Pub Date : 2025-09-01Epub 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":"2025-09-01","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 : 2025-09-01Epub 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":"2025-09-01","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 : 2025-09-01Epub 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":"2025-09-01","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 : 2025-09-01Epub 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":"2025-09-01","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 : 2025-09-01Epub 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":"2025-09-01","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}
Pub Date : 2025-07-01Epub Date: 2025-06-03DOI: 10.1016/j.preteyeres.2025.101374
Maria Cristina Savastano , Clara Rizzo , Claudia Fossataro , Daniela Bacherini , Fabrizio Giansanti , Alfonso Savastano , Giovanni Arcuri , Stanislao Rizzo , Francesco Faraldi
The adoption of artificial intelligence (AI) in ophthalmology holds great promise for improving diagnostic accuracy, optimizing workflows, and enhancing patient care. However, regulatory, ethical, and technical challenges must be addressed to ensure its safe and effective implementation. Bias in AI can lead to disparities in healthcare delivery, while the “black-box problem” raises concerns about transparency and trust. Ethical principles must guide AI integration, particularly regarding patient safety, accountability, and liability. Privacy risks related to data collection and security are especially critical in ophthalmology, where large imaging datasets are essential. Additionally, AI-generated inaccuracies, or “hallucinations,” pose potential risks to clinical decision-making. Cybersecurity threats targeting AI-powered healthcare systems further emphasize the need for robust protections. Despite these challenges, AI has the potential to improve access to ophthalmic care, particularly in underserved regions, as seen in AI-assisted diabetic retinopathy screening. However, financial and infrastructural barriers remain significant obstacles to widespread adoption. Addressing these issues requires collaboration among stakeholders, including regulators, healthcare providers, AI developers, and policymakers, to establish clear guidelines and promote trustworthy AI systems. This review explores key regulatory and ethical concerns and highlights strategies to ensure the responsible integration of AI into ophthalmology.
{"title":"Artificial intelligence in ophthalmology: Progress, challenges, and ethical implications","authors":"Maria Cristina Savastano , Clara Rizzo , Claudia Fossataro , Daniela Bacherini , Fabrizio Giansanti , Alfonso Savastano , Giovanni Arcuri , Stanislao Rizzo , Francesco Faraldi","doi":"10.1016/j.preteyeres.2025.101374","DOIUrl":"10.1016/j.preteyeres.2025.101374","url":null,"abstract":"<div><div>The adoption of artificial intelligence (AI) in ophthalmology holds great promise for improving diagnostic accuracy, optimizing workflows, and enhancing patient care. However, regulatory, ethical, and technical challenges must be addressed to ensure its safe and effective implementation. Bias in AI can lead to disparities in healthcare delivery, while the “black-box problem” raises concerns about transparency and trust. Ethical principles must guide AI integration, particularly regarding patient safety, accountability, and liability. Privacy risks related to data collection and security are especially critical in ophthalmology, where large imaging datasets are essential. Additionally, AI-generated inaccuracies, or “hallucinations,” pose potential risks to clinical decision-making. Cybersecurity threats targeting AI-powered healthcare systems further emphasize the need for robust protections. Despite these challenges, AI has the potential to improve access to ophthalmic care, particularly in underserved regions, as seen in AI-assisted diabetic retinopathy screening. However, financial and infrastructural barriers remain significant obstacles to widespread adoption. Addressing these issues requires collaboration among stakeholders, including regulators, healthcare providers, AI developers, and policymakers, to establish clear guidelines and promote trustworthy AI systems. This review explores key regulatory and ethical concerns and highlights strategies to ensure the responsible integration of AI into ophthalmology.</div></div>","PeriodicalId":21159,"journal":{"name":"Progress in Retinal and Eye Research","volume":"107 ","pages":"Article 101374"},"PeriodicalIF":18.6,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144235007","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}
Inherited retinal diseases (IRDs), such as retinitis pigmentosa, are a heterogenous group of genetic eye diseases characterized by degeneration of photoreceptors. They are the leading cause of blindness in the working age population in high-income countries and are an ideal target for the expanding gene editing tool kit, including rapidly evolving CRISPR/Cas9 technology. In this review, we provide a comprehensive analysis of CRISPR/Cas9 technologies currently being explored as therapeutic interventions for IRDs. Given the challenges posed by the growing complexity and size of gene editing systems, the delivery of these therapeutics to the retina has necessitated innovative approaches. We review current delivery methods, including nanoparticles, virus-like particles and traditional viral vectors, highlighting their advantages and limitations. This review underscores the potential transformative impact of gene editing on genetic disease management, emphasising that advancements in these technologies, coupled with improved pre-clinical models, bring clinically safe and effective treatments for IRDs within view.
