Pub Date : 2025-09-19DOI: 10.1016/j.preteyeres.2025.101404
Brian S. McKay , Andreas M. Grabrucker , Richard B. Thompson , Emily Y. Chew , Imre Lengyel , Héctor González-Iglesias
Zinc is an essential trace mineral that plays a crucial role in numerous bodily functions, including immune response, wound healing, and protein synthesis. Regarding eye health, zinc is particularly important due to its high concentration, functional abundance, and critical roles in the retina/RPE/choroid complex, where both deficiency and excess can lead to cellular dysfunction. This mineral contributes significantly to the maintenance of the structure and function of the tissues, and it is believed to help protect against oxidative stress, which can damage cells in the eye. The retinal pigment epithelium/choroid complex (RPE/choroid) contains the highest zinc concentration. Therefore, it is unsurprising that several eye disorders associated with this interface are associated with reduced zinc accumulation, and zinc supplementation has become an essential secondary preventive therapy for diseases like age-related macular degeneration (AMD). Despite zinc's importance in health and diseases of the outer retina, it still needs to be fully understood how zinc participates in cellular and molecular events and how zinc supplementation might be beneficial. However, it appears that adequate zinc levels are essential for retinal health and overall vision, particularly as we age. This review is focused on summarising our current understanding of the biology of zinc, with particular attention paid to the RPE/choroid interface.
{"title":"Zinc in eye health, retinal biology and disease","authors":"Brian S. McKay , Andreas M. Grabrucker , Richard B. Thompson , Emily Y. Chew , Imre Lengyel , Héctor González-Iglesias","doi":"10.1016/j.preteyeres.2025.101404","DOIUrl":"10.1016/j.preteyeres.2025.101404","url":null,"abstract":"<div><div>Zinc is an essential trace mineral that plays a crucial role in numerous bodily functions, including immune response, wound healing, and protein synthesis. Regarding eye health, zinc is particularly important due to its high concentration, functional abundance, and critical roles in the retina/RPE/choroid complex, where both deficiency and excess can lead to cellular dysfunction. This mineral contributes significantly to the maintenance of the structure and function of the tissues, and it is believed to help protect against oxidative stress, which can damage cells in the eye. The retinal pigment epithelium/choroid complex (RPE/choroid) contains the highest zinc concentration. Therefore, it is unsurprising that several eye disorders associated with this interface are associated with reduced zinc accumulation, and zinc supplementation has become an essential secondary preventive therapy for diseases like age-related macular degeneration (AMD). Despite zinc's importance in health and diseases of the outer retina, it still needs to be fully understood how zinc participates in cellular and molecular events and how zinc supplementation might be beneficial. However, it appears that adequate zinc levels are essential for retinal health and overall vision, particularly as we age. This review is focused on summarising our current understanding of the biology of zinc, with particular attention paid to the RPE/choroid interface.</div></div>","PeriodicalId":21159,"journal":{"name":"Progress in Retinal and Eye Research","volume":"109 ","pages":"Article 101404"},"PeriodicalIF":14.7,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145113590","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 : 2025-09-15DOI: 10.1016/j.preteyeres.2025.101400
Brian P. Hall , Sakshi Shiromani , Brian L. Vanderbeek , Sayantan Datta , Preston E. Girardot , Archeta Rajagopalan , John M. Nickerson , Jeffrey H. Boatright , Nieraj Jain
Pentosan polysulfate (PPS) maculopathy is a progressive, vision-threatening retinal disorder linked to prolonged use of PPS, a heparin-like sulfated polysaccharide prescribed for interstitial cystitis/bladder pain syndrome. Affected individuals often experience impaired dark adaptation and progressive central vision loss. Fundus imaging commonly reveals hyperpigmented macular clumps at the level of the retinal pigment epithelium (RPE), and a distinctive pattern of autofluorescence abnormality in the posterior fundus. This degenerative maculopathy may continue to progress even after drug cessation, with some patients developing macular atrophy years later.
