Pub Date : 2026-01-01Epub Date: 2025-11-24DOI: 10.1016/j.preteyeres.2025.101417
Indumathi Singh , Ann M. Poynten , Arun V. Krishnan , Mark D.P. Willcox , Maria Markoulli
Type 2 diabetes is a chronic, systemic, metabolic disorder characterized by persistent hyperglycemia and associated with a broad spectrum of complications, including those affecting the ocular surface. This article reviews the structural, biochemical, and neuropathic changes observed in the ocular surface of patients with diabetes. Hyperglycemia and associated metabolic imbalances lead to tear film instability, inflammation, oxidative stress, and peripheral neuropathy, contributing to the pathogenesis of dry eye disease, impaired corneal wound healing and corneal neuropathy. In addition, systemic factors such as glycemic control, inflammatory cytokines, and microvascular impairment have direct impact on ocular surface homeostasis. This review also evaluates the effects of antidiabetic therapies on the ocular surface. Recent studies suggest that drugs such as metformin, sodium-glucose co-transporter 2 inhibitors, glucagon like peptide-1 receptor agonists, and insulin along with glucose control, may offer the ocular surface protective benefits. Evidence supports their roles in reducing ocular surface inflammation, promoting corneal nerve regeneration, and improving tear film homeostasis. A comprehensive understanding of these factors may facilitate improved screening, early diagnosis, and integrative management of ocular surface disorders in type 2 diabetes.
{"title":"The ocular surface in type 2 diabetes: pathophysiology and impact of anti-diabetic drugs","authors":"Indumathi Singh , Ann M. Poynten , Arun V. Krishnan , Mark D.P. Willcox , Maria Markoulli","doi":"10.1016/j.preteyeres.2025.101417","DOIUrl":"10.1016/j.preteyeres.2025.101417","url":null,"abstract":"<div><div>Type 2 diabetes is a chronic, systemic, metabolic disorder characterized by persistent hyperglycemia and associated with a broad spectrum of complications, including those affecting the ocular surface. This article reviews the structural, biochemical, and neuropathic changes observed in the ocular surface of patients with diabetes. Hyperglycemia and associated metabolic imbalances lead to tear film instability, inflammation, oxidative stress, and peripheral neuropathy, contributing to the pathogenesis of dry eye disease, impaired corneal wound healing and corneal neuropathy. In addition, systemic factors such as glycemic control, inflammatory cytokines, and microvascular impairment have direct impact on ocular surface homeostasis. This review also evaluates the effects of antidiabetic therapies on the ocular surface. Recent studies suggest that drugs such as metformin, sodium-glucose co-transporter 2 inhibitors, glucagon like peptide-1 receptor agonists, and insulin along with glucose control, may offer the ocular surface protective benefits. Evidence supports their roles in reducing ocular surface inflammation, promoting corneal nerve regeneration, and improving tear film homeostasis. A comprehensive understanding of these factors may facilitate improved screening, early diagnosis, and integrative management of ocular surface disorders in type 2 diabetes.</div></div>","PeriodicalId":21159,"journal":{"name":"Progress in Retinal and Eye Research","volume":"110 ","pages":"Article 101417"},"PeriodicalIF":14.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145592820","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 : 2026-01-01Epub Date: 2025-12-04DOI: 10.1016/j.preteyeres.2025.101421
Christiana Dinah , Marieh Esmaeelpour , Aleksandra V. Rachitskaya , Gabriella De Salvo , Marion R. Munk
There is an unmet need in patients with geographic atrophy (GA) for treatments that preserve and improve functional vision to maintain their independence and quality of life. The limited number of available treatments for GA have demonstrated structural benefits, but none have consistently shown significant functional outcomes in clinical trials. Currently, best-corrected visual acuity (BCVA) is considered the gold standard functional endpoint in clinical trials; however, in the case of GA, it cannot fully evaluate visual impairment or treatment response, particularly in fovea-sparing GA lesions. In addition, BCVA may not fully capture the functional impact of foveal and parafoveal scotomas. There is emerging evidence for the utility of other functional assessments that may provide a more robust representation of the functional impact of GA; however, the current utilization of these tests in GA clinical trials varies widely. This review aims to evaluate current functional endpoints in GA and their strengths and limitations based on characteristics such as strength of structure–function correlation, practicality and feasibility, and patient perspective. There are many factors to consider when choosing a functional vision assessment when designing a GA clinical trial, and each functional vision assessment has several advantages and disadvantages, which are summarized in this review article.
