Glaucoma is a leading cause of irreversible blindness worldwide, characterized by optic nerve damage that is often associated with elevated intraocular pressure. Topical antiglaucoma medications, such as prostaglandin analogues, β-blockers, carbonic anhydrase inhibitors, α-adrenergic agonists, and Rho-kinase inhibitors, represent the mainstay of treatment; however, long-term therapy with these drugs is invariably associated with ADRs, including conjunctival hyperemia, ocular surface inflammation, Meibomian gland dysfunction, and tear film instability. These generally result from drug-induced structural and physiological changes in the conjunctiva, cornea, and tear film. In recent years, compelling evidence has emerged that supplementation with omega-3 fatty acids and hyaluronic acid can prevent and alleviate these ADRs. Omega-3 fatty acids suppress ocular surface inflammation, enhance tear film stability, and improve meibomian gland function, while HA enhances corneal healing, ocular surface lubrication, and epithelial regeneration. In addition, ocular barriers in the eye often impede the poor bioavailability of conventional topical medications, necessitating the development of NDDS. Nanoparticles, nanoemulsions, in-situ gels, and ocular inserts exhibit improved corneal permeability, prolonged retention time, and sustained drug release, thereby offering superior therapeutic outcomes with less local irritation. Combining omega-3 fatty acids and HA with NDDS may thus represent a new strategy to improve ocular drug delivery while minimizing ADRs associated with chronic antiglaucoma medications. This review highlights the mechanism underlying these side effects and discusses new opportunities to improve drug safety and compliance in long-term glaucoma management.
{"title":"Adverse effects of antiglaucoma medications: pathophysiology and novel drug delivery strategies for mitigation.","authors":"Monika Singh, Meena Devi, Pankaj Kumar, Monika, Rahul Singh, Vikas Jhawat","doi":"10.1007/s10792-026-03931-0","DOIUrl":"https://doi.org/10.1007/s10792-026-03931-0","url":null,"abstract":"<p><p>Glaucoma is a leading cause of irreversible blindness worldwide, characterized by optic nerve damage that is often associated with elevated intraocular pressure. Topical antiglaucoma medications, such as prostaglandin analogues, β-blockers, carbonic anhydrase inhibitors, α-adrenergic agonists, and Rho-kinase inhibitors, represent the mainstay of treatment; however, long-term therapy with these drugs is invariably associated with ADRs, including conjunctival hyperemia, ocular surface inflammation, Meibomian gland dysfunction, and tear film instability. These generally result from drug-induced structural and physiological changes in the conjunctiva, cornea, and tear film. In recent years, compelling evidence has emerged that supplementation with omega-3 fatty acids and hyaluronic acid can prevent and alleviate these ADRs. Omega-3 fatty acids suppress ocular surface inflammation, enhance tear film stability, and improve meibomian gland function, while HA enhances corneal healing, ocular surface lubrication, and epithelial regeneration. In addition, ocular barriers in the eye often impede the poor bioavailability of conventional topical medications, necessitating the development of NDDS. Nanoparticles, nanoemulsions, in-situ gels, and ocular inserts exhibit improved corneal permeability, prolonged retention time, and sustained drug release, thereby offering superior therapeutic outcomes with less local irritation. Combining omega-3 fatty acids and HA with NDDS may thus represent a new strategy to improve ocular drug delivery while minimizing ADRs associated with chronic antiglaucoma medications. This review highlights the mechanism underlying these side effects and discusses new opportunities to improve drug safety and compliance in long-term glaucoma management.</p>","PeriodicalId":14473,"journal":{"name":"International Ophthalmology","volume":"46 1","pages":"64"},"PeriodicalIF":1.4,"publicationDate":"2026-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146010491","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-20DOI: 10.1007/s10792-025-03915-6
Yingxin Qu, Xiaoqi Li, Qinghua Yang, Runpu Li, Ye Tao, Yifei Huang, Liqiang Wang
Purpose: Cataracts are associated with oxidative stress-induced damage to lens proteins. This study aims to identify differentially expressed proteins (DEPs) associated with the protective effects of hydrogen-rich saline (HRS) against N-methyl-N-nitrosourea (MNU)-induced cataracts, utilizing the antioxidant properties of hydrogen.
Methods: Sprague-Dawley rats were assigned to control, MNU-only, MNU + normal saline (NS), MNU + pirenoxine(PRX), and MNU + HRS groups. Cataracts were induced with MNU (postnatal day 15), and treatments (postnatal days 8-21) included intraperitoneal injections and eye drops. Cataract severity was assessed using slit-lamp examinations, Pentacam analysis, and spectrophotometry. Proteomic analysis of lens tissues from the MNU + HRS and MNU + NS groups employed tandem mass tag (TMT) labeling and mass spectrometry. DEPs were identified, grouped based on fold changes, and analyzed for Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG),, and domain enrichment. Parallel reaction monitoring (PRM) validated selected DEPs.
Results: HRS reduced MNU-induced cataract incidence to 50% versus 100% in MNU-only and NS groups and preserved lens clarity comparable to normal controls. Proteomic analysis identified 90 upregulated and 303 downregulated proteins in the HRS-treated group versus the NS-treated group. DEPs were enriched in GO terms related to ion transport, homeostasis, and ATP hydrolysis, as well as KEGG pathways like oxidative phosphorylation and arginine biosynthesis. Domain enrichment showed links to ATPase activity and energy metabolism. DEPs were grouped into Q1-Q4, with Q1 showing enrichment in oxidative phosphorylation and metabolic pathways. PRM confirmed the downregulation of 14 stress-response and metabolic proteins in the HRS-treated group.