While the underlying pathogenic mechanism remains unclear, mounting evidence supports a causal relationship between PPS use and the macular pathology. Studies have repeatedly demonstrated the strength of the association; the dose-response relationship; and the lack of confounding by indication. Furthermore, laboratory studies demonstrate that such a toxicity is biologically plausible, suggesting a direct toxicity to the RPE and/or choroid.
Given the widespread use of PPS over many decades, tens of thousands of individuals are already at risk for toxicity, with no known treatment available. However, screening rates remain low; prescribing rates continue to rise in certain regions; and novel applications for the drug, such as subcutaneous injection for osteoarthritis, are under clinical investigation. Consequently, there is a pressing need for increased recognition of PPS toxicity and further understanding of disease mechanisms. This review summarizes the clinical characteristics of PPS maculopathy, evaluates its public health impact, explores potential pathogenic mechanisms, and presents a compelling case for causality using clinical, laboratory, and epidemiological evidence.
{"title":"Pentosan polysulfate maculopathy: clinical considerations, pathobiology, and causality","authors":"Brian P. Hall , Sakshi Shiromani , Brian L. Vanderbeek , Sayantan Datta , Preston E. Girardot , Archeta Rajagopalan , John M. Nickerson , Jeffrey H. Boatright , Nieraj Jain","doi":"10.1016/j.preteyeres.2025.101400","DOIUrl":"10.1016/j.preteyeres.2025.101400","url":null,"abstract":"<div><div>Pentosan polysulfate (PPS) maculopathy is a progressive, vision-threatening retinal disorder linked to prolonged use of PPS, a heparin-like sulfated polysaccharide prescribed for interstitial cystitis/bladder pain syndrome. Affected individuals often experience impaired dark adaptation and progressive central vision loss. Fundus imaging commonly reveals hyperpigmented macular clumps at the level of the retinal pigment epithelium (RPE), and a distinctive pattern of autofluorescence abnormality in the posterior fundus. This degenerative maculopathy may continue to progress even after drug cessation, with some patients developing macular atrophy years later.</div><div>While the underlying pathogenic mechanism remains unclear, mounting evidence supports a causal relationship between PPS use and the macular pathology. Studies have repeatedly demonstrated the strength of the association; the dose-response relationship; and the lack of confounding by indication. Furthermore, laboratory studies demonstrate that such a toxicity is biologically plausible, suggesting a direct toxicity to the RPE and/or choroid.</div><div>Given the widespread use of PPS over many decades, tens of thousands of individuals are already at risk for toxicity, with no known treatment available. However, screening rates remain low; prescribing rates continue to rise in certain regions; and novel applications for the drug, such as subcutaneous injection for osteoarthritis, are under clinical investigation. Consequently, there is a pressing need for increased recognition of PPS toxicity and further understanding of disease mechanisms. This review summarizes the clinical characteristics of PPS maculopathy, evaluates its public health impact, explores potential pathogenic mechanisms, and presents a compelling case for causality using clinical, laboratory, and epidemiological evidence.</div></div>","PeriodicalId":21159,"journal":{"name":"Progress in Retinal and Eye Research","volume":"109 ","pages":"Article 101400"},"PeriodicalIF":14.7,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145081424","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 : 2025-08-20DOI: 10.1016/j.preteyeres.2025.101392
Olaf Dammann, Tora S. Morken, Steven E. Brooks, Alison Chu, Christiane E.L. Dammann, M. Elizabeth Hartnett, Brian K. Stansfield, David K. Wallace
We hypothesize that the major pathologies associated with the visual system in preterm infants, retinopathy of prematurity (ROP), cerebral visual impairment (CVI), and neurodevelopmental impairment (NDI), are unified by a common etio-pathogenesis involving intermittent and/or sustained systemic inflammation (ISSI). We refer to the resulting adverse visual outcomes (AVO) as “visuopathy of prematurity” (VOP). We present the published evidence supporting an etio-pathogenic paradigm centered around ISSI that begins before birth (early phase 1), is exacerbated in the newborn period (intermediate phase 2), and culminates in adverse visual and neurodevelopmental outcomes (late phase 3).
