Ocular Surface最新文献

Assessment of the clonal growth potential of meibomian gland stem/progenitor cells via clonal analysis

IF 5.9 1区医学 Q1 OPHTHALMOLOGY

Ocular Surface

Pub Date : 2025-02-12 DOI: 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

Purpose

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.

Methods

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).

Results

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.

Conclusions

Clonal analysis effectively evaluates stem and progenitor cells in MGs, revealing deterioration in these cells under MGD conditions.

{"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}

引用次数: 0

Effects of blinking exercises on palpebral fissure height and tear film parameters

IF 5.9 1区医学 Q1 OPHTHALMOLOGY

Ocular Surface

Pub Date : 2025-02-05 DOI: 10.1016/j.jtos.2025.02.003

Reiko Arita , Shima Fukuoka , Ray Matsumoto , Minako Kaido

Purpose

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.

Methods

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).

Results

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 (P < 0.001), VAS scores for eye strain and discomfort (P = 0.003, 0.007), enlarged PFH (P < 0.001), prolonged NIBUT and FBUT (P < 0.001), and reduced IBR (P < 0.001) compared to the controls.

Conclusions

Blinking exercises improved PFH, incomplete blinking, tear film stability, and subjective symptoms in patients with dry eye.

{"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}

引用次数: 0

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

IF 5.9 1区医学 Q1 OPHTHALMOLOGY

Ocular Surface

Pub Date : 2025-02-04 DOI: 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

Purpose

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.

Methods

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 in vitro scratch assays on cultured human corneal epithelial cells and on ex vivo 1-heptanol-damaged corneas.

Results

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 in vitro and ex vivo models.

Conclusion

1-heptanol effectively induces reproducible corneal epithelial damage, and the ex vivo 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.

{"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}

引用次数: 0

Pipeline: US FDA efficacy requirements for treatment of ocular surface disease: Drugs vs. medical devices

IF 5.9 1区医学 Q1 OPHTHALMOLOGY

Ocular Surface

Pub Date : 2025-02-04 DOI: 10.1016/j.jtos.2025.02.001

R.Lee Kramm , Gary D. Novack

引用次数: 0

Smad4 deficiency ameliorates the progressive corneal stroma thinning caused by the loss of Tbr1

IF 5.9 1区医学 Q1 OPHTHALMOLOGY

Ocular Surface

Pub Date : 2025-01-31 DOI: 10.1016/j.jtos.2025.01.013

Yong Yuan , Shingo Yasuda , Kaitlyn L. Funk , Winston Kao , Shizuya Saika , Adam Kaufman , Chia-Yang Liu

Purpose

To understand how Tbr1 and Smad4 play a pivotal role in controlling ECM synthesis versus degradation for maintaining corneal stromal homeostasis and otherwise leading to corneal ectasia.

Methods

Keratocyte-specific and inducible knockout (iKO) of Tbr1, Smad4, or Tbr1/Smad4 double KO (iDKO) mice were generated. OCT was used to assess corneal thickness in vivo. 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 Tbr1 iKO mice.

Results

Tbr1 iKO and Smad4 iKO displayed corneal thinning, but Tbr1 iKO revealed a progressive and more severe pathology than Smad4 iKO. Tbr1 iKO cornea lost most of its stroma and thus a dome shape. Collagen ECM is evenly distributed in Smad4 iKO as well as control littermates but was lost mainly in the anterior stroma of the Tbr1 iKO. Interestingly, Tbr1/Smad4 iDKO ameliorated Tbr1 iKO phenotype. The basal level of Cathepsin b (Ctsb) could be detected in the control stroma but was significantly increased in the Tbr1 iKO stromal cells and this effect was canceled in Tbr1/Smad4 iDKO. CA-074Me eyedrops administration significantly inhibited progressive corneal thinning caused by the Tbr1 iKO.

Conclusion

Our data from Tbr1/Smad4 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.

{"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}

引用次数: 0

The effect of a biweekly novel selenium sulfide-containing topical treatment in symptomatic contact lens wearers: An exploratory study

IF 5.9 1区医学 Q1 OPHTHALMOLOGY

Ocular Surface

Pub Date : 2025-01-31 DOI: 10.1016/j.jtos.2025.01.015

Fiona Stapleton , Tianni Jia , Venita DePuy , Charles Bosworth , Marc Gleeson , Jacqueline Tan

Purpose

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.