{"title":"Functional endpoints in patients with geographic atrophy: What to consider when designing a clinical trial","authors":"Christiana Dinah , Marieh Esmaeelpour , Aleksandra V. Rachitskaya , Gabriella De Salvo , Marion R. Munk","doi":"10.1016/j.preteyeres.2025.101421","DOIUrl":"10.1016/j.preteyeres.2025.101421","url":null,"abstract":"<div><div>There is an unmet need in patients with geographic atrophy (GA) for treatments that preserve and improve functional vision to maintain their independence and quality of life. The limited number of available treatments for GA have demonstrated structural benefits, but none have consistently shown significant functional outcomes in clinical trials. Currently, best-corrected visual acuity (BCVA) is considered the gold standard functional endpoint in clinical trials; however, in the case of GA, it cannot fully evaluate visual impairment or treatment response, particularly in fovea-sparing GA lesions. In addition, BCVA may not fully capture the functional impact of foveal and parafoveal scotomas. There is emerging evidence for the utility of other functional assessments that may provide a more robust representation of the functional impact of GA; however, the current utilization of these tests in GA clinical trials varies widely. This review aims to evaluate current functional endpoints in GA and their strengths and limitations based on characteristics such as strength of structure–function correlation, practicality and feasibility, and patient perspective. There are many factors to consider when choosing a functional vision assessment when designing a GA clinical trial, and each functional vision assessment has several advantages and disadvantages, which are summarized in this review article.</div></div>","PeriodicalId":21159,"journal":{"name":"Progress in Retinal and Eye Research","volume":"110 ","pages":"Article 101421"},"PeriodicalIF":14.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145689329","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 : 2026-01-01Epub Date: 2025-12-23DOI: 10.1016/j.preteyeres.2025.101432
Liusi Yang , Siyi Chen , Jiayun Ge , Zhitong Chen , Kuangqi Chen , Jiahui Li , Jiaxin Zhang , Ya Li , Mingli Qu , Dawn J.H. Neo , Xuhong Zhang , Xiang Li , Yinhao Wang , Qianjie Yang , Xiangzheng Zhang , Dongjie Song , Xiuyi Li , Lin Du , Ye Shen , Weiyun Shi , Jianping Tong
The cornea is the eye's outermost protective and refractive barrier whose physiological homeostasis depends on mitochondrial competence and dynamic stability. Mitochondrial dysfunctions are characterized by impaired electron transport chain efficiency, excessive reactive oxygen species generation, calcium dysregulation, and disrupted dynamics. Clinically, mitochondrial dysfunctions underlie the pathogenesis of diverse corneal disorders, including Fuchs endothelial corneal dystrophy, dry eye disease, diabetic keratopathy, keratoconus and infectious keratitis. Although prior work has linked mitochondrial dysfunction to corneal pathology, an integrated, mechanism-to-therapy synthesis remains limited. Dysregulated mitochondrial redox signaling exacerbates oxidative stress and the release of mitochondrial-derived damage-associated molecular patterns, triggering inflammatory cascades and cell death pathways. Imbalances in mitochondrial metabolism and dynamics further amplify cellular damage and disease progression. This review systematically delineates mitochondria's roles in corneal energy supply and homeostatic regulation, clarifies the causal involvement of mitochondrial dysfunction and dysregulated networks in corneal disease pathogenesis. More importantly, by elucidating the intricate mechanisms of mitochondrial regulation and dysfunction, this review underscores the transformative potential of mitochondria-targeted interventions in advancing corneal disease management and improving clinical outcome.
{"title":"Mitochondria in corneal physiology and pathology: A mechanistic perspective","authors":"Liusi Yang , Siyi Chen , Jiayun Ge , Zhitong Chen , Kuangqi Chen , Jiahui Li , Jiaxin Zhang , Ya Li , Mingli Qu , Dawn J.H. Neo , Xuhong Zhang , Xiang Li , Yinhao Wang , Qianjie Yang , Xiangzheng Zhang , Dongjie Song , Xiuyi Li , Lin Du , Ye Shen , Weiyun Shi , Jianping Tong","doi":"10.1016/j.preteyeres.2025.101432","DOIUrl":"10.1016/j.preteyeres.2025.101432","url":null,"abstract":"<div><div>The cornea is the eye's outermost protective and refractive barrier whose physiological homeostasis depends on mitochondrial competence and dynamic stability. Mitochondrial dysfunctions are characterized by impaired electron transport chain efficiency, excessive reactive oxygen species generation, calcium dysregulation, and disrupted dynamics. Clinically, mitochondrial dysfunctions underlie the pathogenesis of diverse corneal disorders, including Fuchs endothelial corneal dystrophy, dry eye disease, diabetic keratopathy, keratoconus and infectious keratitis. Although prior work has linked mitochondrial dysfunction to corneal pathology, an integrated, mechanism-to-therapy synthesis remains limited. Dysregulated mitochondrial redox signaling exacerbates oxidative stress and the release of mitochondrial-derived damage-associated molecular patterns, triggering inflammatory cascades and cell death pathways. Imbalances in mitochondrial metabolism and dynamics further amplify cellular damage and disease progression. This review systematically delineates mitochondria's roles in corneal energy supply and homeostatic regulation, clarifies the causal involvement of mitochondrial dysfunction and dysregulated networks in corneal disease pathogenesis. More importantly, by elucidating the intricate mechanisms of mitochondrial regulation and dysfunction, this review underscores the transformative potential of mitochondria-targeted interventions in advancing corneal disease management and improving clinical outcome.</div></div>","PeriodicalId":21159,"journal":{"name":"Progress in Retinal and Eye Research","volume":"110 ","pages":"Article 101432"},"PeriodicalIF":14.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145822819","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 : 2026-01-01Epub Date: 2025-11-27DOI: 10.1016/j.preteyeres.2025.101420