Conclusion: HRS mitigates MNU-induced cataracts possibly by reducing oxidative stress and downregulating stress-response and metabolic proteins.
{"title":"Hydrogen-rich saline treatment modulates proteomic profiles to mitigate cataract development in a N-methyl-N-nitrosourea-induced rat model.","authors":"Yingxin Qu, Xiaoqi Li, Qinghua Yang, Runpu Li, Ye Tao, Yifei Huang, Liqiang Wang","doi":"10.1007/s10792-025-03915-6","DOIUrl":"10.1007/s10792-025-03915-6","url":null,"abstract":"<p><strong>Purpose: </strong>Cataracts are associated with oxidative stress-induced damage to lens proteins. This study aims to identify differentially expressed proteins (DEPs) associated with the protective effects of hydrogen-rich saline (HRS) against N-methyl-N-nitrosourea (MNU)-induced cataracts, utilizing the antioxidant properties of hydrogen.</p><p><strong>Methods: </strong>Sprague-Dawley rats were assigned to control, MNU-only, MNU + normal saline (NS), MNU + pirenoxine(PRX), and MNU + HRS groups. Cataracts were induced with MNU (postnatal day 15), and treatments (postnatal days 8-21) included intraperitoneal injections and eye drops. Cataract severity was assessed using slit-lamp examinations, Pentacam analysis, and spectrophotometry. Proteomic analysis of lens tissues from the MNU + HRS and MNU + NS groups employed tandem mass tag (TMT) labeling and mass spectrometry. DEPs were identified, grouped based on fold changes, and analyzed for Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG),, and domain enrichment. Parallel reaction monitoring (PRM) validated selected DEPs.</p><p><strong>Results: </strong>HRS reduced MNU-induced cataract incidence to 50% versus 100% in MNU-only and NS groups and preserved lens clarity comparable to normal controls. Proteomic analysis identified 90 upregulated and 303 downregulated proteins in the HRS-treated group versus the NS-treated group. DEPs were enriched in GO terms related to ion transport, homeostasis, and ATP hydrolysis, as well as KEGG pathways like oxidative phosphorylation and arginine biosynthesis. Domain enrichment showed links to ATPase activity and energy metabolism. DEPs were grouped into Q1-Q4, with Q1 showing enrichment in oxidative phosphorylation and metabolic pathways. PRM confirmed the downregulation of 14 stress-response and metabolic proteins in the HRS-treated group.</p><p><strong>Conclusion: </strong>HRS mitigates MNU-induced cataracts possibly by reducing oxidative stress and downregulating stress-response and metabolic proteins.</p>","PeriodicalId":14473,"journal":{"name":"International Ophthalmology","volume":"46 1","pages":"63"},"PeriodicalIF":1.4,"publicationDate":"2026-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12819484/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146010428","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-10DOI: 10.1007/s10792-025-03928-1
Wen Zhou, Sandeepani K Subasinghe, Francesc March de Ribot, Kelechi C Ogbuehi, George J Dias
Purpose: This review aims to summarize the current understanding of transepithelial corneal cross-linking (TE-CXL) for treating keratoconus (KC). It focuses on how TE-CXL compares with the standard epithelium-off cross-linking (S-CXL) and discusses recent improvements intended to make it more effective.
Methods: Relevant studies were reviewed from PubMed and Google Scholar. The review focused on research about new riboflavin solutions, delivery techniques, ultraviolet-A (UV-A) light settings, oxygen supply methods, and recent new technologies designed to improve the results of TE-CXL.
Results: TE-CXL preserves the corneal epithelium, providing better patient comfort and fewer postoperative complications. However, its corneal stiffening effect is generally lower than S-CXL due to limited riboflavin penetration and UV photoactivation. Recent approaches, including chemical enhancers, iontophoresis-assisted delivery, optimized UV-A protocols, nanotechnology-based or ultrasound-assisted methods have demonstrated potential to improve biomechanical strengthening. In addition, theranostic-guided TE-CXL, which provides real-time monitoring of stromal riboflavin concentration and adaptive UV-A dosing, represents a promising advancement. Nevertheless, differences in treatment protocols and in oxygen and luminance parameters still lead to variability in clinical outcomes.
Conclusions: TE-CXL is a promising and less invasive treatment for KC, offering better comfort and faster recovery. However, its long-term stability and biomechanical effect remain inferior to S-CXL. Future progress will depend on optimizing riboflavin and oxygen delivery, refining UV-A irradiation protocols, and validating newer technologies such as theranostic-guided CXL through large-scale clinical studies.
