Pub Date : 2025-06-20DOI: 10.1016/j.jtos.2025.06.006
Liyun Wang , Hongbo Yin , Yujia Yang , Li Qiu
Purpose
We employed 24 MHz ultrasonography to evaluate the morphological features of meibomian glands (MGs) and compared the ultrasonic differences in morphology between healthy volunteers and meibomian gland dysfunction (MGD) patients.
Methods
24 MHz ultrasound examinations on both the upper and lower eyelids of healthy volunteers and patients with MGD, using transverse and longitudinal sections. The reproducibility of ultrasonographic findings for the MG was evaluated, and a comparison of morphological characteristics at different examination sites between the two groups was made.
Results
Among 89 participants, 24 were healthy volunteers and 65 had MGD. The cross-sectional ultrasound findings showed well-organized punctate hyperechoic ducts within the tarsal plate, surrounded by hypoechoic acinar formations, which were further classified based on the extent of MG involvement into three categories: normal, ≤50 % involvement, and >50 % involvement. Additionally, a typical longitudinal ultrasound appearance of a MG consisted of a thin band-like hypoechoic structure (acinar) with uniform thickness accompanied by an arc-shaped linear hyperechoic duct in its middle region. Furthermore, seven abnormal longitudinal ultrasound manifestations were categorized as distortion, ectasia, central duct truncation, cyst formation, structureless appearance, complete disappearance or other findings. The intra- and inter-observer agreement for those categories was found to be high (ICC>0.6). MGD patients exhibited a higher likelihood of overall MG involvement or abnormal ultrasound findings, particularly in relation to the middle part of the upper eyelid.
Conclusion
The present study has developed an initial classification method to identify abnormalities in MG morphology using 24 MHz ultrasound in MGD patients.
{"title":"Ultrasonography assessments of meibomian gland as a noninvasive method of detecting changes in morphology","authors":"Liyun Wang , Hongbo Yin , Yujia Yang , Li Qiu","doi":"10.1016/j.jtos.2025.06.006","DOIUrl":"10.1016/j.jtos.2025.06.006","url":null,"abstract":"<div><h3>Purpose</h3><div>We employed 24 MHz ultrasonography to evaluate the morphological features of meibomian glands (MGs) and compared the ultrasonic differences in morphology between healthy volunteers and meibomian gland dysfunction (MGD) patients.</div></div><div><h3>Methods</h3><div>24 MHz ultrasound examinations on both the upper and lower eyelids of healthy volunteers and patients with MGD, using transverse and longitudinal sections. The reproducibility of ultrasonographic findings for the MG was evaluated, and a comparison of morphological characteristics at different examination sites between the two groups was made.</div></div><div><h3>Results</h3><div>Among 89 participants, 24 were healthy volunteers and 65 had MGD. The cross-sectional ultrasound findings showed well-organized punctate hyperechoic ducts within the tarsal plate, surrounded by hypoechoic acinar formations, which were further classified based on the extent of MG involvement into three categories: normal, ≤50 % involvement, and >50 % involvement. Additionally, a typical longitudinal ultrasound appearance of a MG consisted of a thin band-like hypoechoic structure (acinar) with uniform thickness accompanied by an arc-shaped linear hyperechoic duct in its middle region. Furthermore, seven abnormal longitudinal ultrasound manifestations were categorized as distortion, ectasia, central duct truncation, cyst formation, structureless appearance, complete disappearance or other findings. The intra- and inter-observer agreement for those categories was found to be high (ICC>0.6). MGD patients exhibited a higher likelihood of overall MG involvement or abnormal ultrasound findings, particularly in relation to the middle part of the upper eyelid.</div></div><div><h3>Conclusion</h3><div>The present study has developed an initial classification method to identify abnormalities in MG morphology using 24 MHz ultrasound in MGD patients.</div></div>","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":"38 ","pages":"Pages 72-79"},"PeriodicalIF":5.9,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144337791","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}
Pub Date : 2025-06-20DOI: 10.1016/j.jtos.2025.06.005
Soumen Sadhu , Isabelle Jalbert , Luz Palacios-Derflingher , Ali Alghamdi , Blanka Golebiowski , Fiona Stapleton
Purpose
To examine ocular surface epithelial immune cell (EIC) density and corneal nerve parameters between patients with dry eye disease (DED) compared to healthy controls with further comparisons between auto-immune - Sjӧgren Syndrome DED (SS-DED) and non-autoimmune – non-Sjӧgren Syndrome DED (NSS-DED) subtypes.
Methods
A systematic review and meta-analysis following PRISMA guidelines (Prospero-CRD42023446763) were conducted including studies reporting corneal and conjunctival EIC density and/or corneal nerve parameters in DED and healthy controls using in vivo confocal microscopy. Electronic databases – PubMed, Embase, Scopus, Web of Science were searched from inception to March 2025.