Yousef A. Fouad , Lorenzo Bianco , Prithvi Ramtohul , Sara Touhami , Rishi Gupta , Saeed Mohammadi , Francesco Bandello , Elisabetta Miserocchi , Lee Merrill Jampol , Maria Vittoria Cicinelli
Multiple Evanescent White Dot Syndrome (MEWDS) is a primary outer retinal inflammatory disorder, classically presenting as an acute, unilateral, self-limiting condition in young to middle-aged adults. It is characterized by multiple small white spots at the posterior pole, foveal granularity, wreath-like hyperfluorescence on fluorescein angiography, and a “dot-over-spot” hypofluorescent pattern on late-phase indocyanine green angiography. This PRISMA-compliant systematic review analyzed 592 eyes from 240 publications, supplemented by an institutional case series. While most cases conformed to the typical phenotype (62 %), nearly one-third were atypical (20 %) or secondary (18 %) to other chorioretinal diseases. Atypical forms included bilateral or recurrent presentations, distinctive angiographic patterns, or absence of spontaneous recovery with permanent structural damage. We also identified a previously unreported phenotype in older adults, featuring confluent hyperautofluorescence extending into the mid-periphery and hyperreflective outer retinal lesions, often with subacute worsening and partial steroid responsiveness. Secondary MEWDS occurred in association with various chorioretinal disorders, most commonly punctate inner choroiditis. Collectively, these findings support viewing MEWDS within the broader spectrum of outer retinal disorders sharing photoreceptor pathology but differing in triggers, imaging signatures, and outcomes. Recognition of atypical and secondary variants is essential for accurate diagnosis, risk stratification, and tailored management.
{"title":"Multiple evanescent white dot syndrome: Typical, atypical, and secondary variants","authors":"Yousef A. Fouad , Lorenzo Bianco , Prithvi Ramtohul , Sara Touhami , Rishi Gupta , Saeed Mohammadi , Francesco Bandello , Elisabetta Miserocchi , Lee Merrill Jampol , Maria Vittoria Cicinelli","doi":"10.1016/j.preteyeres.2025.101420","DOIUrl":"10.1016/j.preteyeres.2025.101420","url":null,"abstract":"<div><div>Multiple Evanescent White Dot Syndrome (MEWDS) is a primary outer retinal inflammatory disorder, classically presenting as an acute, unilateral, self-limiting condition in young to middle-aged adults. It is characterized by multiple small white spots at the posterior pole, foveal granularity, wreath-like hyperfluorescence on fluorescein angiography, and a “dot-over-spot” hypofluorescent pattern on late-phase indocyanine green angiography. This PRISMA-compliant systematic review analyzed 592 eyes from 240 publications, supplemented by an institutional case series. While most cases conformed to the typical phenotype (62 %), nearly one-third were atypical (20 %) or secondary (18 %) to other chorioretinal diseases. Atypical forms included bilateral or recurrent presentations, distinctive angiographic patterns, or absence of spontaneous recovery with permanent structural damage. We also identified a previously unreported phenotype in older adults, featuring confluent hyperautofluorescence extending into the mid-periphery and hyperreflective outer retinal lesions, often with subacute worsening and partial steroid responsiveness. Secondary MEWDS occurred in association with various chorioretinal disorders, most commonly punctate inner choroiditis. Collectively, these findings support viewing MEWDS within the broader spectrum of outer retinal disorders sharing photoreceptor pathology but differing in triggers, imaging signatures, and outcomes. Recognition of atypical and secondary variants is essential for accurate diagnosis, risk stratification, and tailored management.</div></div>","PeriodicalId":21159,"journal":{"name":"Progress in Retinal and Eye Research","volume":"110 ","pages":"Article 101420"},"PeriodicalIF":14.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145611702","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 : 2025-11-01Epub Date: 2025-10-16DOI: 10.1016/j.preteyeres.2025.101410
Jason C. Yam , Xiu Juan Zhang , Ebenezer Zaabaar , Yuyao Wang , Yuelan Gao , Yuzhou Zhang , Xiaotong Li , Ka Wai Kam , Fangyao Tang , Wai Kit Chu , Xiangtian Zhou , Wei Zhang , Xiangui He , Pei-Chang Wu , Kathryn A. Rose , Ian Morgan , Mingguang He , Kyoko Ohno-Matsui , Jost B. Jonas , Mingzhi Zhang , Chi Pui Pang
The alarming increase in childhood myopia has emerged as a significant public health concern. Due to its long-term consequences, there is also an expanding interest in adult-onset myopia. This review provides a comprehensive summary of interventions for slowing the onset and progression of myopia and discusses factors influencing their efficacy. Outdoor time is an effective intervention for at-risk pre-myopes, which can reduce myopia onset by up to 50 % and has been implemented on a large scale in some countries through school reforms. 0.05 % atropine and repeated low-level red light (RLRL) have also shown the potential to prevent myopia onset by approximately 50 %, though the cost-benefit of implementing them on a large scale warrants more research. Low-concentration atropine, various designs of peripheral defocus spectacles, contact lenses, and RLRL effectively slow myopia progression by at least 50 %. A history of higher baseline myopia status, faster baseline progression, parental myopia, high-risk lifestyle, and less outdoor time requires rigorous interventions. When combined with RLRL or atropine concentrations higher than 0.025 %, orthokeratology significantly improves myopia control in fast progressors and/or high myopes. Combining low-concentration atropine with peripheral defocus glasses or dual-focus contact lenses also yields better efficacy than monotherapy. There is limited research on adult myopia control, but offering comprehensive lifestyle and visual environment recommendations remains essential. Consistent use of these interventions and thorough safety monitoring are crucial for building clinical confidence. The success of myopia control hinges on personalization, given the diverse factors influencing efficacy and the challenges of large-scale implementation.