{"title":"Transepithelial corneal cross-linking: a review.","authors":"Wen Zhou, Sandeepani K Subasinghe, Francesc March de Ribot, Kelechi C Ogbuehi, George J Dias","doi":"10.1007/s10792-025-03928-1","DOIUrl":"10.1007/s10792-025-03928-1","url":null,"abstract":"<p><strong>Purpose: </strong>This review aims to summarize the current understanding of transepithelial corneal cross-linking (TE-CXL) for treating keratoconus (KC). It focuses on how TE-CXL compares with the standard epithelium-off cross-linking (S-CXL) and discusses recent improvements intended to make it more effective.</p><p><strong>Methods: </strong>Relevant studies were reviewed from PubMed and Google Scholar. The review focused on research about new riboflavin solutions, delivery techniques, ultraviolet-A (UV-A) light settings, oxygen supply methods, and recent new technologies designed to improve the results of TE-CXL.</p><p><strong>Results: </strong>TE-CXL preserves the corneal epithelium, providing better patient comfort and fewer postoperative complications. However, its corneal stiffening effect is generally lower than S-CXL due to limited riboflavin penetration and UV photoactivation. Recent approaches, including chemical enhancers, iontophoresis-assisted delivery, optimized UV-A protocols, nanotechnology-based or ultrasound-assisted methods have demonstrated potential to improve biomechanical strengthening. In addition, theranostic-guided TE-CXL, which provides real-time monitoring of stromal riboflavin concentration and adaptive UV-A dosing, represents a promising advancement. Nevertheless, differences in treatment protocols and in oxygen and luminance parameters still lead to variability in clinical outcomes.</p><p><strong>Conclusions: </strong>TE-CXL is a promising and less invasive treatment for KC, offering better comfort and faster recovery. However, its long-term stability and biomechanical effect remain inferior to S-CXL. Future progress will depend on optimizing riboflavin and oxygen delivery, refining UV-A irradiation protocols, and validating newer technologies such as theranostic-guided CXL through large-scale clinical studies.</p>","PeriodicalId":14473,"journal":{"name":"International Ophthalmology","volume":"46 1","pages":"62"},"PeriodicalIF":1.4,"publicationDate":"2026-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12790540/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145948528","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-07DOI: 10.1007/s10792-025-03896-6
Klemens Paul Kaiser, Jakob Wend, Myriam Böhm, Thomas Kohnen, Ingo Schmack
Purpose: To investigate wavefront aberrations, as well as corneal optical densitometry (COD), in eyes with epithelial basement membrane dystrophy (EBMD) and the influence on visual acuity.
Methods: In this cross-sectional study, 70 eyes of 70 patients (mean age 55.9 ± 14.0 years) with the central cornea involving EBMD were compared to 50 healthy eyes of 50 patients (mean age 58.8 ± 14.1 years) serving as controls. Wavefront aberrations of the anterior corneal surface and the total cornea were measured with the Pentacam AXL (Oculus Optikgeräte GmbH, Wetzlar, Germany), and calculated for the 6 mm central corneal zone. In addition, the COD (corneal light backscatter measured in grey scale units) of the anterior 120 µm of the central 0-2 mm, 2-6 mm, and 6-10 mm of the cornea was evaluated. Corrected distance visual acuity (CDVA) was correlated with wavefront aberrations and COD using Spearman correlation analysis.
Results: EBMD resulted in significant higher peak-to-valley (PTV; median: 15.0 [interquartile range: 9] µm), square root of the sum of the squared higher-order aberrations (RMS-HOA; 0.77 [0.52] µm), astigmatism (1.06 [1.04] µm), coma (0.41 [0.44] µm), and trefoil (0.28 [0.40] µm) (all p ≤ 0.01). A moderate correlation was found especially between CDVA and PTV as well as RMS-HOA. EBMD led to a statistically significant higher COD (p < 0.01) in the central corneal 6-mm and correlated moderately with CDVA outcomes.
Conclusions: Our study revealed a significant correlation between elevated wavefront aberrations and backscattering in eyes affected by epithelial basement membrane dystrophy. While COD demonstrates potential for diagnostic purposes, additional studies are necessary to ascertain its specificity and distinguish EBMD from other ocular surface disorders.
{"title":"Analysis of corneal wavefront aberrations and corneal densitometry in eyes with epithelial basement membrane dystrophy.","authors":"Klemens Paul Kaiser, Jakob Wend, Myriam Böhm, Thomas Kohnen, Ingo Schmack","doi":"10.1007/s10792-025-03896-6","DOIUrl":"10.1007/s10792-025-03896-6","url":null,"abstract":"<p><strong>Purpose: </strong>To investigate wavefront aberrations, as well as corneal optical densitometry (COD), in eyes with epithelial basement membrane dystrophy (EBMD) and the influence on visual acuity.</p><p><strong>Methods: </strong>In this cross-sectional study, 70 eyes of 70 patients (mean age 55.9 ± 14.0 years) with the central cornea involving EBMD were compared to 50 healthy eyes of 50 patients (mean age 58.8 ± 14.1 years) serving as controls. Wavefront aberrations of the anterior corneal surface and the total cornea were measured with the Pentacam AXL (Oculus Optikgeräte GmbH, Wetzlar, Germany), and calculated for the 6 mm central corneal zone. In addition, the COD (corneal light backscatter measured in grey scale units) of the anterior 120 µm of the central 0-2 mm, 2-6 mm, and 6-10 mm of the cornea was evaluated. Corrected distance visual acuity (CDVA) was correlated with wavefront aberrations and COD using Spearman correlation analysis.</p><p><strong>Results: </strong>EBMD resulted in significant higher peak-to-valley (PTV; median: 15.0 [interquartile range: 9] µm), square root of the sum of the squared higher-order aberrations (RMS-HOA; 0.77 [0.52] µm), astigmatism (1.06 [1.04] µm), coma (0.41 [0.44] µm), and trefoil (0.28 [0.40] µm) (all p ≤ 0.01). A moderate correlation was found especially between CDVA and PTV as well as RMS-HOA. EBMD led to a statistically significant higher COD (p < 0.01) in the central corneal 6-mm and correlated moderately with CDVA outcomes.</p><p><strong>Conclusions: </strong>Our study revealed a significant correlation between elevated wavefront aberrations and backscattering in eyes affected by epithelial basement membrane dystrophy. While COD demonstrates potential for diagnostic purposes, additional studies are necessary to ascertain its specificity and distinguish EBMD from other ocular surface disorders.</p>","PeriodicalId":14473,"journal":{"name":"International Ophthalmology","volume":"46 1","pages":"61"},"PeriodicalIF":1.4,"publicationDate":"2026-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12779729/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145911444","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-06DOI: 10.1007/s10792-025-03929-0
P Raghavan, C Balasubramanian, T Jarin
Background: Keratoconus (KCN) is a progressive degenerative corneal disorder characterized by corneal thinning and cone-shaped protrusion, leading to significant visual impairment if not detected early. Accurate staging of KCN using corneal topographic maps is critical for timely diagnosis and effective treatment planning.