Results
The meta-analysis included 24 studies (n = 1060 DED, n = 521 controls) reporting EIC density, 30 studies reporting nerve length (CNL; n = 1450 DED, n = 643 controls) and 20 studies reporting nerve density (CND; n = 919 DED, n = 462 controls) in the central cornea. Studies of other ocular surface locations were insufficient for meta-analysis. Higher central corneal EIC density was evident in DED compared to controls (MD: 57.9 cells/mm2; 95 % CI: 43.3, 72.5; p < 0.001), and in, SS-DED compared to NSS-DED (51.0 cells/mm2; 95 % CI: 12.0, 90.0; p = 0.01). DED had lower CNL (−4.0 mm/mm2; 95 % CI: 5.2, −2.7; p < 0.001) and CND (−7.2 nerves/mm2; 95 % CI: 10.3, −4.1; p < 0.001) compared to controls. No significant differences in nerve parameters were found between SS-DED and NSS-DED subtypes (CNL: 95 % CI: 3.0, 1.4, CND: 6.8, 4.8; p ≥ 0.46).
Conclusion
DED involves substantial EIC infiltration and reduced corneal nerve parameters. SS-DED is distinguished by higher EIC density than NSS-DED, while no differences were observed in corneal nerve parameters.
{"title":"Ocular surface epithelial immune cells and corneal nerves in dry eye disease - A systematic review and meta-analysis of in vivo confocal microscopy data","authors":"Soumen Sadhu , Isabelle Jalbert , Luz Palacios-Derflingher , Ali Alghamdi , Blanka Golebiowski , Fiona Stapleton","doi":"10.1016/j.jtos.2025.06.005","DOIUrl":"10.1016/j.jtos.2025.06.005","url":null,"abstract":"<div><h3>Purpose</h3><div>To examine ocular surface epithelial immune cell (EIC) density and corneal nerve parameters between patients with dry eye disease (DED) compared to healthy controls with further comparisons between auto-immune - Sjӧgren Syndrome DED (SS-DED) and non-autoimmune – non-Sjӧgren Syndrome DED (NSS-DED) subtypes.</div></div><div><h3>Methods</h3><div>A systematic review and meta-analysis following PRISMA guidelines (Prospero-CRD42023446763) were conducted including studies reporting corneal and conjunctival EIC density and/or corneal nerve parameters in DED and healthy controls using <em>in vivo</em> confocal microscopy. Electronic databases – PubMed, Embase, Scopus, Web of Science were searched from inception to March 2025.</div></div><div><h3>Results</h3><div>The meta-analysis included 24 studies (n = 1060 DED, n = 521 controls) reporting EIC density, 30 studies reporting nerve length (CNL; n = 1450 DED, n = 643 controls) and 20 studies reporting nerve density (CND; n = 919 DED, n = 462 controls) in the central cornea. Studies of other ocular surface locations were insufficient for meta-analysis. Higher central corneal EIC density was evident in DED compared to controls (MD: 57.9 cells/mm<sup>2</sup>; 95 % CI: 43.3, 72.5; p < 0.001), and in, SS-DED compared to NSS-DED (51.0 cells/mm<sup>2</sup>; 95 % CI: 12.0, 90.0; p = 0.01). DED had lower CNL (−4.0 mm/mm<sup>2</sup>; 95 % CI: 5.2, −2.7; p < 0.001) and CND (−7.2 nerves/mm<sup>2</sup>; 95 % CI: 10.3, −4.1; p < 0.001) compared to controls. No significant differences in nerve parameters were found between SS-DED and NSS-DED subtypes (CNL: 95 % CI: 3.0, 1.4, CND: 6.8, 4.8; p ≥ 0.46).</div></div><div><h3>Conclusion</h3><div>DED involves substantial EIC infiltration and reduced corneal nerve parameters. SS-DED is distinguished by higher EIC density than NSS-DED, while no differences were observed in corneal nerve parameters.</div></div>","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":"38 ","pages":"Pages 80-96"},"PeriodicalIF":5.9,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144337790","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}
Pub Date : 2025-06-19DOI: 10.1016/j.jtos.2025.06.007
Ema V. Karakoleva , Nicholas Pondelis , Cameron Talbert , Mariela C. Aguilar , Alex Gonzalez , Cornelis Rowaan , Heather Durkee , Paula A. Sepulveda-Beltran , David Valdes-Arias , Chloe Shields , Shreya Bhatt , David Zurakowski , Deborah S. Jacobs , Joseph B. Ciolino , Elizabeth R. Felix , Jean-Marie Parel , Eric A. Moulton , Anat Galor
Purpose
To quantify visual photosensitivity discomfort thresholds (VPDT) in individuals with chronic ocular pain (COP) compared to controls without COP and explore relationships between VPDT, demographics, clinical factors, and ocular metrics.
