients with DM have a disorder of intestinal flora. There is a discernible correlation between this disorder of intestinal flora and the onset and progression of eye diseases, which offers novel insights into treating eye diseases through the modulation of intestinal flora. Here, we demonstrated that a high-fat diet and streptozotocin injection-induced intestinal microbiota dysbiosis can lead to dry eye-like manifestations in T2DM mice. Probiotic and prebiotic treatments not only alleviated intestinal inflammation and barrier disruption, but also mitigated damage to the lacrimal barrier and suppressed immune cell infiltration and inflammatory responses. Additional mechanism investigation found that probiotics and prebiotics inhibited the TLR4/NF-κB signaling pathway and its downstream pro-inflammatory products both in the lacrimal gland and colon. 16S RNA sequencing identified a reduction in the bacterial genera <em>Akkermansia</em> and <em>Lactobacillus</em> in the fecal samples of DM mice. By contrast, treatment with probiotics and prebiotics led to a reshaping of the intestinal microbial community and a reduction in bile acid metabolites, such as taurocholic acid and deoxycholic acid. Our current study demonstrates that probiotic and prebiotic treatments can ameliorate dry eye-like symptoms and associated pathological changes in T2DM mice. Moreover, we proved that a high-fat diet and STZ-induced microbiota dysbiosis were involved in diabetic dry eye through the gut-eye axis.</div></div>","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":"36 ","pages":"Pages 244-260"},"PeriodicalIF":5.9,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143375102","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":"Effects of blinking exercises on palpebral fissure height and tear film parameters","authors":"Reiko Arita , Shima Fukuoka , Ray Matsumoto , Minako Kaido","doi":"10.1016/j.jtos.2025.02.003","DOIUrl":"10.1016/j.jtos.2025.02.003","url":null,"abstract":"<div><h3>Purpose</h3><div>Blinking is an involuntary movement essential for ocular surface health and visual comfort. While blinking exercises in patients with dry eye have been shown to improve symptoms, increase non-invasive tear film breakup time (NIBUT), and decrease incomplete blink rate (IBR), no studies have quantified improvements in eyelid opening. This study evaluated the effects of blinking exercises on palpebral fissure height (PFH), subjective symptoms, and tear film-related parameters.</div></div><div><h3>Methods</h3><div>Participants were randomly assigned to a “blinking exercise group” that performed blinking exercises after instilling artificial tear drops five times daily for three days or control group that only used artificial tear drops. Standard Patient Evaluation of Eye Dryness (SPEED) and Visual Analog Scale (VAS) scores were recorded for dryness, eye strain, ocular discomfort, blurred vision, foreign body sensation, dullness, and difficulty in opening the eyelids. The pre- and post-study measurements included lipid layer thickness, PFH, blink interval, IBR, tear meniscus height, NIBUT, fluorescein staining, and fluorescein breakup time (FBUT).</div></div><div><h3>Results</h3><div>Among 100 participants (28 males, 72 females, mean age 38.4 ± 7.4 years), 52 were in the blinking exercise group and 48 were in the control group. The blinking exercise group showed significant improvements in SPEED (<em>P</em> < 0.001), VAS scores for eye strain and discomfort (<em>P</em> = 0.003, 0.007), enlarged PFH (<em>P</em> < 0.001), prolonged NIBUT and FBUT (<em>P</em> < 0.001), and reduced IBR (<em>P</em> < 0.001) compared to the controls.</div></div><div><h3>Conclusions</h3><div>Blinking exercises improved PFH, incomplete blinking, tear film stability, and subjective symptoms in patients with dry eye.</div></div>","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":"36 ","pages":"Pages 237-243"},"PeriodicalIF":5.9,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143375103","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 : 2025-02-04DOI: 10.1016/j.jtos.2025.02.002
Filippo Bonelli , Seyedmohammad Moosavizadeh , Elisa Fasolo , Alessia Di Nella , Vanessa Barbaro , Ilaria Zorzi , Mauro Krampera , Jana D'Amato Tóthová , Diego Ponzin , Thomas Ritter , Stefano Ferrari , Umberto Rodella