{"title":"Interventions to reduce incidence and progression of myopia in children and adults","authors":"Jason C. Yam , Xiu Juan Zhang , Ebenezer Zaabaar , Yuyao Wang , Yuelan Gao , Yuzhou Zhang , Xiaotong Li , Ka Wai Kam , Fangyao Tang , Wai Kit Chu , Xiangtian Zhou , Wei Zhang , Xiangui He , Pei-Chang Wu , Kathryn A. Rose , Ian Morgan , Mingguang He , Kyoko Ohno-Matsui , Jost B. Jonas , Mingzhi Zhang , Chi Pui Pang","doi":"10.1016/j.preteyeres.2025.101410","DOIUrl":"10.1016/j.preteyeres.2025.101410","url":null,"abstract":"<div><div>The alarming increase in childhood myopia has emerged as a significant public health concern. Due to its long-term consequences, there is also an expanding interest in adult-onset myopia. This review provides a comprehensive summary of interventions for slowing the onset and progression of myopia and discusses factors influencing their efficacy. Outdoor time is an effective intervention for at-risk pre-myopes, which can reduce myopia onset by up to 50 % and has been implemented on a large scale in some countries through school reforms. 0.05 % atropine and repeated low-level red light (RLRL) have also shown the potential to prevent myopia onset by approximately 50 %, though the cost-benefit of implementing them on a large scale warrants more research. Low-concentration atropine, various designs of peripheral defocus spectacles, contact lenses, and RLRL effectively slow myopia progression by at least 50 %. A history of higher baseline myopia status, faster baseline progression, parental myopia, high-risk lifestyle, and less outdoor time requires rigorous interventions. When combined with RLRL or atropine concentrations higher than 0.025 %, orthokeratology significantly improves myopia control in fast progressors and/or high myopes. Combining low-concentration atropine with peripheral defocus glasses or dual-focus contact lenses also yields better efficacy than monotherapy. There is limited research on adult myopia control, but offering comprehensive lifestyle and visual environment recommendations remains essential. Consistent use of these interventions and thorough safety monitoring are crucial for building clinical confidence. The success of myopia control hinges on personalization, given the diverse factors influencing efficacy and the challenges of large-scale implementation.</div></div>","PeriodicalId":21159,"journal":{"name":"Progress in Retinal and Eye Research","volume":"109 ","pages":"Article 101410"},"PeriodicalIF":14.7,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145318493","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 : 2025-11-01Epub Date: 2025-10-28DOI: 10.1016/j.preteyeres.2025.101411
MD Imam Uddin
Oxygen is the major element for metabolism in the retina. Reduced oxygen supply causes significant changes in cellular metabolism and gene expression in the retina initiating inflammasome activation, apoptosis of retinal cells, mitochondrial damage, oxidative stress and neurodegeneration. Physiologically, retinal hypoxia plays important role regulating vasculogenesis during our development in early life. Retinal hypoxia also plays key regulatory roles during the onset and progression of many retinopathy conditions including neovascularization at later stages of our life. Though the exact mechanism of neovascularization is still largely unknown, hypoxia may contribute to the over expression of vascular endothelial growth factor (VEGF), and VEGF is a known inducer of neovascularization. Thus, molecular imaging of retinal hypoxia could be an important diagnostic tool assessing the risk of retinopathy, its progression, and response to therapy. Imaging retinal hypoxia is also an important diagnostic tool assessing the risk of inflammasome activation, mitochondrial damage, oxidative stress and apoptosis of retinal cells at molecular levels. This review will provide an overview of technologies to detect retinal hypoxia in the living retinal tissues before the onset of tissue damage. This review will also discuss the design and development of HYPOX-4, a highly sensitive molecular imaging probe capable of detecting retinal hypoxia in the living retina before the onset of neovascularization. The author will further discuss a quantitative method to assess HYPOX-4 fluorescence intensity measurement by computational methods, correlating with levels of retinal hypoxia and create a predictive biomarker for retinal neovascularization. An overview of the technology development will also include Dr. Linsenmeier's early development of microelectrode for our fundamental understanding of retinal tissue oxygenation using an invasive measurement technique. An overview of the other emerging technologies, including retinal oximetry, phosphorescence lifetime imaging and photoacoustic imaging will be discussed.