Methods
Prospective case-control study of 75 participants: 36 with COP (age 46.5 ± 15.6 years; 56 % female) and 39 controls (39.2 ± 15.6 years; 56 % female). COP was defined by self-reported ocular pain intensity ≥15 on a numerical rating scale (range, 0–100) for ≥3 months. COP cases were subclassified into inflammatory (Sjögren's disease) and neuropathic ocular pain subgroups. VPDT was measured using the Ocular Photosensitivity Analyzer (OPA), and ocular symptoms were assessed using the Visual Light Sensitivity Questionnaire (VLSQ-8; 8–40) and Ocular Surface Disease Index (OSDI; 0–100), with OSDI Question 1 addressing light sensitivity (OSDI-Q1; 0–4).
Results
COP patients exhibited lower VPDT than controls (log lux, 1.60 ± 1.17 vs. 2.42 ± 1.05; P = 0.006), indicating greater photosensitivity discomfort. No differences in VPDT were seen across COP subtypes. COP patients also reported greater symptom severity than controls, with higher VLSQ-8 (21.92 ± 1.41 vs. 9.03 ± 0.53), OSDI (50.84 ± 3.88 vs. 2.82 ± 0.85), and OSDI-Q1 (2.00 ± 0.24 vs. 0.14 ± 0.06) scores (all P < 0.001). VPDT negatively correlated with VLSQ-8 (ρ = −0.75) and OSDI-Q1 (ρ = −0.62), demonstrating alignment between subjective light sensitivity symptoms and OPA-measured photosensitivity discomfort. Multivariable regression identified fibromyalgia as the strongest predictor of VPDT (19.6 % variance explained), with chronic fatigue improving the model (26.5 %).
Conclusion
COP subjects display greater photosensitivity-related discomfort than controls, highlighting the OPA's potential as a psychophysical tool for quantifying photoallodynia. Further research is needed to assess its diagnostic utility across COP subtypes.
{"title":"Heightened visual light sensitivity discomfort measured by the ocular photosensitivity analyzer is associated with chronic ocular pain","authors":"Ema V. Karakoleva , Nicholas Pondelis , Cameron Talbert , Mariela C. Aguilar , Alex Gonzalez , Cornelis Rowaan , Heather Durkee , Paula A. Sepulveda-Beltran , David Valdes-Arias , Chloe Shields , Shreya Bhatt , David Zurakowski , Deborah S. Jacobs , Joseph B. Ciolino , Elizabeth R. Felix , Jean-Marie Parel , Eric A. Moulton , Anat Galor","doi":"10.1016/j.jtos.2025.06.007","DOIUrl":"10.1016/j.jtos.2025.06.007","url":null,"abstract":"<div><h3>Purpose</h3><div>To quantify visual photosensitivity discomfort thresholds (VPDT) in individuals with chronic ocular pain (COP) compared to controls without COP and explore relationships between VPDT, demographics, clinical factors, and ocular metrics.</div></div><div><h3>Methods</h3><div>Prospective case-control study of 75 participants: 36 with COP (age 46.5 ± 15.6 years; 56 % female) and 39 controls (39.2 ± 15.6 years; 56 % female). COP was defined by self-reported ocular pain intensity ≥15 on a numerical rating scale (range, 0–100) for ≥3 months. COP cases were subclassified into inflammatory (Sjögren's disease) and neuropathic ocular pain subgroups. VPDT was measured using the Ocular Photosensitivity Analyzer (OPA), and ocular symptoms were assessed using the Visual Light Sensitivity Questionnaire (VLSQ-8; 8–40) and Ocular Surface Disease Index (OSDI; 0–100), with OSDI Question 1 addressing light sensitivity (OSDI-Q1; 0–4).</div></div><div><h3>Results</h3><div>COP patients exhibited lower VPDT than controls (log lux, 1.60 ± 1.17 vs. 2.42 ± 1.05; P = 0.006), indicating greater photosensitivity discomfort. No differences in VPDT were seen across COP subtypes. COP patients also reported greater symptom severity than controls, with higher VLSQ-8 (21.92 ± 1.41 vs. 9.03 ± 0.53), OSDI (50.84 ± 3.88 vs. 2.82 ± 0.85), and OSDI-Q1 (2.00 ± 0.24 vs. 0.14 ± 0.06) scores (all P < 0.001). VPDT negatively correlated with VLSQ-8 (ρ = −0.75) and OSDI-Q1 (ρ = −0.62), demonstrating alignment between subjective light sensitivity symptoms and OPA-measured photosensitivity discomfort. Multivariable regression identified fibromyalgia as the strongest predictor of VPDT (19.6 % variance explained), with chronic fatigue improving the model (26.5 %).</div></div><div><h3>Conclusion</h3><div>COP subjects display greater photosensitivity-related discomfort than controls, highlighting the OPA's potential as a psychophysical tool for quantifying photoallodynia. Further research is needed to assess its diagnostic utility across COP subtypes.</div></div>","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":"38 ","pages":"Pages 64-71"},"PeriodicalIF":5.9,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144337728","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}
Pub Date : 2025-06-18DOI: 10.1016/j.jtos.2025.06.004