Methods: This study proposes an enhanced deep learning framework for KCN stage classification based on corneal topographic images. The model employs a Dual Vision Transformer (DViT) to effectively capture both local and global spatial features. To optimize model performance, the Electric Eel Foraging Optimizer (EEFO) is utilized for tuning attention weights and hyperparameters of the DViT architecture. Additionally, model interpretability is enhanced through Local Interpretable Model-Agnostic Explanations (LIME) and SHapley Additive exPlanations (SHAP), enabling visualization of corneal regions influencing classification decisions.
Results: Experimental evaluations conducted on a keratoconus dataset demonstrate that the proposed DViT-EEFO model outperforms existing approaches, achieving an accuracy of 99.2%, recall of 99.3%, and precision of 99.5%. Interpretability analyses confirm that the model focuses on clinically relevant corneal regions during decision-making.
Conclusion: The proposed DViT-EEFO framework delivers high classification performance and improved interpretability, highlighting its strong potential as a reliable clinical decision support tool for early keratoconus diagnosis and treatment planning.
{"title":"Dual vision transformer with bio-inspired optimization for explainable keratoconus classification.","authors":"P Raghavan, C Balasubramanian, T Jarin","doi":"10.1007/s10792-025-03929-0","DOIUrl":"https://doi.org/10.1007/s10792-025-03929-0","url":null,"abstract":"<p><strong>Background: </strong>Keratoconus (KCN) is a progressive degenerative corneal disorder characterized by corneal thinning and cone-shaped protrusion, leading to significant visual impairment if not detected early. Accurate staging of KCN using corneal topographic maps is critical for timely diagnosis and effective treatment planning.</p><p><strong>Methods: </strong>This study proposes an enhanced deep learning framework for KCN stage classification based on corneal topographic images. The model employs a Dual Vision Transformer (DViT) to effectively capture both local and global spatial features. To optimize model performance, the Electric Eel Foraging Optimizer (EEFO) is utilized for tuning attention weights and hyperparameters of the DViT architecture. Additionally, model interpretability is enhanced through Local Interpretable Model-Agnostic Explanations (LIME) and SHapley Additive exPlanations (SHAP), enabling visualization of corneal regions influencing classification decisions.</p><p><strong>Results: </strong>Experimental evaluations conducted on a keratoconus dataset demonstrate that the proposed DViT-EEFO model outperforms existing approaches, achieving an accuracy of 99.2%, recall of 99.3%, and precision of 99.5%. Interpretability analyses confirm that the model focuses on clinically relevant corneal regions during decision-making.</p><p><strong>Conclusion: </strong>The proposed DViT-EEFO framework delivers high classification performance and improved interpretability, highlighting its strong potential as a reliable clinical decision support tool for early keratoconus diagnosis and treatment planning.</p>","PeriodicalId":14473,"journal":{"name":"International Ophthalmology","volume":"46 1","pages":"60"},"PeriodicalIF":1.4,"publicationDate":"2026-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145911457","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-06DOI: 10.1007/s10792-025-03911-w
Hui Di Khor, Jun Fai Yap, Yi Wen Lim, Tajunisah Iqbal, Penny P W Lott
Purpose: To evaluate subclinical retinal microvascular changes in long-term hydroxychloroquine (HCQ) users (≥ 5 years) using optical coherence tomography angiography (OCTA), comparing retinal parameters with a healthy control group.
Method: This single-center, case-control study involved 118 participants (comprising of 59 HCQ users and 59 controls) who underwent comprehensive ophthalmic evaluations, including OCTA to assess the foveal avascular zone (FAZ), macular vessel density (VD) in superficial and deep capillary plexus (SCP and DCP), and retinal thickness. Statistical tests included independent t, Mann-Whitney U, and Spearman's rank correlation tests, with significance set at p < 0.05.
Results: Most HCQ users were female (88.14%) with a median age of 47 years, primarily treated for systemic lupus erythematosus (SLE), receiving a mean HCQ dose of 5.14 mg/kg/day. FAZ area and central foveal thickness (CFT) did not differ significantly between groups. However, parafoveal and perifoveal retinal thickness was significantly reduced in the HCQ group (p < 0.001). Macular VD was significantly higher in the foveal and parafoveal DCP among HCQ users (p < 0.001).
Conclusion: Long-term HCQ use is associated with significant parafoveal and perifoveal retinal thinning, with variable OCTA microvascular changes. These findings highlight the potential role of OCTA in early detection of HCQ-induced retinal alterations.