{"title":"Elements of visuopathy of prematurity are unified by intermittent or sustained systemic inflammation","authors":"Olaf Dammann, Tora S. Morken, Steven E. Brooks, Alison Chu, Christiane E.L. Dammann, M. Elizabeth Hartnett, Brian K. Stansfield, David K. Wallace","doi":"10.1016/j.preteyeres.2025.101392","DOIUrl":"10.1016/j.preteyeres.2025.101392","url":null,"abstract":"<div><div>We hypothesize that the major pathologies associated with the visual system in preterm infants, retinopathy of prematurity (ROP), cerebral visual impairment (CVI), and neurodevelopmental impairment (NDI), are unified by a common etio-pathogenesis involving intermittent and/or sustained systemic inflammation (ISSI). We refer to the resulting adverse visual outcomes (AVO) as “visuopathy of prematurity” (VOP). We present the published evidence supporting an etio-pathogenic paradigm centered around ISSI that begins before birth (early phase 1), is exacerbated in the newborn period (intermediate phase 2), and culminates in adverse visual and neurodevelopmental outcomes (late phase 3).</div></div>","PeriodicalId":21159,"journal":{"name":"Progress in Retinal and Eye Research","volume":"109 ","pages":"Article 101392"},"PeriodicalIF":14.7,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144899258","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 : 2025-08-15DOI: 10.1016/j.preteyeres.2025.101391
João Pedro Marques , Inês Santos Sousa , Daniela Patrício , Bruno F. Simões , Oluji Chukwunalu , Christina Zeitz , Isabelle Audo , Rob W.J. Collin , Peter M.J. Quinn , António Francisco Ambrósio , C. Henrique Alves
Eyes shut homologue (EYS) stands out as one of the most commonly mutated genes causing autosomal recessive retinitis pigmentosa (arRP), with a worldwide prevalence ranging from 1.2 % to 23.5 %. The EYS gene is predominantly expressed in retinal photoreceptor cells, where four transcripts have been identified, each varying in length. The human EYS protein initiates with a signal peptide and comprises 21 epidermal growth factor (EGF)-like domains in its N-terminal followed by five C-terminal LamG domains, interspersed among additional EGF repeats. The existence of different isoforms suggests potential variations in their functions within the human body.
EYS-associated retinopathies present with a severe clinical phenotype and currently have no treatment options. The limited understanding of the role of EYS in the healthy and diseased retina remains a significant barrier to translating current advances into viable therapeutic interventions. This review consolidates existing knowledge on the molecular characteristics of EYS, animal and disease models, the clinical impact of EYS disease-causing variants, and the potential of emerging technologies in future therapeutic strategies for EYS-related diseases. Additionally, we contribute to the field by further elucidating the localization of EYS in the human retina, analyzing the most frequent variants and their positions within the gene, and proposing antisense oligonucleotides, and Prime and Base Editing strategies to correct some of the most recurrent pathogenic variants in EYS.