Asha Parvathaneni , Liliya Benchetrit , Derek Metcalfe , James T. Kwan , Yandong Bian , Tavé Van Zyl , Hajirah N. Saeed , James Chodosh
Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) is an acute, severe immunobullous disorder of skin and mucous membranes that is most commonly induced by exposure to drugs. Causation of SJS/TEN is most often determined by the “algorithm of drug causality for epidermal necrolysis” (ALDEN) tool. However, concerns remain regarding the precision of ALDEN and causality assessment tools, potentially impacting ongoing studies attempting to link specific genotypes with specific drug classes as causes. To determine whether a standard of care exists in attribution of causation in SJS/TEN, we performed a narrative review of current concepts on causation in SJS/TEN, and available clinical and laboratory assessment tools for attributing causation. We found that current SJS/TEN causality attribution tools, including ALDEN, are somewhat limited by underlying assumptions. The utility of ex vivo tests proposed for determining causation in SJS/TEN, specifically the lymphocyte transformation test and cytokine stimulation assays, remain under investigation and are either not tractable for acute SJS/TEN or are not yet validated. In summary, a critical unmet need exists in the care of SJS/TEN patients, namely the difficulty in determining a precise cause in any specific individual. This shortfall limits the clinician's ability to discontinue only the causal agent in the acute phase, confounds studies of pathogenesis, and leaves affected patients in the chronic phase without knowing which drug or drug class is safe to use in the future. Further studies are needed to close this critical gap in the care of this devastating disease.
{"title":"Attribution of causality in Stevens-Johnson syndrome/toxic epidermal necrolysis","authors":"Asha Parvathaneni , Liliya Benchetrit , Derek Metcalfe , James T. Kwan , Yandong Bian , Tavé Van Zyl , Hajirah N. Saeed , James Chodosh","doi":"10.1016/j.jtos.2025.06.004","DOIUrl":"10.1016/j.jtos.2025.06.004","url":null,"abstract":"<div><div>Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) is an acute, severe immunobullous disorder of skin and mucous membranes that is most commonly induced by exposure to drugs. Causation of SJS/TEN is most often determined by the “algorithm of drug causality for epidermal necrolysis” (ALDEN) tool. However, concerns remain regarding the precision of ALDEN and causality assessment tools, potentially impacting ongoing studies attempting to link specific genotypes with specific drug classes as causes. To determine whether a standard of care exists in attribution of causation in SJS/TEN, we performed a narrative review of current concepts on causation in SJS/TEN, and available clinical and laboratory assessment tools for attributing causation. We found that current SJS/TEN causality attribution tools, including ALDEN, are somewhat limited by underlying assumptions. The utility of <em>ex vivo</em> tests proposed for determining causation in SJS/TEN, specifically the lymphocyte transformation test and cytokine stimulation assays, remain under investigation and are either not tractable for acute SJS/TEN or are not yet validated. In summary, a critical unmet need exists in the care of SJS/TEN patients, namely the difficulty in determining a precise cause in any specific individual. This shortfall limits the clinician's ability to discontinue only the causal agent in the acute phase, confounds studies of pathogenesis, and leaves affected patients in the chronic phase without knowing which drug or drug class is safe to use in the future. Further studies are needed to close this critical gap in the care of this devastating disease.</div></div>","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":"38 ","pages":"Pages 104-112"},"PeriodicalIF":5.9,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144337403","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}
Pub Date : 2025-06-14DOI: 10.1016/j.jtos.2025.06.002
Jay Ruzhang Jiang , Rima Khankan , William H. Ridder III , Andrew Loc Nguyen , Jerry R. Paugh
Purpose
To evaluate the safety and efficacy of eyelid androgen gel application to treat moderate to severe dry eye disease.
Methods
Twenty four eyes of 24 subjects (12 eyes per arm) were randomized to either eyelid testosterone or vehicle gel. Subjects received either 17β-Hydroxyandrost-4-en-3-one) 4.5 % wt./wt. or vehicle gel, applied twice daily 12 h apart for 4 weeks. Outcome parameters were monitored at 2-, and 4-weeks during dosing, and at 4-, and 8-weeks following dosing cessation.