{"title":"Optical coherence tomography angiography parameters in patients on hydroxychloroquine therapy.","authors":"Hui Di Khor, Jun Fai Yap, Yi Wen Lim, Tajunisah Iqbal, Penny P W Lott","doi":"10.1007/s10792-025-03911-w","DOIUrl":"https://doi.org/10.1007/s10792-025-03911-w","url":null,"abstract":"<p><strong>Purpose: </strong>To evaluate subclinical retinal microvascular changes in long-term hydroxychloroquine (HCQ) users (≥ 5 years) using optical coherence tomography angiography (OCTA), comparing retinal parameters with a healthy control group.</p><p><strong>Method: </strong>This single-center, case-control study involved 118 participants (comprising of 59 HCQ users and 59 controls) who underwent comprehensive ophthalmic evaluations, including OCTA to assess the foveal avascular zone (FAZ), macular vessel density (VD) in superficial and deep capillary plexus (SCP and DCP), and retinal thickness. Statistical tests included independent t, Mann-Whitney U, and Spearman's rank correlation tests, with significance set at p < 0.05.</p><p><strong>Results: </strong>Most HCQ users were female (88.14%) with a median age of 47 years, primarily treated for systemic lupus erythematosus (SLE), receiving a mean HCQ dose of 5.14 mg/kg/day. FAZ area and central foveal thickness (CFT) did not differ significantly between groups. However, parafoveal and perifoveal retinal thickness was significantly reduced in the HCQ group (p < 0.001). Macular VD was significantly higher in the foveal and parafoveal DCP among HCQ users (p < 0.001).</p><p><strong>Conclusion: </strong>Long-term HCQ use is associated with significant parafoveal and perifoveal retinal thinning, with variable OCTA microvascular changes. These findings highlight the potential role of OCTA in early detection of HCQ-induced retinal alterations.</p>","PeriodicalId":14473,"journal":{"name":"International Ophthalmology","volume":"46 1","pages":"59"},"PeriodicalIF":1.4,"publicationDate":"2026-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145911563","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Purpose: To synthesize recent (2020-2025) advances on how gut, oral, and ocular-surface microbiota contribute to major blinding eye diseases, dry eye disease (DED), non-infectious uveitis, glaucoma, optic neuropathy, age-related macular degeneration (AMD), and diabetic retinopathy (DR), and to evaluate the therapeutic potential of microbiome-based interventions.
Methods: PubMed and Web of Science were searched (January 2020-October 2025) using the terms "gut microbiota", "ocular diseases", and "immunomodulatory therapies". Eligible studies included original human and animal research demonstrating microbial dysbiosis or testing microbiome-directed therapies. Data were synthesized thematically across microbial composition, immune-metabolic mechanisms, and intervention outcomes.
Results: Across all six diseases, dysbiosis was consistently characterized by depletion of anti-inflammatory taxa such as Akkermansia, Ruminococcaceae, and other short-chain fatty acid (SCFA) producers, with enrichment of pro-inflammatory bacteria including Proteobacteria, Staphylococcus, and Porphyromonas gingivalis. These changes were associated with increased intestinal permeability, systemic lipopolysaccharide (LPS) and trimethylamine N-oxide (TMAO), Th17 (T helper 17)/Treg (regulatory T cell) imbalance, and loss of SCFA-mediated neuroprotection. Probiotics containing Lactobacillus or Bifidobacterium improved tear stability and reduced inflammation in preclinical and pilot clinical studies, while high-fiber diets ameliorated lesions in age-related macular degeneration (AMD) and diabetic retinopathy (DR). Fecal microbiota transplantation confirmed microbial causality but revealed donor-dependent effects, and engineered Lactobacillus expressing angiotensin-converting enzyme 2 (ACE2) or Ang-(1-7) preserved retinal integrity in diabetic models.
Conclusions: Microbial dysbiosis acts as a common driver of immune-metabolic dysfunction in blinding eye diseases. Microbiome-targeted strategies show promising efficacy in experimental systems, but large, longitudinal human trials are needed for clinical translation.
目的:综合近期(2020-2025)肠道、口腔和眼表微生物群对主要致盲性眼病、干眼病(DED)、非感染性葡萄膜炎、青光眼、视神经病变、年龄相关性黄斑变性(AMD)和糖尿病视网膜病变(DR)的影响,并评估基于微生物组的干预措施的治疗潜力。方法:检索PubMed和Web of Science(2020年1月- 2025年10月),检索词为“肠道微生物群”、“眼部疾病”和“免疫调节疗法”。符合条件的研究包括证明微生物生态失调或测试微生物组导向疗法的原始人类和动物研究。数据按主题综合了微生物组成、免疫代谢机制和干预结果。结果:在所有六种疾病中,生态失调的特征始终是抗炎类群(如Akkermansia, Ruminococcaceae和其他短链脂肪酸(SCFA)生产者)的消耗,促炎细菌(包括变形杆菌,葡萄球菌和牙龈卟啉单胞菌)的富集。这些变化与肠道通透性增加、全身性脂多糖(LPS)和三甲胺n -氧化物(TMAO)、Th17(辅助性T细胞17)/Treg(调节性T细胞)失衡以及scfa介导的神经保护功能丧失有关。在临床前和试点临床研究中,含有乳酸杆菌或双歧杆菌的益生菌改善了眼泪稳定性并减少了炎症,而高纤维饮食改善了年龄相关性黄斑变性(AMD)和糖尿病视网膜病变(DR)的病变。粪便微生物群移植证实了微生物的因果关系,但显示了供体依赖效应,表达血管紧张素转换酶2 (ACE2)或Ang-(1-7)的工程乳酸杆菌在糖尿病模型中保持了视网膜完整性。结论:在致盲性眼病中,微生物生态失调是免疫代谢功能障碍的共同驱动因素。针对微生物组的策略在实验系统中显示出有希望的功效,但临床转化需要大规模的纵向人体试验。