{"title":"Development and optimization of an ex vivo model of corneal epithelium damage with 1-heptanol: Investigating the influence of donor clinical parameters and MSC-sEV treatment on healing capacity","authors":"Filippo Bonelli , Seyedmohammad Moosavizadeh , Elisa Fasolo , Alessia Di Nella , Vanessa Barbaro , Ilaria Zorzi , Mauro Krampera , Jana D'Amato Tóthová , Diego Ponzin , Thomas Ritter , Stefano Ferrari , Umberto Rodella","doi":"10.1016/j.jtos.2025.02.002","DOIUrl":"10.1016/j.jtos.2025.02.002","url":null,"abstract":"<div><h3>Purpose</h3><div>To develop and characterize a reproducible human corneal epithelial wound-healing model using 1-heptanol, and to investigate the healing potential of Bone Marrow-derived Mesenchymal Stromal Cell small Extracellular Vesicles (MSC-sEV) and the influence of donor characteristics on epithelial healing.</div></div><div><h3>Methods</h3><div>Eighty-eight (n = 88) human corneoscleral tissues unsuitable for transplantation were employed. Corneal epithelial damage was induced with 1-heptanol and monitored every 24 h up to 96 h using fluorescein and trypan blue staining. Histological assessment was performed on untreated and damaged tissues. Damaged areas were measured with FIJI software, and healing rates were calculated. MSC-sEV were isolated with size exclusion chromatography and characterized for their size, morphology and biomarkers. Their impact on healing was assessed in both <em>in vitro</em> scratch assays on cultured human corneal epithelial cells and on <em>ex vivo</em> 1-heptanol-damaged corneas.</div></div><div><h3>Results</h3><div>Histological analysis revealed detached corneal epithelium in the central area, while other layers remained unaffected. Healing rate peaked at 48 h post-damage. Trypan blue and Fluorescein staining correlated and the former highlighted a higher initial healing rate than the latter. Diabetic and heart-beating brain-deceased donors showed impaired healing rates. MSC-sEV (79.8 nm, spherical bilayer, positive for TSG101, CD9, CD63, and CD81) significantly improved epithelial wound healing in both <em>in vitro</em> and <em>ex vivo</em> models.</div></div><div><h3>Conclusion</h3><div>1-heptanol effectively induces reproducible corneal epithelial damage, and the <em>ex vivo</em> organ-cultured human cornea heals the epithelium within 96 h. Diabetes and donation from heart-beating brain-deceased donors reduce healing capacity. MSC-sEV boost epithelial repair in damaged corneas.</div></div>","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":"36 ","pages":"Pages 224-236"},"PeriodicalIF":5.9,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143367066","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 : 2025-02-04DOI: 10.1016/j.jtos.2025.02.001
R.Lee Kramm , Gary D. Novack
{"title":"Pipeline: US FDA efficacy requirements for treatment of ocular surface disease: Drugs vs. medical devices","authors":"R.Lee Kramm , Gary D. Novack","doi":"10.1016/j.jtos.2025.02.001","DOIUrl":"10.1016/j.jtos.2025.02.001","url":null,"abstract":"","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":"36 ","pages":"Pages 220-223"},"PeriodicalIF":5.9,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143367067","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 : 2025-01-31DOI: 10.1016/j.jtos.2025.01.013
Yong Yuan , Shingo Yasuda , Kaitlyn L. Funk , Winston Kao , Shizuya Saika , Adam Kaufman , Chia-Yang Liu
{"title":"Smad4 deficiency ameliorates the progressive corneal stroma thinning caused by the loss of Tbr1","authors":"Yong Yuan , Shingo Yasuda , Kaitlyn L. Funk , Winston Kao , Shizuya Saika , Adam Kaufman , Chia-Yang Liu","doi":"10.1016/j.jtos.2025.01.013","DOIUrl":"10.1016/j.jtos.2025.01.013","url":null,"abstract":"<div><h3>Purpose</h3><div>To understand how <em>Tbr1</em> and <em>Smad4</em> play a pivotal role in controlling ECM synthesis versus degradation for maintaining corneal stromal homeostasis and otherwise leading to corneal ectasia.</div></div><div><h3>Methods</h3><div>Keratocyte-specific and inducible knockout (iKO) of <em>Tbr1</em>, <em>Smad4</em>, or <em>Tbr1/Smad4</em> double KO (iDKO) mice were generated. OCT was used to assess corneal thickness <em>in vivo</em>. Masson's trichrome and collagen hybridizing peptide stainings were performed to examine collagen expression. Immunostaining with an anti-cathepsin B antibody was used to assess ECM degradation. Cathepsin B inhibitor, CA-074Me, eyedrop was conducted to test its effect on treating stromal thinning in <em>Tbr1</em> iKO mice.