Results
Significant positive differences were found in the androgen arm only, for Schein symptom score, tear meniscus height (TMH), fluorescein tear breakup time (fTBUT) and meibum score (repeated ANOVA, all p = 0.046 or less for each arm comparison) at all follow-up visits compared to baseline. For example, fTBUT in the androgen arm at 4 weeks was 6.2 ± 1.5 s compared to baseline, 3.3 ± 0.9 secs p< 0.001 (Dunnett's test, 95 % CI [1.838, 3.829]). No change was observed for either arm for staining, tear osmolarity, OSDI, non-invasive breakup time (NIBUT), serum lipid levels or hematocrit. Serum testosterone increased ∼ 9-fold in females (paired t-test; p = 0.006; CI [-240.2, −55.6]) in the androgen arm, but not males (paired t-test; p = 0.727; CI [-25.9, 31.2]).
Conclusions
Eyelid androgen gel application, 4.5 % wt./wt., was effective in improving tear fTBUT, symptoms, TMH and meibomian secretion grade in dry eye patients. Future research requires a larger sample size, outcome measure variability reduction and formulation optimization for absorption, androgen type, and dosing regimen.
目的评价眼睑雄激素凝胶治疗中重度干眼病的安全性和有效性。
{"title":"A pilot randomized controlled trial of topical androgen treatment in dry eye","authors":"Jay Ruzhang Jiang , Rima Khankan , William H. Ridder III , Andrew Loc Nguyen , Jerry R. Paugh","doi":"10.1016/j.jtos.2025.06.002","DOIUrl":"10.1016/j.jtos.2025.06.002","url":null,"abstract":"<div><h3>Purpose</h3><div>To evaluate the safety and efficacy of eyelid androgen gel application to treat moderate to severe dry eye disease.</div></div><div><h3>Methods</h3><div>Twenty four eyes of 24 subjects (12 eyes per arm) were randomized to either eyelid testosterone or vehicle gel. Subjects received either 17β-Hydroxyandrost-4-en-3-one) 4.5 % wt./wt. or vehicle gel, applied twice daily 12 h apart for 4 weeks. Outcome parameters were monitored at 2-, and 4-weeks during dosing, and at 4-, and 8-weeks following dosing cessation.</div></div><div><h3>Results</h3><div>Significant positive differences were found in the androgen arm only, for Schein symptom score, tear meniscus height (TMH), fluorescein tear breakup time (fTBUT) and meibum score (repeated ANOVA, all p = 0.046 or less for each arm comparison) at all follow-up visits compared to baseline. For example, fTBUT in the androgen arm at 4 weeks was 6.2 ± 1.5 s compared to baseline, 3.3 ± 0.9 secs p< 0.001 (Dunnett's test, 95 % CI [1.838, 3.829]). No change was observed for either arm for staining, tear osmolarity, OSDI, non-invasive breakup time (NIBUT), serum lipid levels or hematocrit. Serum testosterone increased ∼ 9-fold in females (paired <em>t</em>-test; p = 0.006; CI [-240.2, −55.6]) in the androgen arm, but not males (paired <em>t</em>-test; p = 0.727; CI [-25.9, 31.2]).</div></div><div><h3>Conclusions</h3><div>Eyelid androgen gel application, 4.5 % wt./wt., was effective in improving tear fTBUT, symptoms, TMH and meibomian secretion grade in dry eye patients. Future research requires a larger sample size, outcome measure variability reduction and formulation optimization for absorption, androgen type, and dosing regimen.</div></div>","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":"38 ","pages":"Pages 56-63"},"PeriodicalIF":5.9,"publicationDate":"2025-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144304682","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}
Pub Date : 2025-06-13DOI: 10.1016/j.jtos.2025.06.001
Barry Power , Michael T.M. Wang , Ally L. Xue , Jennifer P. Craig
{"title":"Association of tobacco smoking with aqueous deficient and evaporative dry eye disease subtypes: a prospective registry-based case-control study","authors":"Barry Power , Michael T.M. Wang , Ally L. Xue , Jennifer P. Craig","doi":"10.1016/j.jtos.2025.06.001","DOIUrl":"10.1016/j.jtos.2025.06.001","url":null,"abstract":"","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":"38 ","pages":"Pages 53-55"},"PeriodicalIF":5.9,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144304212","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}
Aniridia-associated keratopathy (AAK) is a progressive condition characterized by conjunctivalization of the cornea, yet its molecular mechanisms remain largely unknown. This study aims to elucidate the transcriptional landscape of AAK by characterizing the gene expression profiles of corneal epithelial cells in a patient with congenital aniridia.