{"title":"Eyes shut homolog (EYS): Connecting molecule to disease","authors":"João Pedro Marques , Inês Santos Sousa , Daniela Patrício , Bruno F. Simões , Oluji Chukwunalu , Christina Zeitz , Isabelle Audo , Rob W.J. Collin , Peter M.J. Quinn , António Francisco Ambrósio , C. Henrique Alves","doi":"10.1016/j.preteyeres.2025.101391","DOIUrl":"10.1016/j.preteyeres.2025.101391","url":null,"abstract":"<div><div>Eyes shut homologue (<em>EYS)</em> stands out as one of the most commonly mutated genes causing autosomal recessive retinitis pigmentosa (arRP), with a worldwide prevalence ranging from 1.2 % to 23.5 %. The <em>EYS</em> gene is predominantly expressed in retinal photoreceptor cells, where four transcripts have been identified, each varying in length. The human EYS protein initiates with a signal peptide and comprises 21 epidermal growth factor (EGF)-like domains in its N-terminal followed by five C-terminal LamG domains, interspersed among additional EGF repeats. The existence of different isoforms suggests potential variations in their functions within the human body.</div><div>EYS-associated retinopathies present with a severe clinical phenotype and currently have no treatment options. The limited understanding of the role of EYS in the healthy and diseased retina remains a significant barrier to translating current advances into viable therapeutic interventions. This review consolidates existing knowledge on the molecular characteristics of EYS, animal and disease models, the clinical impact of <em>EYS</em> disease-causing variants, and the potential of emerging technologies in future therapeutic strategies for <em>EYS</em>-related diseases. Additionally, we contribute to the field by further elucidating the localization of EYS in the human retina, analyzing the most frequent variants and their positions within the gene, and proposing antisense oligonucleotides, and Prime and Base Editing strategies to correct some of the most recurrent pathogenic variants in <em>EYS</em>.</div></div>","PeriodicalId":21159,"journal":{"name":"Progress in Retinal and Eye Research","volume":"108 ","pages":"Article 101391"},"PeriodicalIF":14.7,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144874951","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 : 2025-07-14DOI: 10.1016/j.preteyeres.2025.101390
Hanaa Ghanawi, Susanne F. Koch
Retinitis pigmentosa (RP) is a group of hereditary retinal diseases that lead to progressive vision loss, with most disease-causing genes expressed in rod photoreceptors and a smaller fraction in retinal pigment epithelium (RPE) cells. The RPE and photoreceptor cells share a symbiotic relationship characterized by close spatial and functional interactions that play a pivotal role in vision. Although the role of RPE is fundamental to the retina, its involvement in retinal pathogenesis, and, in particular, in RP remains underappreciated. In this review, we summarize morphological alterations in the RPE resulting from pathogenic mutations specific to RPE cells, as well as those occurring secondary to photoreceptor degeneration. We provide a comprehensive summary of how mutations in RPE-specific genes play a key role in the pathophysiology of RP. Finally, we discuss the latest therapeutic approaches, including AAV-mediated gene augmentation, RPE cell transplantation, and pharmacological interventions.
{"title":"The versatile roles of retinal pigment epithelium in the pathophysiology of retinitis pigmentosa","authors":"Hanaa Ghanawi, Susanne F. Koch","doi":"10.1016/j.preteyeres.2025.101390","DOIUrl":"10.1016/j.preteyeres.2025.101390","url":null,"abstract":"<div><div>Retinitis pigmentosa (RP) is a group of hereditary retinal diseases that lead to progressive vision loss, with most disease-causing genes expressed in rod photoreceptors and a smaller fraction in retinal pigment epithelium (RPE) cells. The RPE and photoreceptor cells share a symbiotic relationship characterized by close spatial and functional interactions that play a pivotal role in vision. Although the role of RPE is fundamental to the retina, its involvement in retinal pathogenesis, and, in particular, in RP remains underappreciated. In this review, we summarize morphological alterations in the RPE resulting from pathogenic mutations specific to RPE cells, as well as those occurring secondary to photoreceptor degeneration. We provide a comprehensive summary of how mutations in RPE-specific genes play a key role in the pathophysiology of RP. Finally, we discuss the latest therapeutic approaches, including AAV-mediated gene augmentation, RPE cell transplantation, and pharmacological interventions.</div></div>","PeriodicalId":21159,"journal":{"name":"Progress in Retinal and Eye Research","volume":"108 ","pages":"Article 101390"},"PeriodicalIF":18.6,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144650226","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 : 2025-07-09DOI: 10.1016/j.preteyeres.2025.101389
André Schulz , Meghal Keskar , Katelyn E. Swindle-Reilly , Valentin Junge , Bhav Harshad Parikh , Xinyi Su , Zengping Liu , Ivan Seah