{"title":"The gut-eye axis in blinding eye diseases: microbiota-driven immune dysregulation and immunomodulatory therapies.","authors":"Chuyao Wang, Hongyu Li, Ting Wang, Xiuyun Li, Jianwei Liu, Aijun Deng, Xinwei Jiao","doi":"10.1007/s10792-025-03921-8","DOIUrl":"https://doi.org/10.1007/s10792-025-03921-8","url":null,"abstract":"<p><strong>Purpose: </strong>To synthesize recent (2020-2025) advances on how gut, oral, and ocular-surface microbiota contribute to major blinding eye diseases, dry eye disease (DED), non-infectious uveitis, glaucoma, optic neuropathy, age-related macular degeneration (AMD), and diabetic retinopathy (DR), and to evaluate the therapeutic potential of microbiome-based interventions.</p><p><strong>Methods: </strong>PubMed and Web of Science were searched (January 2020-October 2025) using the terms \"gut microbiota\", \"ocular diseases\", and \"immunomodulatory therapies\". Eligible studies included original human and animal research demonstrating microbial dysbiosis or testing microbiome-directed therapies. Data were synthesized thematically across microbial composition, immune-metabolic mechanisms, and intervention outcomes.</p><p><strong>Results: </strong>Across all six diseases, dysbiosis was consistently characterized by depletion of anti-inflammatory taxa such as Akkermansia, Ruminococcaceae, and other short-chain fatty acid (SCFA) producers, with enrichment of pro-inflammatory bacteria including Proteobacteria, Staphylococcus, and Porphyromonas gingivalis. These changes were associated with increased intestinal permeability, systemic lipopolysaccharide (LPS) and trimethylamine N-oxide (TMAO), Th17 (T helper 17)/Treg (regulatory T cell) imbalance, and loss of SCFA-mediated neuroprotection. Probiotics containing Lactobacillus or Bifidobacterium improved tear stability and reduced inflammation in preclinical and pilot clinical studies, while high-fiber diets ameliorated lesions in age-related macular degeneration (AMD) and diabetic retinopathy (DR). Fecal microbiota transplantation confirmed microbial causality but revealed donor-dependent effects, and engineered Lactobacillus expressing angiotensin-converting enzyme 2 (ACE2) or Ang-(1-7) preserved retinal integrity in diabetic models.</p><p><strong>Conclusions: </strong>Microbial dysbiosis acts as a common driver of immune-metabolic dysfunction in blinding eye diseases. Microbiome-targeted strategies show promising efficacy in experimental systems, but large, longitudinal human trials are needed for clinical translation.</p>","PeriodicalId":14473,"journal":{"name":"International Ophthalmology","volume":"46 1","pages":"57"},"PeriodicalIF":1.4,"publicationDate":"2025-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145849973","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-29DOI: 10.1007/s10792-025-03930-7
Javier Fernández-Torres, Yessica Zamudio-Cuevas, Karina Martínez-Flores
Background: Ankylosing spondylitis (AS) is a chronic inflammatory disease with a strong genetic component, frequently accompanied by extra-articular manifestations such as acute anterior uveitis (AAU). This study aimed to evaluate the association of the rs11362 and rs1800972 (DEFB1), and rs3806268 and rs10754558 (NLRP3) gene variants in AS patients with and without AAU.
Methods: A case control-study was conducted on 58 patients with AS and 70 healthy controls. Genotyping was performed using the TaqMan® SNP Genotyping Assay. Genotype frequencies were compared between studied groups and subgroups, and associations were estimated by logistic regression models. Interactions between these variants were also evaluated.
Results: In the case-control analysis after adjusment, the TT (rs11362) and CC (rs1800972) genotypes of the DEFB1 gene were significantly associated with an increased risk of AS (OR = 6.89, 95% CI = 1.66-28.4, p = 0.008 and OR = 3.43, 95% CI = 1.02-11.5, p = 0.046, respectively). Then, in the subanalysis, the GC (rs1800972) genotype was associated with an increased risk of AAU (OR = 9.93, 95% CI = 1.76-55.7, p = 0.009). No significant associations were observed for NLRP3 polymorphisms individually. However, a strong interaction between rs1800972 and rs3806268 polymorphisms was observed (entropy = 22.95%).
Conclusions: These results suggest that DEFB1 gene variants (rs11362 and rs1800972) are associated with an increased risk of developing AS. Specifically, rs1800972 is associated with increased susceptibility to AAU. While NLRP3 variants did not show significant associations independently, their interaction with DEFB1 variants suggests a possible synergistic effect on AAU development.