{"title":"Shining light on CRISPR/Cas9 therapeutics for inherited retinal diseases","authors":"A.B. Geiger , J.G. Kennedy , L.G. Staker , T.G. Wensel , R.J. Casson , P.Q. Thomas","doi":"10.1016/j.preteyeres.2025.101376","DOIUrl":"10.1016/j.preteyeres.2025.101376","url":null,"abstract":"<div><div>Inherited retinal diseases (IRDs), such as retinitis pigmentosa, are a heterogenous group of genetic eye diseases characterized by degeneration of photoreceptors. They are the leading cause of blindness in the working age population in high-income countries and are an ideal target for the expanding gene editing tool kit, including rapidly evolving CRISPR/Cas9 technology. In this review, we provide a comprehensive analysis of CRISPR/Cas9 technologies currently being explored as therapeutic interventions for IRDs. Given the challenges posed by the growing complexity and size of gene editing systems, the delivery of these therapeutics to the retina has necessitated innovative approaches. We review current delivery methods, including nanoparticles, virus-like particles and traditional viral vectors, highlighting their advantages and limitations. This review underscores the potential transformative impact of gene editing on genetic disease management, emphasising that advancements in these technologies, coupled with improved pre-clinical models, bring clinically safe and effective treatments for IRDs within view.</div></div>","PeriodicalId":21159,"journal":{"name":"Progress in Retinal and Eye Research","volume":"107 ","pages":"Article 101376"},"PeriodicalIF":18.6,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144249422","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 : 2025-07-01Epub Date: 2024-12-27DOI: 10.1016/j.preteyeres.2024.101324
Jessica S. Karuntu , Hind Almushattat , Xuan-Thanh-An Nguyen , Astrid S. Plomp , Ronald J.A. Wanders , Carel B. Hoyng , Mary J. van Schooneveld , Nicoline E. Schalij-Delfos , Marion M. Brands , Bart P. Leroy , Clara D.M. van Karnebeek , Arthur A. Bergen , Maria M. van Genderen , Camiel J.F. Boon
Retinitis pigmentosa (RP) is a progressive inherited retinal dystrophy, characterized by the degeneration of photoreceptors, presenting as a rod-cone dystrophy. Approximately 20–30% of patients with RP also exhibit extra-ocular manifestations in the context of a syndrome. This manuscript discusses the broad spectrum of syndromes associated with RP, pathogenic mechanisms, clinical manifestations, differential diagnoses, clinical management approaches, and future perspectives. Given the diverse clinical and genetic landscape of syndromic RP, the diagnosis may be challenging. However, an accurate and timely diagnosis is essential for optimal clinical management, prognostication, and potential treatment. Broadly, the syndromes associated with RP can be categorized into ciliopathies, inherited metabolic disorders, mitochondrial disorders, and miscellaneous syndromes. Among the ciliopathies associated with RP, Usher syndrome and Bardet-Biedl syndrome are the most well-known. Less common ciliopathies include Cohen syndrome, Joubert syndrome, cranioectodermal dysplasia, asphyxiating thoracic dystrophy, Mainzer-Saldino syndrome, and RHYNS syndrome.
