Progress in Retinal and Eye Research最新文献

{"title":"Microglial regulation of the retinal vasculature in health and during the pathology associated with diabetes","authors":"Andrew I. Jobling ,&nbsp;Ursula Greferath ,&nbsp;Michael A. Dixon ,&nbsp;Pialuisa Quiriconi ,&nbsp;Belinda Eyar ,&nbsp;Anna K. van Koeverden ,&nbsp;Samuel A. Mills ,&nbsp;Kirstan A. Vessey ,&nbsp;Bang V. Bui ,&nbsp;Erica L. Fletcher","doi":"10.1016/j.preteyeres.2025.101349","DOIUrl":"10.1016/j.preteyeres.2025.101349","url":null,"abstract":"<div><div>The high metabolic demand of retinal neurons requires a precisely regulated vascular system that can deliver rapid changes in blood flow in response to neural need. In the retina, this is achieved via the action of a coordinated group of cells that form the neurovascular unit. While cells such as pericytes, Müller cells, and astrocytes have long been linked to neurovascular coupling, more recently the resident microglial population have also been implicated. In the healthy retina, microglia make extensive contact with blood vessels, as well as neuronal synapses, and are important in vascular patterning during development. Work in the brain and retina has recently indicated that microglia can directly regulate the local vasculature. In the retina, the fractalkine-Cx3cr1 signalling axis has been shown to induce local capillary constriction within the superficial vascular plexus via a mechanism involving components of the renin-angiotensin system. Furthermore, aberrant microglial induced vasoconstriction may be at the centre of early vascular reactivity changes observed in those with diabetes. This review summarizes the recent emerging evidence that microglia play multiple roles in retinal homeostasis especially in regulating the vasculature. We highlight what is known about the role of microglia under normal circumstances, and then build on this to discuss how microglia contribute to early vascular compromise during diabetes. Further understanding of the mechanisms of microglial-vascular regulation may allow alternate treatment strategies to be devised to reduce vascular pathology in diseases such as diabetic retinopathy.</div></div>","PeriodicalId":21159,"journal":{"name":"Progress in Retinal and Eye Research","volume":"106 ","pages":"Article 101349"},"PeriodicalIF":18.6,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143531012","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Spaceflight Associated Neuro-ocular Syndrome (SANS) and its countermeasures","authors":"Tuan Nguyen ,&nbsp;Joshua Ong ,&nbsp;Tyson Brunstetter ,&nbsp;C. Robert Gibson ,&nbsp;Brandon R. Macias ,&nbsp;Steven Laurie ,&nbsp;Thomas Mader ,&nbsp;Alan Hargens ,&nbsp;Jay C. Buckey ,&nbsp;Mimi Lan ,&nbsp;Peter Wostyn ,&nbsp;Cihan Kadipasaoglu ,&nbsp;Scott M. Smith ,&nbsp;Sara R. Zwart ,&nbsp;Benjamin J. Frankfort ,&nbsp;Sarah Aman ,&nbsp;Jessica M. Scott ,&nbsp;Ethan Waisberg ,&nbsp;Mouayad Masalkhi ,&nbsp;Andrew G. Lee","doi":"10.1016/j.preteyeres.2025.101340","DOIUrl":"10.1016/j.preteyeres.2025.101340","url":null,"abstract":"<div><div>Astronauts can develop a distinct collection of neuro-ophthalmic findings during long duration spaceflight, collectively known as Spaceflight Associated Neuro-ocular Syndrome (SANS). These clinical characteristics include optic disc edema, hyperopic refractive shifts, globe flattening, and chorioretinal folds, which may pose a health risk for future space exploration. Obtaining knowledge of SANS and countermeasures for its prevention is crucial for upcoming crewed space missions and warrants a multidisciplinary approach. This review examines the potential causes and countermeasures of SANS, including space anticipation glasses, lower body negative pressure, venoconstrictive thigh cuffs, impedance threshold devices, translaminar pressure gradient modulation, centrifugation, artificial gravity, pharmaceuticals, and precision nutritional supplementation. This paper highlights future research directions for understanding the genetic, anthropometric, behavioral, and environmental susceptibilities to SANS as well as how to use terrestrial analogs for testing future mitigation strategies.</div></div>","PeriodicalId":21159,"journal":{"name":"Progress in Retinal and Eye Research","volume":"106 ","pages":"Article 101340"},"PeriodicalIF":18.6,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143459333","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}