背景:强直性脊柱炎(AS)是一种具有强烈遗传成分的慢性炎症性疾病,常伴有关节外表现,如急性前葡萄膜炎(AAU)。本研究旨在评估rs11362和rs1800972 (DEFB1)、rs3806268和rs10754558 (NLRP3)基因变异在合并和不合并AAU的AS患者中的相关性。方法:对58例AS患者和70例健康对照者进行病例对照研究。采用TaqMan®SNP基因分型法进行基因分型。比较各组和亚组之间的基因型频率,并通过逻辑回归模型估计相关性。还评估了这些变体之间的相互作用。结果:在调整后的病例对照分析中,DEFB1基因TT (rs11362)和CC (rs1800972)基因型与AS风险增加显著相关(OR = 6.89, 95% CI = 1.66 ~ 28.4, p = 0.008; OR = 3.43, 95% CI = 1.02 ~ 11.5, p = 0.046)。然后,在亚组分析中,GC (rs1800972)基因型与AAU风险增加相关(OR = 9.93, 95% CI = 1.76-55.7, p = 0.009)。未观察到NLRP3多态性的显著相关性。rs1800972多态性与rs3806268多态性之间存在强交互作用(熵值为22.95%)。结论:这些结果表明,DEFB1基因变异(rs11362和rs1800972)与患AS的风险增加有关。具体来说,rs1800972与AAU易感性增加相关。虽然NLRP3变异没有单独显示出显著的相关性,但它们与DEFB1变异的相互作用表明,它们可能对AAU的发展产生协同作用。
{"title":"DEFB1 and NLRP3 gene variants are associated with acute anterior uveitis in ankylosing spondylitis: evidence of an innate immune interaction axis.","authors":"Javier Fernández-Torres, Yessica Zamudio-Cuevas, Karina Martínez-Flores","doi":"10.1007/s10792-025-03930-7","DOIUrl":"https://doi.org/10.1007/s10792-025-03930-7","url":null,"abstract":"<p><strong>Background: </strong>Ankylosing spondylitis (AS) is a chronic inflammatory disease with a strong genetic component, frequently accompanied by extra-articular manifestations such as acute anterior uveitis (AAU). This study aimed to evaluate the association of the rs11362 and rs1800972 (DEFB1), and rs3806268 and rs10754558 (NLRP3) gene variants in AS patients with and without AAU.</p><p><strong>Methods: </strong>A case control-study was conducted on 58 patients with AS and 70 healthy controls. Genotyping was performed using the TaqMan® SNP Genotyping Assay. Genotype frequencies were compared between studied groups and subgroups, and associations were estimated by logistic regression models. Interactions between these variants were also evaluated.</p><p><strong>Results: </strong>In the case-control analysis after adjusment, the TT (rs11362) and CC (rs1800972) genotypes of the DEFB1 gene were significantly associated with an increased risk of AS (OR = 6.89, 95% CI = 1.66-28.4, p = 0.008 and OR = 3.43, 95% CI = 1.02-11.5, p = 0.046, respectively). Then, in the subanalysis, the GC (rs1800972) genotype was associated with an increased risk of AAU (OR = 9.93, 95% CI = 1.76-55.7, p = 0.009). No significant associations were observed for NLRP3 polymorphisms individually. However, a strong interaction between rs1800972 and rs3806268 polymorphisms was observed (entropy = 22.95%).</p><p><strong>Conclusions: </strong>These results suggest that DEFB1 gene variants (rs11362 and rs1800972) are associated with an increased risk of developing AS. Specifically, rs1800972 is associated with increased susceptibility to AAU. While NLRP3 variants did not show significant associations independently, their interaction with DEFB1 variants suggests a possible synergistic effect on AAU development.</p>","PeriodicalId":14473,"journal":{"name":"International Ophthalmology","volume":"46 1","pages":"58"},"PeriodicalIF":1.4,"publicationDate":"2025-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145849981","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-29DOI: 10.1007/s10792-025-03895-7
Neel Edupuganti, Haley Chishom, Tommy Bui, Danny Alevy, Tae Jin Lee, Mathilde Franklin, Marc Töteberg-Harms
Purpose: This study evaluates the impact of medical versus combined medical and surgical glaucoma treatments on patients' quality of life (QoL). While both approaches reduce intraocular pressure, research shows mixed effects on QoL. Given updated clinical guidelines and the gap in QoL-focused glaucoma management, this study applies validated QoL measures to assess treatment effects and inform patient-centered care.
Methods: From June to October 2023, 180 patients at Augusta University Eye Care Center completed the 25-item National Eye Institute Visual Function Questionnaire (NEI VFQ-25) and Glaucoma Profile Instrument (GPI) surveys. Chart reviews provided demographic and clinical data, including glaucoma status and treatment. QoL scores were calculated using validated algorithms. Associations between clinical variables and QoL outcomes were analyzed using ANOVA and t-tests in R 4.4.1.
Results: Among 180 patients, 103 had glaucoma or were suspects. 64% of glaucoma patients received medical treatment only, and 34% received combined medical and surgical treatment. VFQ-25 scores differed significantly by race (p = 0.0489), severity (p = 0.0001), and age (p = 0.0459), but not by gender, glaucoma status, or treatment. Severe glaucoma patients had the lowest QoL. Severity strongly impacted GPI scores (p = 0.0092) and multiple VFQ-25 domains. Differences by treatment modality were observed only in the driving subscale (p = 0.0378). No significant differences were observed in overall QoL scores between treatment groups.
Conclusion: No significant vision-related QoL differences were found between treatment groups. Most patients were medically managed, possibly reflecting limited QoL benefit from surgery. QoL correlated more with disease severity than treatment modality or demographics. These findings highlight a disconnect between current treatment strategies and patient-perceived outcomes, underscoring the need for innovative strategies to improve QoL in glaucoma care.