Methods
Single-cell RNA sequencing (scRNA-seq) was performed on epithelial tissues collected from the clear central corneal region and limbus of a 48-year-old female patient with congenital aniridia. The transcriptomic profiles were compared with those of healthy control samples.
Results
scRNA-seq analysis revealed that a subpopulation of cells from the clear central corneal region expressed the cornea-specific keratins KRT3 and KRT12 despite a significant reduction in PAX6 expression. These cells exhibited corneal, conjunctival, or mixed gene signatures. Genes associated with wound healing and apoptosis were upregulated in the cornea-like cells from the aniridic cornea, indicating a chronic wound healing state. Elevated KLF4 expression and regulon activity were observed in these cornea-like cells. Most limbal epithelial cells exhibited conjunctiva-like characteristics, reflecting a loss of limbal cell identity.
Conclusion
While acknowledging the limitations of a single case study, this study provides deeper insights into the transcriptional signatures associated with AAK using scRNA-seq. We identified transcriptional alterations reflecting AAK progression and highlighted potential transcription factors that may contribute to corneal identity maintenance despite PAX6 deficiency. These findings enhance our understanding of AAK and suggest potential therapeutic strategies to slow its progression.
{"title":"Transcriptional landscape of aniridia-associated keratopathy through single-cell RNA sequencing","authors":"Masahito Yoshihara , Rei Kamuro , Susumu Hara , Nozomi Nishida , Koji Ohmoto , Yuzuru Sasamoto , Satoshi Kawasaki , Yoshinori Oie , Kohji Nishida","doi":"10.1016/j.jtos.2025.05.008","DOIUrl":"10.1016/j.jtos.2025.05.008","url":null,"abstract":"<div><h3>Purpose</h3><div>Aniridia-associated keratopathy (AAK) is a progressive condition characterized by conjunctivalization of the cornea, yet its molecular mechanisms remain largely unknown. This study aims to elucidate the transcriptional landscape of AAK by characterizing the gene expression profiles of corneal epithelial cells in a patient with congenital aniridia.</div></div><div><h3>Methods</h3><div>Single-cell RNA sequencing (scRNA-seq) was performed on epithelial tissues collected from the clear central corneal region and limbus of a 48-year-old female patient with congenital aniridia. The transcriptomic profiles were compared with those of healthy control samples.</div></div><div><h3>Results</h3><div>scRNA-seq analysis revealed that a subpopulation of cells from the clear central corneal region expressed the cornea-specific keratins <em>KRT3</em> and <em>KRT12</em> despite a significant reduction in <em>PAX6</em> expression. These cells exhibited corneal, conjunctival, or mixed gene signatures. Genes associated with wound healing and apoptosis were upregulated in the cornea-like cells from the aniridic cornea, indicating a chronic wound healing state. Elevated <em>KLF4</em> expression and regulon activity were observed in these cornea-like cells. Most limbal epithelial cells exhibited conjunctiva-like characteristics, reflecting a loss of limbal cell identity.</div></div><div><h3>Conclusion</h3><div>While acknowledging the limitations of a single case study, this study provides deeper insights into the transcriptional signatures associated with AAK using scRNA-seq. We identified transcriptional alterations reflecting AAK progression and highlighted potential transcription factors that may contribute to corneal identity maintenance despite PAX6 deficiency. These findings enhance our understanding of AAK and suggest potential therapeutic strategies to slow its progression.</div></div>","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":"38 ","pages":"Pages 43-52"},"PeriodicalIF":5.9,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144231411","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}
Pub Date : 2025-05-31DOI: 10.1016/j.jtos.2025.05.011
Marcel Y. Avila , Mario A. Jimenez-Mora , Edgar M. Espana
{"title":"Topical duloxetine for treatment of corneal keratinization in Aniridia-Associated Keratopathy","authors":"Marcel Y. Avila , Mario A. Jimenez-Mora , Edgar M. Espana","doi":"10.1016/j.jtos.2025.05.011","DOIUrl":"10.1016/j.jtos.2025.05.011","url":null,"abstract":"","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":"38 ","pages":"Pages 41-42"},"PeriodicalIF":5.9,"publicationDate":"2025-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144210614","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}
Pub Date : 2025-05-30DOI: 10.1016/j.jtos.2025.05.010
Hassan Mansoor , Isabelle Xin Yu Lee , Chang Liu , Mingyi Yu , Charmaine Jan Li Toh , Victor Wei-Tsu Hsu , Fengyi Liu , Daqian Lu , Thomas Chuen Lam , Hong Chang Tan , Lei Zhou , Yu-Chi Liu
Purpose
To investigate the efficacy of oral fenofibrate in the amelioration of ocular surface inflammation in diabetes mellitus (DM).