Methods

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.

Results

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.

Conclusions

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.

{"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}

引用次数: 0

Effect of hematopoietic stem cell transplantation on meibomian gland structure

IF 5.9 1区医学 Q1 OPHTHALMOLOGY

Ocular Surface

Pub Date : 2025-01-31 DOI: 10.1016/j.jtos.2025.01.014

Andrea Novo-Diez , Jens Horstmann , Itziar Fernández , Margarita Calonge , María J. González-García , Philipp Steven

Purpose

To assess morphological changes in the meibomian glands (MGs) pre- and post-hematopoietic stem cell transplantation (HSCT).

Methods

Participants yet to undergo HSCT were included in a pre-HSCT group. Meibography images of both lids were graded using Pult's meiboscale and analyzed using a semi-automatic software program. Meibography variables in the pre-HSCT group were compared with those in a control group of healthy participants. The follow-up group, a subset of the pre-HSCT group, comprised participants followed up for at least 6 months post-HSCT. Ocular Surface Disease Index (OSDI), tear break-up time, corneal fluorescein staining, and Schirmer test were performed. The differences in meibography variables and ocular surface tests pre- and post-HSCT were analyzed.

Results

Pre-HSCT and control groups comprised 181 and 24 participants, respectively. The pre-HSCT group had a higher meiboscale in the lower lid (2 vs. 1, p = 0.011) than controls. The follow-up group comprised 20 patients followed up for 12.75 months post-HSCT. After HSCT, the meiboscale of the upper lid was higher (2 vs. 1, p = 0.011), the MG area was lower in both lids (upper lid = 16.14 % vs. 21.49 %, p = 0.001; lower lid = 11.92 % vs. 17.59 %, p = 0.011), and the OSDI increased (15.2 vs. 26.85, p = 0.018) in the second visit compared to the first visit.

Conclusions

Alterations in meibography were observed in patients pre- and post-HSCT. This may be attributed to the effect of treatments administered pre-HSCT, although an additive effect of conditioning regimen in the long-term cannot be discarded.

{"title":"Effect of hematopoietic stem cell transplantation on meibomian gland structure","authors":"Andrea Novo-Diez , Jens Horstmann , Itziar Fernández , Margarita Calonge , María J. González-García , Philipp Steven","doi":"10.1016/j.jtos.2025.01.014","DOIUrl":"10.1016/j.jtos.2025.01.014","url":null,"abstract":"<div><h3>Purpose</h3><div>To assess morphological changes in the meibomian glands (MGs) pre- and post-hematopoietic stem cell transplantation (HSCT).</div></div><div><h3>Methods</h3><div>Participants yet to undergo HSCT were included in a pre-HSCT group. Meibography images of both lids were graded using Pult's meiboscale and analyzed using a semi-automatic software program. Meibography variables in the pre-HSCT group were compared with those in a control group of healthy participants. The follow-up group, a subset of the pre-HSCT group, comprised participants followed up for at least 6 months post-HSCT. Ocular Surface Disease Index (OSDI), tear break-up time, corneal fluorescein staining, and Schirmer test were performed. The differences in meibography variables and ocular surface tests pre- and post-HSCT were analyzed.</div></div><div><h3>Results</h3><div>Pre-HSCT and control groups comprised 181 and 24 participants, respectively. The pre-HSCT group had a higher meiboscale in the lower lid (2 vs. 1, p = 0.011) than controls. The follow-up group comprised 20 patients followed up for 12.75 months post-HSCT. After HSCT, the meiboscale of the upper lid was higher (2 vs. 1, p = 0.011), the MG area was lower in both lids (upper lid = 16.14 % vs. 21.49 %, p = 0.001; lower lid = 11.92 % vs. 17.59 %, p = 0.011), and the OSDI increased (15.2 vs. 26.85, p = 0.018) in the second visit compared to the first visit.</div></div><div><h3>Conclusions</h3><div>Alterations in meibography were observed in patients pre- and post-HSCT. This may be attributed to the effect of treatments administered pre-HSCT, although an additive effect of conditioning regimen in the long-term cannot be discarded.</div></div>","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":"36 ","pages":"Pages 173-180"},"PeriodicalIF":5.9,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143082809","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}