{"title":"The impact of treatment modality on quality of life in glaucoma patients: findings from a clinical survey study in Augusta, GA.","authors":"Neel Edupuganti, Haley Chishom, Tommy Bui, Danny Alevy, Tae Jin Lee, Mathilde Franklin, Marc Töteberg-Harms","doi":"10.1007/s10792-025-03895-7","DOIUrl":"10.1007/s10792-025-03895-7","url":null,"abstract":"<p><strong>Purpose: </strong>This study evaluates the impact of medical versus combined medical and surgical glaucoma treatments on patients' quality of life (QoL). While both approaches reduce intraocular pressure, research shows mixed effects on QoL. Given updated clinical guidelines and the gap in QoL-focused glaucoma management, this study applies validated QoL measures to assess treatment effects and inform patient-centered care.</p><p><strong>Methods: </strong>From June to October 2023, 180 patients at Augusta University Eye Care Center completed the 25-item National Eye Institute Visual Function Questionnaire (NEI VFQ-25) and Glaucoma Profile Instrument (GPI) surveys. Chart reviews provided demographic and clinical data, including glaucoma status and treatment. QoL scores were calculated using validated algorithms. Associations between clinical variables and QoL outcomes were analyzed using ANOVA and t-tests in R 4.4.1.</p><p><strong>Results: </strong>Among 180 patients, 103 had glaucoma or were suspects. 64% of glaucoma patients received medical treatment only, and 34% received combined medical and surgical treatment. VFQ-25 scores differed significantly by race (p = 0.0489), severity (p = 0.0001), and age (p = 0.0459), but not by gender, glaucoma status, or treatment. Severe glaucoma patients had the lowest QoL. Severity strongly impacted GPI scores (p = 0.0092) and multiple VFQ-25 domains. Differences by treatment modality were observed only in the driving subscale (p = 0.0378). No significant differences were observed in overall QoL scores between treatment groups.</p><p><strong>Conclusion: </strong>No significant vision-related QoL differences were found between treatment groups. Most patients were medically managed, possibly reflecting limited QoL benefit from surgery. QoL correlated more with disease severity than treatment modality or demographics. These findings highlight a disconnect between current treatment strategies and patient-perceived outcomes, underscoring the need for innovative strategies to improve QoL in glaucoma care.</p>","PeriodicalId":14473,"journal":{"name":"International Ophthalmology","volume":"46 1","pages":"55"},"PeriodicalIF":1.4,"publicationDate":"2025-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12748089/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145849987","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Purpose: This study aims to systematically evaluate the consistency of total keratometry (TK) and posterior keratometry (PK) measurements obtained by the IOL Master 700 and Pentacam in cataract patients with varying axial lengths (AL).
Methods: A total of 240 cataract patients (240 eyes) were recruited from Beijing Tongren Hospital between February and April 2025. Participants were categorized into six groups based on AL: < 22 mm, 22-24 mm, 24-26 mm, 26-28 mm, 28-30 mm, and ≥ 30 mm. All patients underwent preoperative examinations using the IOL Master 700 and Pentacam systems to obtain measurements of TK and PK. The paired t-test or Wilcoxon signed-rank test was employed to evaluate intergroup differences. The Bland-Altman analysis was conducted to assess the 95% limits of agreement (LoA), with calculation of the mean difference.
Results: Except for the subgroup with AL < 22 mm, the TK measured by the IOL Master 700 was significantly higher than that obtained using the Pentacam across all AL subgroups. The mean difference ranged from 0.005D to 0.406 D, with the width of the 95% LoA varying between 1.071D and 2.382D. For PK, measurements obtained by the IOLMaster 700 were significantly flatter compared to those from the Pentacam across all subgroups. The mean differences ranged from 0.442 to 0.478 D, with the width of the 95% LoA ranging from 0.244 to 0.319 D.
Conclusion: Regardless of AL, the measurement discrepancies in TK and PK between the two devices exceed the clinically acceptable limits, suggesting that these devices are not interchangeable across patients with varying AL.
{"title":"Agreement between IOL Master 700 and Pentacam in measuring total keratometry and posterior keratometry across different axial lengths in cataract patients.","authors":"Zhi-Yong Tian, Peng Zhao, Zhong-Yan Li, Zhi Chen, Jing-Shang Zhang, Ying-Yan Mao, Xiu-Hua Wan, Meng Li","doi":"10.1007/s10792-025-03922-7","DOIUrl":"10.1007/s10792-025-03922-7","url":null,"abstract":"<p><strong>Purpose: </strong>This study aims to systematically evaluate the consistency of total keratometry (TK) and posterior keratometry (PK) measurements obtained by the IOL Master 700 and Pentacam in cataract patients with varying axial lengths (AL).</p><p><strong>Methods: </strong>A total of 240 cataract patients (240 eyes) were recruited from Beijing Tongren Hospital between February and April 2025. Participants were categorized into six groups based on AL: < 22 mm, 22-24 mm, 24-26 mm, 26-28 mm, 28-30 mm, and ≥ 30 mm. All patients underwent preoperative examinations using the IOL Master 700 and Pentacam systems to obtain measurements of TK and PK. The paired t-test or Wilcoxon signed-rank test was employed to evaluate intergroup differences. The Bland-Altman analysis was conducted to assess the 95% limits of agreement (LoA), with calculation of the mean difference.</p><p><strong>Results: </strong>Except for the subgroup with AL < 22 mm, the TK measured by the IOL Master 700 was significantly higher than that obtained using the Pentacam across all AL subgroups. The mean difference ranged from 0.005D to 0.406 D, with the width of the 95% LoA varying between 1.071D and 2.382D. For PK, measurements obtained by the IOLMaster 700 were significantly flatter compared to those from the Pentacam across all subgroups. The mean differences ranged from 0.442 to 0.478 D, with the width of the 95% LoA ranging from 0.244 to 0.319 D.</p><p><strong>Conclusion: </strong>Regardless of AL, the measurement discrepancies in TK and PK between the two devices exceed the clinically acceptable limits, suggesting that these devices are not interchangeable across patients with varying AL.</p>","PeriodicalId":14473,"journal":{"name":"International Ophthalmology","volume":"46 1","pages":"56"},"PeriodicalIF":1.4,"publicationDate":"2025-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145849978","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}