Methods
In this open-label interventional study, 41 participants with type 2 DM received oral fenofibrate for 30 days. Forty age-matched healthy controls were recruited. Ocular surface objective and subjective assessment, in-vivo confocal microscopy (IVCM) imaging and quantification for corneal dendritic cells (DCs), epithelium and neuromas were performed. Tear inflammatory markers and proteomics were analyzed with enzyme-linked immunosorbent assay (ELISA) and Data Independent Acquisition experiments before and after treatment.
Results
Oral fenofibrate treatment significantly improved tear film breakup time (p = 0.004), corneal staining evaluated with National Eye Institute-Corneal Fluorescein Staining scores (p = 0.005), and ocular surface symptoms assessed with the Ocular Surface Disease Index scores (p = 0.003), in DM patients. On IVCM, fenofibrate significantly reduced mean DC area (p = 0.01) and mean DC density (p = 0.02), while increasing mean DC elongation (p = 0.004) and length (p = 0.01), suggesting less DC activities. Fenofibrate also significantly increased corneal epithelial cell density (p = 0.04). 192 tear proteins were significantly altered after treatment. Fenofibrate significantly up-regulated the expression of anti-inflammatory interleukin-1 receptor antagonist, while significantly reduced the concentrations of pro-inflammatory and inflammatory proteins, including tumour necrosis factor α, nuclear factor kappa B, complement 4 B, cytochrome B5 Type A, and cytochrome B5 Type B (all p < 0.05) in tears, via regulation of tricarboxylic acid cycle, oxidative phosphorylation and liver X receptor/retinoid X receptor activation.
Conclusion
This first clinical trial demonstrated that oral fenofibrate ameliorates diabetic ocular surface inflammation, providing a novel therapeutic option for diabetic keratopathy.
{"title":"Fenofibrate ameliorates ocular surface inflammation in diabetic keratopathy","authors":"Hassan Mansoor , Isabelle Xin Yu Lee , Chang Liu , Mingyi Yu , Charmaine Jan Li Toh , Victor Wei-Tsu Hsu , Fengyi Liu , Daqian Lu , Thomas Chuen Lam , Hong Chang Tan , Lei Zhou , Yu-Chi Liu","doi":"10.1016/j.jtos.2025.05.010","DOIUrl":"10.1016/j.jtos.2025.05.010","url":null,"abstract":"<div><h3>Purpose</h3><div>To investigate the efficacy of oral fenofibrate in the amelioration of ocular surface inflammation in diabetes mellitus (DM).</div></div><div><h3>Methods</h3><div>In this open-label interventional study, 41 participants with type 2 DM received oral fenofibrate for 30 days. Forty age-matched healthy controls were recruited. Ocular surface objective and subjective assessment, in-vivo confocal microscopy (IVCM) imaging and quantification for corneal dendritic cells (DCs), epithelium and neuromas were performed. Tear inflammatory markers and proteomics were analyzed with enzyme-linked immunosorbent assay (ELISA) and Data Independent Acquisition experiments before and after treatment.</div></div><div><h3>Results</h3><div>Oral fenofibrate treatment significantly improved tear film breakup time (p = 0.004), corneal staining evaluated with National Eye Institute-Corneal Fluorescein Staining scores (p = 0.005), and ocular surface symptoms assessed with the Ocular Surface Disease Index scores (p = 0.003), in DM patients. On IVCM, fenofibrate significantly reduced mean DC area (p = 0.01) and mean DC density (p = 0.02), while increasing mean DC elongation (p = 0.004) and length (p = 0.01), suggesting less DC activities. Fenofibrate also significantly increased corneal epithelial cell density (p = 0.04). 192 tear proteins were significantly altered after treatment. Fenofibrate significantly up-regulated the expression of anti-inflammatory interleukin-1 receptor antagonist, while significantly reduced the concentrations of pro-inflammatory and inflammatory proteins, including tumour necrosis factor α, nuclear factor kappa B, complement 4 B, cytochrome B5 Type A, and cytochrome B5 Type B (all p < 0.05) in tears, via regulation of tricarboxylic acid cycle, oxidative phosphorylation and liver X receptor/retinoid X receptor activation.</div></div><div><h3>Conclusion</h3><div>This first clinical trial demonstrated that oral fenofibrate ameliorates diabetic ocular surface inflammation, providing a novel therapeutic option for diabetic keratopathy.</div></div>","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":"38 ","pages":"Pages 31-40"},"PeriodicalIF":5.9,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144195330","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}
Pub Date : 2025-05-23DOI: 10.1016/j.jtos.2025.05.009
Grace C. Tu , Farshad Abedi , Arthur Y. Chang , Xiang Shen , Mohammad Soleimani , Iskra Araujo , Rebecca Jung , Jeonghyun Kwon , Khandeker N. Anwar , Zohreh Arabpour , Nadim Mahmud , Elmer Y. Tu , Reza Dana , Peiman Hematti , Charlotte E. Joslin , Ali R. Djalilian
Purpose
To investigate the safety and tolerability of subconjunctival injection of three escalating doses of allogeneic bone marrow-derived mesenchymal stromal cells (MSCs) in patients with persistent corneal epithelial defect/disease (PCED).