引用次数: 0

A large hypothesis-free proteomics study investigating serum inflammatory markers as biomarkers of dry eye disease

IF 5.9 1区医学 Q1 OPHTHALMOLOGY

Ocular Surface

Pub Date : 2025-01-28 DOI: 10.1016/j.jtos.2025.01.011

Jelle Vehof , Amber Rhee , Niccolò Rossi , Mario Falchi , Christopher J. Hammond , Frances M.K. Williams

Purpose

To test the association between serum inflammatory markers and dry eye disease (DED) using a hypothesis-free proteomic approach in a population-based cohort.

Methods

A total of 2602 unselected community-based participants (mean age 61.5 (range 21–92 years), 94.4 % female) from the TwinsUK cohort were examined. DED was assessed with the validated Women’s Health Study (WHS) questionnaire; cases were defined by either a previous clinician diagnosis or presence of highly symptomatic dry eye. Serum inflammatory markers were assessed with the Olink Target 96 Inflammation panel. We performed logistic regression mixed effect models, adjusted for age, BMI, sex, and twin relatedness, with false discovery rate (FDR) correction.

Results

Prevalence of WHS-defined DED was 29.1 %, with 26.2 % having a previous diagnosis of DED and 16.5 % having highly symptomatic dry eye. Of 74 inflammatory markers, significant associations with WHS-defined DED were found for neurotrophin-3 (NT-3; OR: 0.68, FDR p-value: 0.043), natural killer-cell receptor 2B4 (CD244; OR: 0.68, FDR p-value: 0.043), C-X-C motif chemokines (CXCL) 9 (OR: 1.23, FDR p-value: 0.043) and CXCL10 (OR: 1.22, FDR p-value: 0.043). Significant association with highly symptomatic dry eye were found with increased levels of CCL19, CXCL9, CXCL10, CCL20, CX3CL1 (fractalkine), TNF, CDCP1, and CCL25.

Conclusions

This large population-based study found several serum inflammatory proteins to be associated with DED, confirming and adding to previous targeted tear and corneal and conjunctival expression studies in murine models and clinic-based case-control studies. Of interest, a novel potential biomarker NT-3, which plays a role in corneal nerve function, was identified.

{"title":"A large hypothesis-free proteomics study investigating serum inflammatory markers as biomarkers of dry eye disease","authors":"Jelle Vehof , Amber Rhee , Niccolò Rossi , Mario Falchi , Christopher J. Hammond , Frances M.K. Williams","doi":"10.1016/j.jtos.2025.01.011","DOIUrl":"10.1016/j.jtos.2025.01.011","url":null,"abstract":"<div><h3>Purpose</h3><div>To test the association between serum inflammatory markers and dry eye disease (DED) using a hypothesis-free proteomic approach in a population-based cohort.</div></div><div><h3>Methods</h3><div>A total of 2602 unselected community-based participants (mean age 61.5 (range 21–92 years), 94.4 % female) from the TwinsUK cohort were examined. DED was assessed with the validated Women’s Health Study (WHS) questionnaire; cases were defined by either a previous clinician diagnosis or presence of highly symptomatic dry eye. Serum inflammatory markers were assessed with the Olink Target 96 Inflammation panel. We performed logistic regression mixed effect models, adjusted for age, BMI, sex, and twin relatedness, with false discovery rate (FDR) correction.</div></div><div><h3>Results</h3><div>Prevalence of WHS-defined DED was 29.1 %, with 26.2 % having a previous diagnosis of DED and 16.5 % having highly symptomatic dry eye. Of 74 inflammatory markers, significant associations with WHS-defined DED were found for neurotrophin-3 (NT-3; OR: 0.68, FDR p-value: 0.043), natural killer-cell receptor 2B4 (CD244; OR: 0.68, FDR p-value: 0.043), C-X-C motif chemokines (CXCL) 9 (OR: 1.23, FDR p-value: 0.043) and CXCL10 (OR: 1.22, FDR p-value: 0.043). Significant association with highly symptomatic dry eye were found with increased levels of CCL19, CXCL9, CXCL10, CCL20, CX3CL1 (fractalkine), TNF, CDCP1, and CCL25.</div></div><div><h3>Conclusions</h3><div>This large population-based study found several serum inflammatory proteins to be associated with DED, confirming and adding to previous targeted tear and corneal and conjunctival expression studies in murine models and clinic-based case-control studies. Of interest, a novel potential biomarker NT-3, which plays a role in corneal nerve function, was identified.</div></div>","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":"36 ","pages":"Pages 198-208"},"PeriodicalIF":5.9,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143070413","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}