During vitreoretinal surgery, the vitreous body is removed and requires a suitable replacement to ensure ocular homeostasis, as the native vitreous does not regenerate. An ideal vitreous substitute should mimic the optical, mechanical, and biochemical properties of the natural vitreous while maintaining long-term biocompatibility. Currently, clinically used substitutes such as gases and silicone oils facilitate retinal reattachment but deviate significantly from the native vitreous, leading to complications such as cataract formation, increased intraocular pressure, and emulsification. Given these limitations, there is a growing interest in hydrogels as potential vitreous substitutes due to their similarity to the native vitreous. This review therefore aspires to provide a comprehensive and detailed overview of current knowledge on the structural and biochemical composition of the vitreous, the challenges associated with existing substitutes, and recent advancements in vitreous replacement technologies. Particular attention is given to preformed and in-situ forming hydrogels, based on biopolymers and synthetic polymers, discussing their chemical composition, diverse characteristics with regard to the multiple requirements for vitreous substitutes, and clinical applicability. Finally, future challenges and opportunities in developing an ideal vitreous substitute are highlighted, including vitreous substitutes as drug delivery systems as well as cellularized vitreous substitutes by combining advanced hydrogel systems with hyalocytes as vitreous cells to further replicate the versatile characteristics and functions of the native vitreous.
{"title":"Replacing the vitreous body with hydrogels: Rationale and strategies","authors":"André Schulz , Meghal Keskar , Katelyn E. Swindle-Reilly , Valentin Junge , Bhav Harshad Parikh , Xinyi Su , Zengping Liu , Ivan Seah","doi":"10.1016/j.preteyeres.2025.101389","DOIUrl":"10.1016/j.preteyeres.2025.101389","url":null,"abstract":"<div><div>During vitreoretinal surgery, the vitreous body is removed and requires a suitable replacement to ensure ocular homeostasis, as the native vitreous does not regenerate. An ideal vitreous substitute should mimic the optical, mechanical, and biochemical properties of the natural vitreous while maintaining long-term biocompatibility. Currently, clinically used substitutes such as gases and silicone oils facilitate retinal reattachment but deviate significantly from the native vitreous, leading to complications such as cataract formation, increased intraocular pressure, and emulsification. Given these limitations, there is a growing interest in hydrogels as potential vitreous substitutes due to their similarity to the native vitreous. This review therefore aspires to provide a comprehensive and detailed overview of current knowledge on the structural and biochemical composition of the vitreous, the challenges associated with existing substitutes, and recent advancements in vitreous replacement technologies. Particular attention is given to preformed and <em>in-situ</em> forming hydrogels, based on biopolymers and synthetic polymers, discussing their chemical composition, diverse characteristics with regard to the multiple requirements for vitreous substitutes, and clinical applicability. Finally, future challenges and opportunities in developing an ideal vitreous substitute are highlighted, including vitreous substitutes as drug delivery systems as well as cellularized vitreous substitutes by combining advanced hydrogel systems with hyalocytes as vitreous cells to further replicate the versatile characteristics and functions of the native vitreous.</div></div>","PeriodicalId":21159,"journal":{"name":"Progress in Retinal and Eye Research","volume":"108 ","pages":"Article 101389"},"PeriodicalIF":18.6,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144613298","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 : 2025-07-08DOI: 10.1016/j.preteyeres.2025.101388
Janet R. Sparrow , Hye Jin Kim
Retinal pigment epithelium emits an inherent autofluorescence that originates from naturally occurring fluorophores when excited by short-wavelength light (SW-AF) in the spectral range between 400 and 590 nm. Peak excitation is 490 nm. The autofluorescence emission occurs at wavelengths between 520 and 800 nm with a peak of approximately 600 nm. For clinical purposes this emission is recorded as fundus autofluorescence either using a confocal scanning laser ophthalmoscope (cSLO; 488 nm excitation); a modified fundus camera or by ultra-wide-field ophthalmoscopic technology. The topographic distribution and intensities of fundus autofluorescence are modulated by superior-inferior differences in retinal illuminance. The autofluorescence distribution also departs from normal in the presence of retinal disease; accordingly these changing patterns assist in the diagnosis and monitoring of the disorders. The cellular source of SW-AF is consistent with an origin from a group of di-retinaldehyde (bisretinoid fluorophores) compounds that are produced randomly in photoreceptor cells and constitute the lipofuscin of the retinal pigment epithelium. Bisretinoids also contribute to retinal disease processes. Here we will primarily address this family of bisretinoid fluorophores since they account for the spectral, age- and disease-related properties of retina lipofuscin and SW-AF. Moreover, the differing absorbances exhibited by the members of this group of fluorophores accounts for the range of excitation wavelengths that elicit fluorescence emission from RPE lipofuscin and from the fundus. That range is consistent with emission from a family of fluorophores, not a single fluorophore.