{"title":"The dark and bright sides of retinal G protein-coupled receptor (RGR) in vision and disease","authors":"Grace Ruddin ,&nbsp;Tess McCann ,&nbsp;John D. Fehilly ,&nbsp;Jodie Kearney ,&nbsp;Breandán N. Kennedy","doi":"10.1016/j.preteyeres.2025.101339","DOIUrl":"10.1016/j.preteyeres.2025.101339","url":null,"abstract":"<div><div>The visual chromophore 11-<em>cis</em>-retinal (11cRAL) is essential to vertebrate phototransduction and therefore, must be regenerated so vision can be sustained. 11cRAL regeneration mediated by the classical visual cycle is insufficient under photopic conditions. Expressed in the retinal pigment epithelium (RPE) and Müller glia, the retinal G protein-coupled receptor (RGR) can act as an alternative visual cycle photoisomerase, photogenerating 11cRAL in bright light conditions. While named a G protein-coupled receptor, RGR has no known coupled G protein. In the photoisomerase process, RGR bound all-<em>trans</em>-retinal (atRAL) is converted to 11cRAL. Here, we review how this core reaction integrates into RPE and Müller cell visual cycles. Significantly, mutations in human RGR are associated with inherited retinal degeneration and age-related macular degeneration, ocular diseases impairing vision. In this article, we comprehensively review 30 years of research into this membrane-bound protein, to comprehend RGR's <em>i)</em> biological role in vision, <em>ii)</em> association with ocular disease, <em>iii)</em> and surprising role in non-ocular function and disease. We discuss studies with opposing views on the proposed role of RGR as mediating a non-canonical visual cycle which photogenerates 11cRAL. We highlight knowledge gaps that current RGR research is addressing.</div></div>","PeriodicalId":21159,"journal":{"name":"Progress in Retinal and Eye Research","volume":"106 ","pages":"Article 101339"},"PeriodicalIF":18.6,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143441377","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A comprehensive scoping review of methodological approaches and clinical applications of tear fluid biomarkers","authors":"Marlies Gijs ,&nbsp;Nienke van de Sande ,&nbsp;Clémence Bonnet ,&nbsp;Jente Schmeetz ,&nbsp;Rosa Fernandes ,&nbsp;Sònia Travé-Huarte ,&nbsp;Marcela Huertas-Bello ,&nbsp;Jeremy Chung Bo Chiang ,&nbsp;Nikolay Boychev ,&nbsp;Shruti Sharma","doi":"10.1016/j.preteyeres.2025.101338","DOIUrl":"10.1016/j.preteyeres.2025.101338","url":null,"abstract":"<div><div>Tear fluid is an emerging source of disease biomarkers, drawing attention due to its quick, inexpensive, and non-invasive collection. The advancements in detection techniques enable the measurement of ultra-low biomarker levels from small sample volumes typical of tear fluid. The lack of standardized protocols for collection, processing, and analysis of tear fluid remains a significant challenge. To address this, we convened the Tear Research Network Review Taskforce in 2022 to review protocols from the past three decades, providing a comprehensive overview of the methodologies used in tear fluid biomarker research.</div><div>A total of 1484 articles published from January 1974 to May 2024 from two electronic databases, Embase and Ovid MEDLINE, were reviewed. An exponential increase in the number of articles on tear fluid biomarkers was observed from 2015 onwards. The two most commonly reported collection methods were; glass capillaries (45.2%), and Schirmer's strips (25%), with glass capillary tube collection remaining the most frequent method until 2019, when Schirmer's strips became the leading method. Most articles analyzed tear fluid proteins (65%) and focused on a single analyte (32.3%). In recent years, an increase was observed in the type and number of examined analytes.</div><div>The differences in the reported methodologies and protocols underscore the need for standardization and harmonization within the field of tear fluid biomarkers to minimize methodological differences and reduce variability in clinical outcomes. Consistent and detailed reporting is essential for improving the reproducibility and validity of tear fluid studies, in order to advance their potential clinical applications.