引用次数: 0

Application of stem cell-derived exosomes in anterior segment eye diseases: A comprehensive update review

IF 5.9 1区医学 Q1 OPHTHALMOLOGY

Ocular Surface

Pub Date : 2025-01-28 DOI: 10.1016/j.jtos.2025.01.012

Masoud Khorrami-Nejad , Hesam Hashemian , Ali Majdi , Khosrow Jadidi , Hossein Aghamollaei , Ali Hadi

Mesenchymal stem cell (MSC) therapy has emerged as a promising approach for addressing various eye-related conditions. Yet, its clinical application faces challenges due to issues such as limited biocompatibility and difficulties in effectively delivering treatment to specific ocular tissues. Recent studies have shifted attention towards MSC-derived exosomes, which share similar regenerative, reparative, and immunomodulatory capabilities with their origin cells. This review delves into the latest research on the use of MSC-derived exosomes for treating anterior segment diseases of the eye. It explores the exosomes' composition, biological functions, and the methods used for their isolation, as well as their roles in disease progression, diagnosis, and therapy. The review critically assesses the therapeutic advantages and mechanisms of action of MSC-derived exosomes in treating conditions like dry eye disease, Sjogren's syndrome, keratoconus, corneal lesions, and corneal allograft rejection. Additionally, it discusses the obstacles and future prospects of employing MSC-derived exosomes as innovative therapies for anterior segment eye diseases. This comprehensive overview underscores the significant potential of MSC-derived exosomes in transforming the treatment paradigm for anterior segment eye disorders, while also highlighting the necessity for further research to enhance their clinical application.

{"title":"Application of stem cell-derived exosomes in anterior segment eye diseases: A comprehensive update review","authors":"Masoud Khorrami-Nejad , Hesam Hashemian , Ali Majdi , Khosrow Jadidi , Hossein Aghamollaei , Ali Hadi","doi":"10.1016/j.jtos.2025.01.012","DOIUrl":"10.1016/j.jtos.2025.01.012","url":null,"abstract":"<div><div>Mesenchymal stem cell (MSC) therapy has emerged as a promising approach for addressing various eye-related conditions. Yet, its clinical application faces challenges due to issues such as limited biocompatibility and difficulties in effectively delivering treatment to specific ocular tissues. Recent studies have shifted attention towards MSC-derived exosomes, which share similar regenerative, reparative, and immunomodulatory capabilities with their origin cells. This review delves into the latest research on the use of MSC-derived exosomes for treating anterior segment diseases of the eye. It explores the exosomes' composition, biological functions, and the methods used for their isolation, as well as their roles in disease progression, diagnosis, and therapy. The review critically assesses the therapeutic advantages and mechanisms of action of MSC-derived exosomes in treating conditions like dry eye disease, Sjogren's syndrome, keratoconus, corneal lesions, and corneal allograft rejection. Additionally, it discusses the obstacles and future prospects of employing MSC-derived exosomes as innovative therapies for anterior segment eye diseases. This comprehensive overview underscores the significant potential of MSC-derived exosomes in transforming the treatment paradigm for anterior segment eye disorders, while also highlighting the necessity for further research to enhance their clinical application.</div></div>","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":"36 ","pages":"Pages 209-219"},"PeriodicalIF":5.9,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143070467","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}

引用次数: 0

Label-free quantitative imaging of conjunctival goblet cells

IF 5.9 1区医学 Q1 OPHTHALMOLOGY

Ocular Surface

Pub Date : 2025-01-23 DOI: 10.1016/j.jtos.2025.01.009

Noseong Park , Suil Jeon , Seonghan Kim , Jungbin Lee , Jin Suk Ryu , Wan Jae Choi , Chang Ho Yoon , Chulmin Joo , Ki Hean Kim

Purpose

To introduce and validate quantitative oblique back-illumination microscopy (qOBM) as a label-free, high-contrast imaging technique for visualizing conjunctival goblet cells (GCs) and assessing their functional changes.