{"title":"Imaging of the retinal hypoxia: A journey from oxygen microelectrode to the first hypoxia imaging in the living retina","authors":"MD Imam Uddin","doi":"10.1016/j.preteyeres.2025.101411","DOIUrl":"10.1016/j.preteyeres.2025.101411","url":null,"abstract":"<div><div>Oxygen is the major element for metabolism in the retina. Reduced oxygen supply causes significant changes in cellular metabolism and gene expression in the retina initiating inflammasome activation, apoptosis of retinal cells, mitochondrial damage, oxidative stress and neurodegeneration. Physiologically, retinal hypoxia plays important role regulating vasculogenesis during our development in early life. Retinal hypoxia also plays key regulatory roles during the onset and progression of many retinopathy conditions including neovascularization at later stages of our life. Though the exact mechanism of neovascularization is still largely unknown, hypoxia may contribute to the over expression of vascular endothelial growth factor (VEGF), and VEGF is a known inducer of neovascularization. Thus, molecular imaging of retinal hypoxia could be an important diagnostic tool assessing the risk of retinopathy, its progression, and response to therapy. Imaging retinal hypoxia is also an important diagnostic tool assessing the risk of inflammasome activation, mitochondrial damage, oxidative stress and apoptosis of retinal cells at molecular levels. This review will provide an overview of technologies to detect retinal hypoxia in the living retinal tissues before the onset of tissue damage. This review will also discuss the design and development of HYPOX-4, a highly sensitive molecular imaging probe capable of detecting retinal hypoxia in the living retina before the onset of neovascularization. The author will further discuss a quantitative method to assess HYPOX-4 fluorescence intensity measurement by computational methods, correlating with levels of retinal hypoxia and create a predictive biomarker for retinal neovascularization. An overview of the technology development will also include Dr. Linsenmeier's early development of microelectrode for our fundamental understanding of retinal tissue oxygenation using an invasive measurement technique. An overview of the other emerging technologies, including retinal oximetry, phosphorescence lifetime imaging and photoacoustic imaging will be discussed.</div></div>","PeriodicalId":21159,"journal":{"name":"Progress in Retinal and Eye Research","volume":"109 ","pages":"Article 101411"},"PeriodicalIF":14.7,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145383788","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 : 2025-11-01Epub Date: 2025-09-20DOI: 10.1016/j.preteyeres.2025.101399
Elena Borzova , Steffen Heegaard , Elke O. Kreps , Vanessa Smith , Maurizio Cutolo , Enzo Berardesca , Erika Ponzini , Stephanie M. Willerth , Christopher J. Corrigan , Alain Taïeb , Werner Aberer , Riichiro Abe , Howard I. Maibach , Jacob P. Thyssen
Background
Eyelid dermatitis (ED) is an interdisciplinary medical challenge affecting thousands of patients worldwide. ED management can be difficult in view of the numerous differential diagnoses and limited treatment options. We review the diagnostic work-up for ED patients, with a special focus on the latest innovative solutions.
Observations
The diagnostic work-up of ED should include medical history, exposure analysis (direct contact, transfer by hands, airborne exposure, rarely ingestion) ocular complaints, clinical severity scores for eyelid manifestations, and consider general and specialized scoring systems. Patch testing and Schirmer test modifications can be used to delineate the underlying aetiology and to narrow the ED differential diagnosis. Metal release assays (nickel spot test, cobalt spot test) as well as gold jewelry avoidance can inform on clinically relevant metal allergy in selected cases. Repeated open application tests with cosmetic products can be used on the retroauricular skin. Transepidermal water loss (TEWL) measurements should be adapted for the eyelids. Further research on eyelid microbiome and transcriptomic biomarkers in the tear fluid and/or eyelid keratinocytes is required. Atopy patch testing with house dust mites (HDMs) can be helpful in selected cases but needs further standardization. Machine learning algorithms may aid image analysis for automated patch test readings and may leverage transcriptomic data for diagnostic classifications, particularly in ambiguous cases, and treatment monitoring in ED.
Conclusions and relevance
ED diagnosis can be challenging and may require the collaboration of ophthalmologists, dermatologists, allergists, and rheumatologists. Diagnostic innovations exist but their value in the diagnostic work-up is currently unclear.