</div></div>","PeriodicalId":21159,"journal":{"name":"Progress in Retinal and Eye Research","volume":"106 ","pages":"Article 101338"},"PeriodicalIF":18.6,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143426083","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prosthetic eye care – The current state of the art","authors":"Alexander C. Rokohl ,&nbsp;Keith R. Pine ,&nbsp;Nicola S. Pine ,&nbsp;Erik Gordon ,&nbsp;Janice Yeoman ,&nbsp;Jelmer S. Remmers ,&nbsp;Dyonne T. Hartong ,&nbsp;Ludwig M. Heindl","doi":"10.1016/j.preteyeres.2025.101337","DOIUrl":"10.1016/j.preteyeres.2025.101337","url":null,"abstract":"<div><div>After eye loss, a fast supply with a visually appealing prosthetic eye is not just a cosmetic solution, it is the key factor for a successful social, occupational, and psychological rehabilitation. For a long time, prosthetic eye care was based on acquired experiences, and there was a significant lack of systematic studies and peer-reviewed literature on this subject. However, in recent decades, research in the field of ocular prosthetics has been driven forward by ophthalmologists, ocularists, optometrists, ophthalmoplastic surgeons, and psychologists. Many essential findings have been made for improving the care of anophthalmic patients. In this extensive review, the current state of the art regarding prosthetic eye care based on the newest scientific findings is summarized. The broad focus includes important historical aspects in ocular prosthetics, in particular the historical development that led to ocularistic care with different prosthetic materials – cryolite glass and polymethyl methacrylate. Furthermore, epidemiology and etiology of eye loss, surgical techniques of eye removal as well as types and production of prosthetic eyes are set out. Important topics with new insights include psychological issues such as living with a prosthetic eye, treatment of children with anophthalmia and microphthalmia, as well as evidence-based prosthetic eye maintenance and handling. In addition, anophthalmic socket complications and associated treatment options with a focus on the common dry anophthalmic socket and post-enucleation socket syndromes were described in detail. Finally, we will speculate how the field of prosthetic eye care will develop in the future.</div></div>","PeriodicalId":21159,"journal":{"name":"Progress in Retinal and Eye Research","volume":"105 ","pages":"Article 101337"},"PeriodicalIF":18.6,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143410394","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative insights into the role of sex hormones in glaucoma among women and men","authors":"Sharon H. Zhao ,&nbsp;Christine K. Kim ,&nbsp;Tala Al-Khaled ,&nbsp;Margaret Ann Chervinko ,&nbsp;Anne Wishna ,&nbsp;Rukhsana G. Mirza ,&nbsp;Thasarat Sutabutr Vajaranant","doi":"10.1016/j.preteyeres.2025.101336","DOIUrl":"10.1016/j.preteyeres.2025.101336","url":null,"abstract":"<div><div>Baseline differences in sex hormone levels between males and females influence tissues including the brain and eye. To investigate the effects of estrogens and androgens on ocular physiology and glaucoma, we review the current literature on the influence of primary sex hormones on ocular function, glaucoma incidence and related parameters like intraocular pressure (IOP) at physiologic levels and related to hormone therapies in men and women. These articles reveal activity of estrogen, testosterone, and progesterone within ocular tissues including the retinal pigment epithelium and ciliary epithelium where they likely influence glaucoma pathophysiology through effects on ocular blood flow and aqueous outflow. A growing body of evidence demonstrates a protective role of estrogen in glaucoma. With fluctuations across a woman's lifetime through menstrual phases, pregnancy, and menopause, the general association seen is a lower risk of glaucoma and lower IOP with higher estrogen. Exogenous hormones in the form of oral contraceptive pills and hormone replacement therapy also appear to affect glaucoma risk, although published findings are inconsistent. Few studies have reported a positive association between IOP and serum testosterone, and men treated with androgen deprivation therapy have shown a reduced risk of glaucoma while masculinizing hormone therapies at supra-physiologic testosterone levels have significantly increased IOP. Sex hormone perturbations affect components of glaucoma pathogenesis including IOP and ocular blood flow and overlap with known risk factors like age and sex. Standardized studies are needed to further elucidate the roles of estrogen and testosterone in glaucoma risk and progression.