Methods

qOBM was developed in conjunction with moxifloxacin-based fluorescence microscopy (MBFM), which was used for validating GC imaging. Initial validation was conducted with polystyrene beads, followed by testing on normal mouse conjunctiva under both ex-vivo and in-vivo conditions. Longitudinal qOBM imaging was performed on ex-vivo mouse conjunctiva exposed to hyperosmotic stress (induced by 1000 mOsm/kg NaCl solution) and normal saline (300 mOsm/kg balanced salt solution, BSS). Imaging was conducted at baseline and at 15- and 30-min instillation. Results were compared to those of MBFM and periodic acid-Schiff (PAS) staining. A similar longitudinal study was performed in-vivo, and the outcomes were analyzed.

Results

qOBM accurately imaged polystyrene beads, with measured phase delays matching theoretical predictions. In normal mouse conjunctiva, qOBM visualized GCs in high contrast, confirmed by MBFM, and the average phase delay was 0.59 ± 0.25 radians. Under hyperosmotic stress, qOBM detected a significant reduction in GC phase delays, decreasing to levels of the surrounding tissue (−0.07 ± 0.14 radians). In normal conditions, no notable changes were observed in GCs. In-vivo imaging results were consistent with ex-vivo findings. Statistical analysis further characterized these changes. The results were consistent with MBFM and PAS staining.

Conclusions

qOBM is a high-contrast, label-free imaging modality that enables the functional assessment of GCs. This technique holds significant potential for advancing research and clinical diagnostics related to ocular surface diseases.

{"title":"Label-free quantitative imaging of conjunctival goblet cells","authors":"Noseong Park , Suil Jeon , Seonghan Kim , Jungbin Lee , Jin Suk Ryu , Wan Jae Choi , Chang Ho Yoon , Chulmin Joo , Ki Hean Kim","doi":"10.1016/j.jtos.2025.01.009","DOIUrl":"10.1016/j.jtos.2025.01.009","url":null,"abstract":"<div><h3>Purpose</h3><div>To introduce and validate quantitative oblique back-illumination microscopy (qOBM) as a label-free, high-contrast imaging technique for visualizing conjunctival goblet cells (GCs) and assessing their functional changes.</div></div><div><h3>Methods</h3><div>qOBM was developed in conjunction with moxifloxacin-based fluorescence microscopy (MBFM), which was used for validating GC imaging. Initial validation was conducted with polystyrene beads, followed by testing on normal mouse conjunctiva under both <em>ex-vivo</em> and <em>in-vivo</em> conditions. Longitudinal qOBM imaging was performed on <em>ex-vivo</em> mouse conjunctiva exposed to hyperosmotic stress (induced by 1000 mOsm/kg NaCl solution) and normal saline (300 mOsm/kg balanced salt solution, BSS). Imaging was conducted at baseline and at 15- and 30-min instillation. Results were compared to those of MBFM and periodic acid-Schiff (PAS) staining. A similar longitudinal study was performed <em>in-vivo</em>, and the outcomes were analyzed.</div></div><div><h3>Results</h3><div>qOBM accurately imaged polystyrene beads, with measured phase delays matching theoretical predictions. In normal mouse conjunctiva, qOBM visualized GCs in high contrast, confirmed by MBFM, and the average phase delay was 0.59 ± 0.25 radians. Under hyperosmotic stress, qOBM detected a significant reduction in GC phase delays, decreasing to levels of the surrounding tissue (−0.07 ± 0.14 radians). In normal conditions, no notable changes were observed in GCs. <em>In</em>-<em>vivo</em> imaging results were consistent with <em>ex-vivo</em> findings. Statistical analysis further characterized these changes. The results were consistent with MBFM and PAS staining.</div></div><div><h3>Conclusions</h3><div>qOBM is a high-contrast, label-free imaging modality that enables the functional assessment of GCs. This technique holds significant potential for advancing research and clinical diagnostics related to ocular surface diseases.</div></div>","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":"36 ","pages":"Pages 156-163"},"PeriodicalIF":5.9,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143043998","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}

引用次数: 0