Several inherited metabolic disorders can present with RP, including Zellweger spectrum disorders, adult Refsum disease, α-methylacyl-CoA racemase deficiency, certain mucopolysaccharidoses, ataxia with vitamin E deficiency, abetalipoproteinemia, several neuronal ceroid lipofuscinoses, mevalonic aciduria, PKAN/HARP syndrome, PHARC syndrome, and methylmalonic acidaemia with homocystinuria type cobalamin (cbl) C disease.
Due to the mitochondria's essential role in supplying continuous energy to the retina, disruption of mitochondrial function can lead to RP, as seen in Kearns-Sayre syndrome, NARP syndrome, primary coenzyme Q10 deficiency, SSBP1-associated disease, and long chain 3-hydroxyacyl-CoA dehydrogenase deficiency. Lastly, Cockayne syndrome and PERCHING syndrome can present with RP, but they do not fit the abovementioned hierarchy and are thus categorized as miscellaneous.
Several first-in-human clinical trials are underway or in preparation for some of these syndromic forms of RP.
{"title":"Syndromic retinitis pigmentosa","authors":"Jessica S. Karuntu , Hind Almushattat , Xuan-Thanh-An Nguyen , Astrid S. Plomp , Ronald J.A. Wanders , Carel B. Hoyng , Mary J. van Schooneveld , Nicoline E. Schalij-Delfos , Marion M. Brands , Bart P. Leroy , Clara D.M. van Karnebeek , Arthur A. Bergen , Maria M. van Genderen , Camiel J.F. Boon","doi":"10.1016/j.preteyeres.2024.101324","DOIUrl":"10.1016/j.preteyeres.2024.101324","url":null,"abstract":"<div><div>Retinitis pigmentosa (RP) is a progressive inherited retinal dystrophy, characterized by the degeneration of photoreceptors, presenting as a rod-cone dystrophy. Approximately 20–30% of patients with RP also exhibit extra-ocular manifestations in the context of a syndrome. This manuscript discusses the broad spectrum of syndromes associated with RP, pathogenic mechanisms, clinical manifestations, differential diagnoses, clinical management approaches, and future perspectives. Given the diverse clinical and genetic landscape of syndromic RP, the diagnosis may be challenging. However, an accurate and timely diagnosis is essential for optimal clinical management, prognostication, and potential treatment. Broadly, the syndromes associated with RP can be categorized into ciliopathies, inherited metabolic disorders, mitochondrial disorders, and miscellaneous syndromes. Among the ciliopathies associated with RP, Usher syndrome and Bardet-Biedl syndrome are the most well-known. Less common ciliopathies include Cohen syndrome, Joubert syndrome, cranioectodermal dysplasia, asphyxiating thoracic dystrophy, Mainzer-Saldino syndrome, and RHYNS syndrome.</div><div>Several inherited metabolic disorders can present with RP, including Zellweger spectrum disorders, adult Refsum disease, α-methylacyl-CoA racemase deficiency, certain mucopolysaccharidoses, ataxia with vitamin E deficiency, abetalipoproteinemia, several neuronal ceroid lipofuscinoses, mevalonic aciduria, PKAN/HARP syndrome, PHARC syndrome, and methylmalonic acidaemia with homocystinuria type cobalamin (cbl) C disease.</div><div>Due to the mitochondria's essential role in supplying continuous energy to the retina, disruption of mitochondrial function can lead to RP, as seen in Kearns-Sayre syndrome, NARP syndrome, primary coenzyme Q10 deficiency, <em>SSBP1</em>-associated disease, and long chain 3-hydroxyacyl-CoA dehydrogenase deficiency. Lastly, Cockayne syndrome and PERCHING syndrome can present with RP, but they do not fit the abovementioned hierarchy and are thus categorized as miscellaneous.</div><div>Several first-in-human clinical trials are underway or in preparation for some of these syndromic forms of RP.</div></div>","PeriodicalId":21159,"journal":{"name":"Progress in Retinal and Eye Research","volume":"107 ","pages":"Article 101324"},"PeriodicalIF":18.6,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142903530","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 : 2025-07-01Epub Date: 2025-05-21DOI: 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 : 2025-07-01Epub Date: 2025-06-13DOI: 10.1016/j.preteyeres.2025.101378