</div></div>","PeriodicalId":21159,"journal":{"name":"Progress in Retinal and Eye Research","volume":"105 ","pages":"Article 101336"},"PeriodicalIF":18.6,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143081040","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RNA methylation homeostasis in ocular diseases: All eyes on Me","authors":"Jieling Tang ,&nbsp;Chuandi Zhou ,&nbsp;Fuxiang Ye ,&nbsp;Sipeng Zuo ,&nbsp;Min Zhou ,&nbsp;Linna Lu ,&nbsp;Peiwei Chai ,&nbsp;Xianqun Fan","doi":"10.1016/j.preteyeres.2025.101335","DOIUrl":"10.1016/j.preteyeres.2025.101335","url":null,"abstract":"<div><div>RNA methylation is a pivotal epigenetic modification that adjusts various aspects of RNA biology, including nuclear transport, stability, and the efficiency of translation for specific RNA candidates. The methylation of RNA involves the addition of methyl groups to specific bases and can occur at different sites, resulting in distinct forms, such as N6-methyladenosine (m⁶A), N1-methyladenosine (m¹A), 5-methylcytosine (m⁵C), and 7-methylguanosine (m⁷G). Maintaining an optimal equilibrium of RNA methylation is crucial for fundamental cellular activities such as cell survival, proliferation, and migration. The balance of RNA methylation is linked to various pathophysiological conditions, including senescence, cancer development, stress responses, and blood vessel formation, all of which are pivotal for comprehending a spectrum of eye diseases.</div><div>Recent findings have highlighted the significant role of diverse RNA methylation patterns in ophthalmological conditions such as age-related macular degeneration, diabetic retinopathy, cataracts, glaucoma, uveitis, retinoblastoma, uveal melanoma, thyroid eye disease, and myopia, which are critical for vision health. This thorough review endeavors to dissect the influence of RNA methylation on common and vision-impairing ocular disorders. It explores the nuanced roles that RNA methylation plays in key pathophysiological mechanisms, such as oxidative stress and angiogenesis, which are integral to the onset and progression of these diseases. By synthesizing the latest research, this review offers valuable insights into how RNA methylation could be harnessed for therapeutic interventions in the field of ophthalmology.</div></div>","PeriodicalId":21159,"journal":{"name":"Progress in Retinal and Eye Research","volume":"105 ","pages":"Article 101335"},"PeriodicalIF":18.6,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143067624","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}

{"title":"Exploring retinal conditions through blue light reflectance imaging","authors":"Ricardo Luz Leitão Guerra ,&nbsp;Cezar Luz Leitão Guerra ,&nbsp;Mariana Gouveia Bastos Meirelles ,&nbsp;Gabriel Castilho Sandoval Barbosa ,&nbsp;Eduardo Amorim Novais ,&nbsp;Emmerson Badaró ,&nbsp;Luiz Filipe Adami Lucatto ,&nbsp;Luiz Roisman","doi":"10.1016/j.preteyeres.2024.101326","DOIUrl":"10.1016/j.preteyeres.2024.101326","url":null,"abstract":"<div><div>Blue light reflectance (BLR) imaging offers a non-invasive, cost-effective method for evaluating retinal structures by analyzing the reflectance and absorption characteristics of the inner retinal layers. By leveraging blue light's interaction with retinal tissues, BLR enhances visualization beyond the retinal nerve fiber layer, improving detection of structures such as the outer plexiform layer and macular pigment. Its diagnostic utility has been demonstrated in distinct retinal conditions, including hyperreflectance in early macular telangiectasia, hyporeflectance in non-perfused areas indicative of ischemia, identification of pseudodrusen patterns (notably the ribbon type), and detection of peripheral retinal tears and degenerative retinoschisis in eyes with reduced retinal pigment epithelial pigmentation. Best practices for image acquisition and interpretation are discussed, emphasizing standardization to minimize variability. Common artifacts and mitigation strategies are also addressed, ensuring image reliability. BLR's clinical utility, limitations, and future research directions are highlighted, particularly its potential in automated image analysis and quantitative assessment. Different BLR acquisition methods, such as fundus photography, confocal scanning laser ophthalmoscopy, and broad line fundus imaging, are evaluated for their respective advantages and limitations. As research advances, BLR's integration into multimodal workflows is expected to improve early detection and precise monitoring of retinal diseases.</div></div>","PeriodicalId":21159,"journal":{"name":"Progress in Retinal and Eye Research","volume":"105 ","pages":"Article 101326"},"PeriodicalIF":18.6,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142932486","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}