{"title":"Eyelid dermatitis: Work-up and future diagnostic innovative solutions","authors":"Elena Borzova , Steffen Heegaard , Elke O. Kreps , Vanessa Smith , Maurizio Cutolo , Enzo Berardesca , Erika Ponzini , Stephanie M. Willerth , Christopher J. Corrigan , Alain Taïeb , Werner Aberer , Riichiro Abe , Howard I. Maibach , Jacob P. Thyssen","doi":"10.1016/j.preteyeres.2025.101399","DOIUrl":"10.1016/j.preteyeres.2025.101399","url":null,"abstract":"<div><h3>Background</h3><div>Eyelid dermatitis (ED) is an interdisciplinary medical challenge affecting thousands of patients worldwide. ED management can be difficult in view of the numerous differential diagnoses and limited treatment options. We review the diagnostic work-up for ED patients, with a special focus on the latest innovative solutions.</div></div><div><h3>Observations</h3><div>The diagnostic work-up of ED should include medical history, exposure analysis (direct contact, transfer by hands, airborne exposure, rarely ingestion) ocular complaints, clinical severity scores for eyelid manifestations, and consider general and specialized scoring systems. Patch testing and Schirmer test modifications can be used to delineate the underlying aetiology and to narrow the ED differential diagnosis. Metal release assays (nickel spot test, cobalt spot test) as well as gold jewelry avoidance can inform on clinically relevant metal allergy in selected cases. Repeated open application tests with cosmetic products can be used on the retroauricular skin. Transepidermal water loss (TEWL) measurements should be adapted for the eyelids. Further research on eyelid microbiome and transcriptomic biomarkers in the tear fluid and/or eyelid keratinocytes is required. Atopy patch testing with house dust mites (HDMs) can be helpful in selected cases but needs further standardization. Machine learning algorithms may aid image analysis for automated patch test readings and may leverage transcriptomic data for diagnostic classifications, particularly in ambiguous cases, and treatment monitoring in ED.</div></div><div><h3>Conclusions and relevance</h3><div>ED diagnosis can be challenging and may require the collaboration of ophthalmologists, dermatologists, allergists, and rheumatologists. Diagnostic innovations exist but their value in the diagnostic work-up is currently unclear.</div></div>","PeriodicalId":21159,"journal":{"name":"Progress in Retinal and Eye Research","volume":"109 ","pages":"Article 101399"},"PeriodicalIF":14.7,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145125955","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 : 2025-11-01Epub Date: 2025-11-14DOI: 10.1016/j.preteyeres.2025.101415
Chen-Wei Pan , Xing-Xuan Dong , Carla Lanca , Yining Wang , Seang-Mei Saw , Xiangui He , Dan-Ning Hu , Qiao Fan , Andrzej Grzybowski , Kyoko Ohno-Matsui
The global prevalence of myopia and pathologic myopia (PM) has dramatically increased, raising significant public health concerns due to associated vision-threatening complications, such as myopic maculopathy (MM). This comprehensive review integrates the latest evidence regarding the environmental, genetic, and epigenetic factors contributing to myopia, as well as recent advances in precision medicine and therapeutic approaches aimed at mitigating the disease's impact. We examine how environmental factors interact with polygenic risk factors and epigenetic changes to influence disease progression. The application of artificial intelligence (AI) enhances the integration of genomic, environmental, and clinical data, thereby improving risk assessment and personalizing treatment options. Therapeutic strategies, including the use of low-dose atropine, orthokeratology, and repeated low-level red-light therapy, have shown promise in controlling myopia. Furthermore, emerging gene-editing techniques are being developed, although they are unlikely to be implemented as treatments for myopia and PM in the near future. Despite these advancements, disparities in resource availability and the implementation of interventions continue to hinder global equity, underscoring the need for scalable solutions such as mobile health applications and community-based preventive programs. This review emphasizes the importance of interdisciplinary collaboration to merge precision medicine with public health strategies, ensuring that scientific breakthroughs are equitably translated into clinical care. By aligning environmental preventive measures, genetic discoveries, and AI-powered innovations, this review outlines a strategic plan for reducing the global burden of myopia and its complications.