Design
Prospective single-center open label phase 1b clinical trial.
Participants
Patients with PCED in the setting of neurotrophic keratitis and/or limbal stem cell deficiency.
Methods
A dose escalation study design was used. The first three patients received a subconjunctival injection of 1 × 106 MSCs/50 μL suspension; subsequently, three participants were treated with 1 subconjunctival injection of 3 × 106 MSCs/150 μL; and two participants received 2 subconjunctival injections of 3 × 106 MSCs/150 μl in 2 conjunctival sites.
Main outcome measures
The primary outcome was the safety of the treatment determined on day 28 post-injection. Ocular surface toxicity and other ocular or systemic treatment emergent adverse events (TEAEs) were assessed at 1, 7, 14, 28 and 90 days. Demonstration of safety on day 28 was required before escalating to the next higher dose. Changes in the PCED were also monitored.
Results
Eight participants completed the 90-day study. All 3 doses of subconjunctival MSCs were well tolerated. No participant developed ocular surface toxicity or other ocular or systemic TEAEs. The size of the PCED improved in 5 (63 %) patients; it increased in 2 (25 %) patients; and no progressive improvement was observed with dose escalation.
Conclusion
Subconjunctival administration of MSCs was safe and well tolerated with no systemic or ocular toxicity in patients with PCED. Improvement in epithelial defect size was observed in 63 % of the participants.
{"title":"Safety of subconjunctival injection of mesenchymal stromal cells in persistent corneal epithelial disease – A phase 1b clinical trial","authors":"Grace C. Tu , Farshad Abedi , Arthur Y. Chang , Xiang Shen , Mohammad Soleimani , Iskra Araujo , Rebecca Jung , Jeonghyun Kwon , Khandeker N. Anwar , Zohreh Arabpour , Nadim Mahmud , Elmer Y. Tu , Reza Dana , Peiman Hematti , Charlotte E. Joslin , Ali R. Djalilian","doi":"10.1016/j.jtos.2025.05.009","DOIUrl":"10.1016/j.jtos.2025.05.009","url":null,"abstract":"<div><h3>Purpose</h3><div>To investigate the safety and tolerability of subconjunctival injection of three escalating doses of allogeneic bone marrow-derived mesenchymal stromal cells (MSCs) in patients with persistent corneal epithelial defect/disease (PCED).</div></div><div><h3>Design</h3><div>Prospective single-center open label phase 1b clinical trial.</div></div><div><h3>Participants</h3><div>Patients with PCED in the setting of neurotrophic keratitis and/or limbal stem cell deficiency.</div></div><div><h3>Methods</h3><div>A dose escalation study design was used. The first three patients received a subconjunctival injection of 1 × 10<sup>6</sup> MSCs/50 μL suspension; subsequently, three participants were treated with 1 subconjunctival injection of 3 × 10<sup>6</sup> MSCs/150 μL; and two participants received 2 subconjunctival injections of 3 × 10<sup>6</sup> MSCs/150 μl in 2 conjunctival sites.</div></div><div><h3>Main outcome measures</h3><div>The primary outcome was the safety of the treatment determined on day 28 post-injection. Ocular surface toxicity and other ocular or systemic treatment emergent adverse events (TEAEs) were assessed at 1, 7, 14, 28 and 90 days. Demonstration of safety on day 28 was required before escalating to the next higher dose. Changes in the PCED were also monitored.</div></div><div><h3>Results</h3><div>Eight participants completed the 90-day study. All 3 doses of subconjunctival MSCs were well tolerated. No participant developed ocular surface toxicity or other ocular or systemic TEAEs. The size of the PCED improved in 5 (63 %) patients; it increased in 2 (25 %) patients; and no progressive improvement was observed with dose escalation.</div></div><div><h3>Conclusion</h3><div>Subconjunctival administration of MSCs was safe and well tolerated with no systemic or ocular toxicity in patients with PCED. Improvement in epithelial defect size was observed in 63 % of the participants.</div></div>","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":"38 ","pages":"Pages 8-13"},"PeriodicalIF":5.9,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144145335","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}