{"title":"Bisretinoid lipofuscin, fundus autofluorescence and retinal disease","authors":"Janet R. Sparrow , Hye Jin Kim","doi":"10.1016/j.preteyeres.2025.101388","DOIUrl":"10.1016/j.preteyeres.2025.101388","url":null,"abstract":"<div><div>Retinal pigment epithelium emits an inherent autofluorescence that originates from naturally occurring fluorophores when excited by short-wavelength light (SW-AF) in the spectral range between 400 and 590 nm. Peak excitation is 490 nm. The autofluorescence emission occurs at wavelengths between 520 and 800 nm with a peak of approximately 600 nm. For clinical purposes this emission is recorded as fundus autofluorescence either using a confocal scanning laser ophthalmoscope (cSLO; 488 nm excitation); a modified fundus camera or by ultra-wide-field ophthalmoscopic technology. The topographic distribution and intensities of fundus autofluorescence are modulated by superior-inferior differences in retinal illuminance. The autofluorescence distribution also departs from normal in the presence of retinal disease; accordingly these changing patterns assist in the diagnosis and monitoring of the disorders. The cellular source of SW-AF is consistent with an origin from a group of di-retinaldehyde (bisretinoid fluorophores) compounds that are produced randomly in photoreceptor cells and constitute the lipofuscin of the retinal pigment epithelium. Bisretinoids also contribute to retinal disease processes. Here we will primarily address this family of bisretinoid fluorophores since they account for the spectral, age- and disease-related properties of retina lipofuscin and SW-AF. Moreover, the differing absorbances exhibited by the members of this group of fluorophores accounts for the range of excitation wavelengths that elicit fluorescence emission from RPE lipofuscin and from the fundus. That range is consistent with emission from a family of fluorophores, not a single fluorophore.</div></div>","PeriodicalId":21159,"journal":{"name":"Progress in Retinal and Eye Research","volume":"108 ","pages":"Article 101388"},"PeriodicalIF":18.6,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144604931","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 : 2025-07-05DOI: 10.1016/j.preteyeres.2025.101387
You Wang , Xinyu Liu , Wenjia Yan , Yizhe Cheng , Aohan Hou , Linyan Zhang , Jinglin Lu , Miner Yuan , Yanting Lai , Zhenglin Yang , Xiaoxin Li , Xiaoyan Ding
Familial exudative vitreoretinopathy (FEVR) is a genetically complex retinal vascular disorder, often manifesting in infancy or early childhood, and characterized by peripheral retinal avascularity, neovascularization, and retinal detachment. The disease, predominantly inherited in an autosomal dominant manner, is associated with mutations in genes such as LRP5, FZD4, and TSPAN12, which disrupt the Wnt/β-catenin and Norrin signaling pathways, critical for retinal vascular development. FEVR's clinical spectrum ranges from asymptomatic cases to severe vision loss, making early diagnosis and intervention essential for preserving sight. Management strategies include laser photocoagulation, anti-VEGF therapy, and surgery, tailored to disease stage and patient age. The future of FEVR treatment lies in predictive genetics, early screening, and proactive therapy. Ongoing research into the molecular mechanisms of FEVR offers the potential for transforming this progressive disease into a preventable one, improving outcomes for affected individuals.