{"title":"Global perspectives on myopia and pathologic myopia: From environmental drivers to precision medicine","authors":"Chen-Wei Pan , Xing-Xuan Dong , Carla Lanca , Yining Wang , Seang-Mei Saw , Xiangui He , Dan-Ning Hu , Qiao Fan , Andrzej Grzybowski , Kyoko Ohno-Matsui","doi":"10.1016/j.preteyeres.2025.101415","DOIUrl":"10.1016/j.preteyeres.2025.101415","url":null,"abstract":"<div><div>The global prevalence of myopia and pathologic myopia (PM) has dramatically increased, raising significant public health concerns due to associated vision-threatening complications, such as myopic maculopathy (MM). This comprehensive review integrates the latest evidence regarding the environmental, genetic, and epigenetic factors contributing to myopia, as well as recent advances in precision medicine and therapeutic approaches aimed at mitigating the disease's impact. We examine how environmental factors interact with polygenic risk factors and epigenetic changes to influence disease progression. The application of artificial intelligence (AI) enhances the integration of genomic, environmental, and clinical data, thereby improving risk assessment and personalizing treatment options. Therapeutic strategies, including the use of low-dose atropine, orthokeratology, and repeated low-level red-light therapy, have shown promise in controlling myopia. Furthermore, emerging gene-editing techniques are being developed, although they are unlikely to be implemented as treatments for myopia and PM in the near future. Despite these advancements, disparities in resource availability and the implementation of interventions continue to hinder global equity, underscoring the need for scalable solutions such as mobile health applications and community-based preventive programs. This review emphasizes the importance of interdisciplinary collaboration to merge precision medicine with public health strategies, ensuring that scientific breakthroughs are equitably translated into clinical care. By aligning environmental preventive measures, genetic discoveries, and AI-powered innovations, this review outlines a strategic plan for reducing the global burden of myopia and its complications.</div></div>","PeriodicalId":21159,"journal":{"name":"Progress in Retinal and Eye Research","volume":"109 ","pages":"Article 101415"},"PeriodicalIF":14.7,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145531189","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 : 2025-11-01Epub Date: 2025-09-23DOI: 10.1016/j.preteyeres.2025.101403
Debora Napoli , Beatrice Di Marco , Giulia Salamone , Noemi Orsini , Raffaele Mazziotti , Enrica Strettoi
Retinitis Pigmentosa (RP) is an incurable disorder characterized by progressive vision loss due to photoreceptor degeneration, typically following a rod-cone sequence. Rods die first, driven by primary genetic mutations; cones then degenerate secondarily through bystander mechanisms. As cones mediate daylight and high-acuity vision, crucial to human visual function, even partial preservation of these cells can profoundly enhance quality of life, regardless of the underlying genetic defect. Although significant progress has been made in understanding RP genetics and developing targeted therapies such as gene augmentation, a universal cure remains out of reach. This review centers on the biological drivers of secondary cone degeneration, with a focus on oxidative stress, metabolic dysfunction, and inflammation. Inflammation, now recognized as a key contributor to RP progression, involves the activation of microglia and infiltration by macrophages, both of which exacerbate retinal damage and offer promising therapeutic targets. We briefly survey current treatment modalities that have advanced to clinical application, including gene therapies, retinal prostheses, and neuroprotective strategies. Building on this therapeutic landscape, we propose a rationale for exploring ocular glucocorticoids—specifically dexamethasone—as a treatment avenue. Recent in vivo evidence from the rd10 mouse model demonstrates that intraocular dexamethasone, a long-approved agent for ocular inflammation, can preserve cone photoreceptors and protect the retinal pigment epithelium, a critical barrier for retinal homeostasis.
Glucocorticoids may thus represent a class of mutation-agnostic therapeutics with strong translational promise. Their repurposing for RP could help safeguard photoreceptors and visual function, addressing a pressing and unmet clinical need.
{"title":"Keeping the lights on: a new role for an old drug to support cone survival in Retinitis Pigmentosa","authors":"Debora Napoli , Beatrice Di Marco , Giulia Salamone , Noemi Orsini , Raffaele Mazziotti , Enrica Strettoi","doi":"10.1016/j.preteyeres.2025.101403","DOIUrl":"10.1016/j.preteyeres.2025.101403","url":null,"abstract":"<div><div>Retinitis Pigmentosa (RP) is an incurable disorder characterized by progressive vision loss due to photoreceptor degeneration, typically following a rod-cone sequence. Rods die first, driven by primary genetic mutations; cones then degenerate secondarily through bystander mechanisms. As cones mediate daylight and high-acuity vision, crucial to human visual function, even partial preservation of these cells can profoundly enhance quality of life, regardless of the underlying genetic defect. Although significant progress has been made in understanding RP genetics and developing targeted therapies such as gene augmentation, a universal cure remains out of reach. This review centers on the biological drivers of secondary cone degeneration, with a focus on oxidative stress, metabolic dysfunction, and inflammation. Inflammation, now recognized as a key contributor to RP progression, involves the activation of microglia and infiltration by macrophages, both of which exacerbate retinal damage and offer promising therapeutic targets. We briefly survey current treatment modalities that have advanced to clinical application, including gene therapies, retinal prostheses, and neuroprotective strategies. Building on this therapeutic landscape, we propose a rationale for exploring ocular glucocorticoids—specifically dexamethasone—as a treatment avenue. Recent in vivo evidence from the rd10 mouse model demonstrates that intraocular dexamethasone, a long-approved agent for ocular inflammation, can preserve cone photoreceptors and protect the retinal pigment epithelium, a critical barrier for retinal homeostasis.</div><div>Glucocorticoids may thus represent a class of mutation-agnostic therapeutics with strong translational promise. Their repurposing for RP could help safeguard photoreceptors and visual function, addressing a pressing and unmet clinical need.</div></div>","PeriodicalId":21159,"journal":{"name":"Progress in Retinal and Eye Research","volume":"109 ","pages":"Article 101403"},"PeriodicalIF":14.7,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145150636","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 : 2025-11-01Epub Date: 2025-09-20DOI: 10.1016/j.preteyeres.2025.101402