</div></div><div><h3>Results</h3><div><em>Tbr1</em> iKO and <em>Smad4</em> iKO displayed corneal thinning, but <em>Tbr1</em> iKO revealed a progressive and more severe pathology than <em>Smad4</em> iKO. <em>Tbr1</em> iKO cornea lost most of its stroma and thus a dome shape. Collagen ECM is evenly distributed in <em>Smad4</em> iKO as well as control littermates but was lost mainly in the anterior stroma of the <em>Tbr1</em> iKO. Interestingly, <em>Tbr1/Smad4</em> iDKO ameliorated <em>Tbr1</em> iKO phenotype. The basal level of Cathepsin b (Ctsb) could be detected in the control stroma but was significantly increased in the <em>Tbr1</em> iKO stromal cells and this effect was canceled in <em>Tbr1/Smad4</em> iDKO. CA-074Me eyedrops administration significantly inhibited progressive corneal thinning caused by the <em>Tbr1</em> iKO.</div></div><div><h3>Conclusion</h3><div>Our data from <em>Tbr1/Smad4</em> iDKO argued that Smad4 played a pivotal role in controlling Tbr1-dependent ECM synthesis and Tbr1-independent ECM degradation to maintain corneal stromal integrity and homeostasis.</div></div>","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":"36 ","pages":"Pages 181-189"},"PeriodicalIF":5.9,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143082811","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 : 2025-01-31DOI: 10.1016/j.jtos.2025.01.015
Fiona Stapleton , Tianni Jia , Venita DePuy , Charles Bosworth , Marc Gleeson , Jacqueline Tan
{"title":"The effect of a biweekly novel selenium sulfide-containing topical treatment in symptomatic contact lens wearers: An exploratory study","authors":"Fiona Stapleton , Tianni Jia , Venita DePuy , Charles Bosworth , Marc Gleeson , Jacqueline Tan","doi":"10.1016/j.jtos.2025.01.015","DOIUrl":"10.1016/j.jtos.2025.01.015","url":null,"abstract":"<div><h3>Purpose</h3><div>To explore effects of topical 1 % selenium sulfide on signs and symptoms in symptomatic contact lens-wearers, in an exploratory 4-month prospective placebo-controlled double-masked randomised trial.</div></div><div><h3>Methods</h3><div>Symptomatic wearers (Contact Lens Dry Eye Questionnaire-8 [CLDEQ-8] score>12) with meibomian gland dysfunction (meibomian gland score (MGS)≤12), were enrolled and received either active (AZR-MD-001-containing 1 % selenium sulfide), or vehicle ointment, to the lower eyelid margin twice-weekly. MGS, meibomian glands-yielding liquid secretion (MGYLS), lipid layer thickness, tear meniscus height, tear break-up time, tear evaporation rate, lid wiper epitheliopathy, CLDEQ-8 and comfortable wear time (CWT) were measured at baseline and to 4-months. Differences between active and placebo were compared to baseline.</div></div><div><h3>Results</h3><div>Fourteen participants (5M:9 F, 30.8 ± 13.8 years) completed the study. In the active group, change in MGS from baseline improved by 1-month (mean difference 7.9 ± 8.0, p = 0.03), to 4-months (16.0 ± 11.3, p < 0.01). MGYLS improved from baseline by 1.5-months (4.0 ± 3.3) to 4-months (4.1 ± 4.3, p < 0.01). In the vehicle, change in MGS (12.1 ± 10.7) and MGYLS (3.9 ± 3.2) were improved at 4-months only (p < 0.01). CLDEQ-8 score improved at 1-month and 4-months compared to baseline (−4.4 ± 3.2, −5.1 ± 4.7, p ≤ 0.02) in the active and at 4-months only in the vehicle group (−4.4 ± 6.4, p = 0.02). In the active group, CLDEQ-8 visual function scores improved at 1- and 4-months (p ≤ 0.02) and CWT at 4-months (median 7 vs.10 h, p = 0.025). Other signs were unchanged.</div></div><div><h3>Conclusions</h3><div>This exploratory study indicates that twice-weekly use of AZR-MD-001 ointment can rapidly improve gland patency and secretion in symptomatic contact lens-wearers. AZR-MD-001 reduced changeable/blurry vision and prolonged CWT, suggesting relevant future endpoints.</div></div>","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":"36 ","pages":"Pages 190-197"},"PeriodicalIF":5.9,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143082778","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}