{"title":"Phenotyping and genotyping FEVR: Molecular genetics, clinical and imaging features, and therapeutics","authors":"You Wang , Xinyu Liu , Wenjia Yan , Yizhe Cheng , Aohan Hou , Linyan Zhang , Jinglin Lu , Miner Yuan , Yanting Lai , Zhenglin Yang , Xiaoxin Li , Xiaoyan Ding","doi":"10.1016/j.preteyeres.2025.101387","DOIUrl":"10.1016/j.preteyeres.2025.101387","url":null,"abstract":"<div><div>Familial exudative vitreoretinopathy (FEVR) is a genetically complex retinal vascular disorder, often manifesting in infancy or early childhood, and characterized by peripheral retinal avascularity, neovascularization, and retinal detachment. The disease, predominantly inherited in an autosomal dominant manner, is associated with mutations in genes such as <em>LRP5, FZD4,</em> and <em>TSPAN12</em>, which disrupt the Wnt/β-catenin and Norrin signaling pathways, critical for retinal vascular development. FEVR's clinical spectrum ranges from asymptomatic cases to severe vision loss, making early diagnosis and intervention essential for preserving sight. Management strategies include laser photocoagulation, anti-VEGF therapy, and surgery, tailored to disease stage and patient age. The future of FEVR treatment lies in predictive genetics, early screening, and proactive therapy. Ongoing research into the molecular mechanisms of FEVR offers the potential for transforming this progressive disease into a preventable one, improving outcomes for affected individuals.</div></div>","PeriodicalId":21159,"journal":{"name":"Progress in Retinal and Eye Research","volume":"108 ","pages":"Article 101387"},"PeriodicalIF":18.6,"publicationDate":"2025-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144584706","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 : 2025-07-01DOI: 10.1016/j.preteyeres.2025.101364
Michael Stopfer , Ingrid Zahn , Katharina Jüngert , Gerhard Aumüller , Frans L. Moll , Martin Schicht , Helen P. Makarenkova , Cintia S. de Paiva , Friedrich P. Paulsen
{"title":"Corrigendum to “Glands of Moll: history, current knowledge and their role in ocular surface homeostasis and disease” [Progr. Retin. Eye Res. 106 (2025) 101362]","authors":"Michael Stopfer , Ingrid Zahn , Katharina Jüngert , Gerhard Aumüller , Frans L. Moll , Martin Schicht , Helen P. Makarenkova , Cintia S. de Paiva , Friedrich P. Paulsen","doi":"10.1016/j.preteyeres.2025.101364","DOIUrl":"10.1016/j.preteyeres.2025.101364","url":null,"abstract":"","PeriodicalId":21159,"journal":{"name":"Progress in Retinal and Eye Research","volume":"107 ","pages":"Article 101364"},"PeriodicalIF":18.6,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144120661","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-06-21DOI: 10.1016/j.preteyeres.2025.101380
Rupesh Agrawal , Yun Yao Goh , William Rojas-Carabali , Carlos Cifuentes-González , Sanjay Srinivasan , Bernard Yu-Hor Thong , Alejandra de-la-Torre , Cesar Michael Samson , Jyotirmay Biswas , Robert Patrick Finger , John H. Kempen
Non-infectious uveitis (NIU) is a potentially sight-threatening intraocular inflammatory condition that may arise idiopathically or in association with systemic immune-mediated diseases. While corticosteroids remain essential for rapid suppression of inflammation, their long-term use is limited by significant systemic and ocular side effects. Thus, immunomodulatory therapy (IMT)—including antimetabolites, calcineurin inhibitors, biologics, and emerging small molecules—has become central to achieving sustained control with a reduced corticosteroid burden in chronic cases.