Jost B. Jonas , Rahul A. Jonas , Songhomitra Panda-Jonas
Axial myopia is characterized by a panoply of morphological, clinical and histological, features in association with longer axial length. It includes changes in the region peripheral to the optic nerve head (reduction in the density of photoreceptors and retinal pigment epithelium (RPE) cells and retinal thinning); in the optic nerve head region in moderately myopic eyes (shift of Bruch's membrane (BM) opening typically in the temporal/inferior direction, leading to a secondary BM overhang into the nasal intrapapillary compartment, BM absence in the temporal parapapillary region (“gamma zone”), and optic disc ovalization due to shortening of the ophthalmoscopically visible horizontal disc diameter; and widening of the RPE opening leading to myopic parapapillary beta zone), and in highly myopic eyes (BM opening enlargement resulting in a circular gamma zone, elongation and thinning of the lamina cribrosa (“secondary macrodisc”) and of the peripapillary scleral flange (“parapapillary delta zone”); and in the macular region with an elongation of the fovea–optic disc distance, reduction in angle kappa, straightening/stretching of the papillomacular retinal blood vessels and retinal nerve fibers (leading to a re-arrangement of the retinal nerve fibers with a myopia-specific regional distribution of the retinal nerve fiber layer thickness profile), choroidal thinning most pronounced at the posterior pole and affecting mainly the medium-sized and large choroidal vessel layer), and scleral thinning. Pathologic changes in the macular region are extrafoveally located, linear RPE layer defects (lacquer cracks), potentially widening to round RPE layer defects (patchy atrophies), in some eyes with central BM defects; BM defects with RPE layer defects in the foveal region, accompanied by macular neovascularization or subsequent subretinal RPE cell proliferation (“macular atrophy”); myopic macular retinoschisis; and staphylomas. With longer axial length, the prevalence of non-glaucomatous optic neuropathy and glaucoma-like/glaucomatous optic neuropathy steeply increases beyond an axial length of 26.0–26.5 mm. With BM thickness being independent of axial length and in view of eye shape change from an oblate or sphere in emmetropia to a prolate rotational ellipsoid in myopia, the myopia specific morphological changes may be associated with a primary BM enlargement in the region peripheral to the optic disc.
{"title":"Clinical and histological aspects of the anatomy of myopia, myopic macular degeneration and myopia-associated optic neuropathy","authors":"Jost B. Jonas , Rahul A. Jonas , Songhomitra Panda-Jonas","doi":"10.1016/j.preteyeres.2025.101402","DOIUrl":"10.1016/j.preteyeres.2025.101402","url":null,"abstract":"<div><div>Axial myopia is characterized by a panoply of morphological, clinical and histological, features in association with longer axial length. It includes changes in the region peripheral to the optic nerve head (reduction in the density of photoreceptors and retinal pigment epithelium (RPE) cells and retinal thinning); in the optic nerve head region in moderately myopic eyes (shift of Bruch's membrane (BM) opening typically in the temporal/inferior direction, leading to a secondary BM overhang into the nasal intrapapillary compartment, BM absence in the temporal parapapillary region (“gamma zone”), and optic disc ovalization due to shortening of the ophthalmoscopically visible horizontal disc diameter; and widening of the RPE opening leading to myopic parapapillary beta zone), and in highly myopic eyes (BM opening enlargement resulting in a circular gamma zone, elongation and thinning of the lamina cribrosa (“secondary macrodisc”) and of the peripapillary scleral flange (“parapapillary delta zone”); and in the macular region with an elongation of the fovea–optic disc distance, reduction in angle kappa, straightening/stretching of the papillomacular retinal blood vessels and retinal nerve fibers (leading to a re-arrangement of the retinal nerve fibers with a myopia-specific regional distribution of the retinal nerve fiber layer thickness profile), choroidal thinning most pronounced at the posterior pole and affecting mainly the medium-sized and large choroidal vessel layer), and scleral thinning. Pathologic changes in the macular region are extrafoveally located, linear RPE layer defects (lacquer cracks), potentially widening to round RPE layer defects (patchy atrophies), in some eyes with central BM defects; BM defects with RPE layer defects in the foveal region, accompanied by macular neovascularization or subsequent subretinal RPE cell proliferation (“macular atrophy”); myopic macular retinoschisis; and staphylomas. With longer axial length, the prevalence of non-glaucomatous optic neuropathy and glaucoma-like/glaucomatous optic neuropathy steeply increases beyond an axial length of 26.0–26.5 mm. With BM thickness being independent of axial length and in view of eye shape change from an oblate or sphere in emmetropia to a prolate rotational ellipsoid in myopia, the myopia specific morphological changes may be associated with a primary BM enlargement in the region peripheral to the optic disc.</div></div>","PeriodicalId":21159,"journal":{"name":"Progress in Retinal and Eye Research","volume":"109 ","pages":"Article 101402"},"PeriodicalIF":14.7,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145125901","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}
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