Yali Jia , Tristan T. Hormel , Thomas S. Hwang , An-Lun Wu , Guangru B. Liang , Yukun Guo , Xiang Wei , Shuibin Ni , Yifan Jian , J. Peter Campbell , Steven T. Bailey , John C. Morrison , David Huang
Optical coherence tomography angiography (OCTA) is a volumetric, non-invasive, high-resolution vascular imaging modality capable of acquiring highly detailed visualizations of retinal microvasculature. It has become an important tool for diagnosis and prognosis in prevalent diseases and pathologies such as diabetic retinopathy, retinopathy of prematurity, and vein occlusions, as well as more rare conditions, including inherited retinal dystrophies. It is also useful for measuring treatment response and assessing which patients would benefit from treatment. Unlike dye-based angiography, OCTA eliminates risks such as anaphylaxis. It also often outperforms fundus photography in feature detection. However, conventional OCTA imaging has been limited by its small field of view, which restricts simultaneous visualization of the posterior pole and peripheral retina, causing single images to potentially miss widely spaced critical biomarkers and pathological features. Recent technological advances in widefield OCTA have addressed this limitation, extending the field of view to the mid-periphery and beyond. This breakthrough enhances the simultaneous detection of macular and peripheral retinal pathology and significantly broadens OCTA's diagnostic and research applications. This review explores the technical innovations enabling widefield OCTA and highlights its clinical utility across various conditions, emphasizing its growing importance as a powerful tool in ophthalmic practice and research.
{"title":"Widefield OCT angiography","authors":"Yali Jia , Tristan T. Hormel , Thomas S. Hwang , An-Lun Wu , Guangru B. Liang , Yukun Guo , Xiang Wei , Shuibin Ni , Yifan Jian , J. Peter Campbell , Steven T. Bailey , John C. Morrison , David Huang","doi":"10.1016/j.preteyeres.2025.101378","DOIUrl":"10.1016/j.preteyeres.2025.101378","url":null,"abstract":"<div><div>Optical coherence tomography angiography (OCTA) is a volumetric, non-invasive, high-resolution vascular imaging modality capable of acquiring highly detailed visualizations of retinal microvasculature. It has become an important tool for diagnosis and prognosis in prevalent diseases and pathologies such as diabetic retinopathy, retinopathy of prematurity, and vein occlusions, as well as more rare conditions, including inherited retinal dystrophies. It is also useful for measuring treatment response and assessing which patients would benefit from treatment. Unlike dye-based angiography, OCTA eliminates risks such as anaphylaxis. It also often outperforms fundus photography in feature detection. However, conventional OCTA imaging has been limited by its small field of view, which restricts simultaneous visualization of the posterior pole and peripheral retina, causing single images to potentially miss widely spaced critical biomarkers and pathological features. Recent technological advances in widefield OCTA have addressed this limitation, extending the field of view to the mid-periphery and beyond. This breakthrough enhances the simultaneous detection of macular and peripheral retinal pathology and significantly broadens OCTA's diagnostic and research applications. This review explores the technical innovations enabling widefield OCTA and highlights its clinical utility across various conditions, emphasizing its growing importance as a powerful tool in ophthalmic practice and research.</div></div>","PeriodicalId":21159,"journal":{"name":"Progress in Retinal and Eye Research","volume":"107 ","pages":"Article 101378"},"PeriodicalIF":18.6,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144289814","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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