Despite a range of therapeutic options, significant challenges persist. Safe, remission-inducing treatments remain elusive; tapering strategies are poorly standardized; and evidence for optimal combinations or long-term outcomes remains limited. Recent registries, such as Programme for Ocular Inflammation and Infection Translational Research (PROTON) and Treatment Exit Options for Uveitis (TOFU), are beginning to address the unmet need for structured treatment exit frameworks. Moreover, advances in imaging and artificial intelligence may soon enable real-time monitoring of disease status and risk stratification, although the development of large, well-annotated cohorts to be subject to such analysis remains a key hurdle.
This review summarizes the current role of IMT in the management of NIU, with an emphasis on corticosteroid-sparing strategies. We highlight the use of conventional immunosuppressants—including antimetabolites, calcineurin inhibitors, and alkylating agents—as well as newer biologic, smallmolecule, and interferon-based therapies. We outline where IMT fits within the broader treatment algorithm, discuss emerging evidence for earlier initiation, and explore future directions in targeted and personalized immunotherapy. We also explore future directions, including personalized approaches, biomarker-driven therapy, and the promise of AI-guided prediction models.
{"title":"Immunomodulatory therapy in non-infectious Uveitis: Current landscape, gaps, and future directions","authors":"Rupesh Agrawal , Yun Yao Goh , William Rojas-Carabali , Carlos Cifuentes-González , Sanjay Srinivasan , Bernard Yu-Hor Thong , Alejandra de-la-Torre , Cesar Michael Samson , Jyotirmay Biswas , Robert Patrick Finger , John H. Kempen","doi":"10.1016/j.preteyeres.2025.101380","DOIUrl":"10.1016/j.preteyeres.2025.101380","url":null,"abstract":"<div><div>Non-infectious uveitis (NIU) is a potentially sight-threatening intraocular inflammatory condition that may arise idiopathically or in association with systemic immune-mediated diseases. While corticosteroids remain essential for rapid suppression of inflammation, their long-term use is limited by significant systemic and ocular side effects. Thus, immunomodulatory therapy (IMT)—including antimetabolites, calcineurin inhibitors, biologics, and emerging small molecules—has become central to achieving sustained control with a reduced corticosteroid burden in chronic cases.</div><div>Despite a range of therapeutic options, significant challenges persist. Safe, remission-inducing treatments remain elusive; tapering strategies are poorly standardized; and evidence for optimal combinations or long-term outcomes remains limited. Recent registries, such as Programme for Ocular Inflammation and Infection Translational Research (PROTON) and Treatment Exit Options for Uveitis (TOFU), are beginning to address the unmet need for structured treatment exit frameworks. Moreover, advances in imaging and artificial intelligence may soon enable real-time monitoring of disease status and risk stratification, although the development of large, well-annotated cohorts to be subject to such analysis remains a key hurdle.</div><div>This review summarizes the current role of IMT in the management of NIU, with an emphasis on corticosteroid-sparing strategies. We highlight the use of conventional immunosuppressants—including antimetabolites, calcineurin inhibitors, and alkylating agents—as well as newer biologic, smallmolecule, and interferon-based therapies. We outline where IMT fits within the broader treatment algorithm, discuss emerging evidence for earlier initiation, and explore future directions in targeted and personalized immunotherapy. We also explore future directions, including personalized approaches, biomarker-driven therapy, and the promise of AI-guided prediction models.</div></div>","PeriodicalId":21159,"journal":{"name":"Progress in Retinal and Eye Research","volume":"108 ","pages":"Article 101380"},"PeriodicalIF":18.6,"publicationDate":"2025-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144335476","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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