{"title":"Extensive macular atrophy with pseudodrusen-like appearance (EMAP) clinical characteristics, diagnostic criteria, and insights from allied inherited retinal diseases and age-related macular degeneration","authors":"Alessio Antropoli ,&nbsp;Lorenzo Bianco ,&nbsp;Francesco Romano ,&nbsp;Andrea Trinco ,&nbsp;Alessandro Arrigo ,&nbsp;Amine Benadji ,&nbsp;Raphaël Atia ,&nbsp;Oana Palacci ,&nbsp;Dorothée Dagostinoz ,&nbsp;Céline Devisme ,&nbsp;Christel Condroyer ,&nbsp;Aline Antonio ,&nbsp;Francesca Bosello ,&nbsp;Stefano Casati ,&nbsp;Anna Paola Salvetti ,&nbsp;Chiara Zaffalon ,&nbsp;Alain Gaudric ,&nbsp;José-Alain Sahel ,&nbsp;Giovanni Staurenghi ,&nbsp;Francesco Bandello ,&nbsp;Isabelle Audo","doi":"10.1016/j.preteyeres.2024.101320","DOIUrl":"10.1016/j.preteyeres.2024.101320","url":null,"abstract":"<div><div>Extensive macular atrophy with pseudodrusen-like appearance (EMAP) was first described in France in 2009 as a symmetric and rapidly progressive form of macular atrophy primarily affecting middle-aged individuals. Despite the recent identification of a significant number of cases in Italy and worldwide, EMAP remains an underrecognized condition. The clinical triad typical of EMAP consists of vertically oriented macular atrophy with multilobular borders, pseudodrusen-like deposits across the posterior pole and mid-periphery, and peripheral pavingstone degeneration. Nonetheless, recent research has portrayed EMAP as a highly stage-dependent condition, allowing the identification of novel disease hallmarks, including a diffuse separation between the Bruch’s membrane and the retinal pigment epithelium, along with consistent sparing of a region temporal to the macula. Additionally, retinal electrophysiology is particularly useful in distinguishing EMAP from age-related macular degeneration (AMD).</div><div>Supported by unpublished data from the largest EMAP cohorts worldwide, this review aims to provide a comprehensive and updated description of EMAP, now recognized as a severely blinding disease characterized by diffuse chorioretinal atrophy and photoreceptor dysfunction. Furthermore, we propose a set of diagnostic criteria that incorporate clinical, imaging, and functional tests, to facilitate the recognition of this clinical entity. Lastly, we aim to shed light on its pathogenesis by comparing it with AMD and monogenic retinal disorders exhibiting similar phenotypes.</div></div>","PeriodicalId":21159,"journal":{"name":"Progress in Retinal and Eye Research","volume":"104 ","pages":"Article 101320"},"PeriodicalIF":18.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142740381","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corneal cross-linking","authors":"Farhad Hafezi ,&nbsp;Sabine Kling ,&nbsp;Nikki L. Hafezi ,&nbsp;M. Enes Aydemir ,&nbsp;Nan-Ji Lu ,&nbsp;Mark Hillen ,&nbsp;Boris Knyazer ,&nbsp;Shady Awwad ,&nbsp;Cosimo Mazzotta ,&nbsp;Léonard Kollros ,&nbsp;Emilio A. Torres-Netto","doi":"10.1016/j.preteyeres.2024.101322","DOIUrl":"10.1016/j.preteyeres.2024.101322","url":null,"abstract":"<div><div>First introduced over 20 years ago as a treatment for progressive keratoconus, the original “Dresden” corneal cross-linking (CXL) protocol involved riboflavin saturation of the stroma, followed by 30 min of 3 mW/cm²-intensity ultraviolet-A (UV-A) irradiation. This procedure generates reactive oxygen species (ROS) that cross-link stromal molecules, thereby stiffening the cornea and counteracting the ectasia-induced weakening. Due to their large size, riboflavin molecules cannot readily pass through the corneal epithelial cell tight junctions; thus, epithelial debridement was performed. Moreover, the Dresden protocol necessitates a minimal corneal thickness of 400 μm to protect the endothelium from UV-induced damage. While the Dresden protocol is highly effective at enhancing corneal biomechanical strength, there was a strong desire for CXL procedures that would deliver Dresden-like strengthening in a shorter time, in corneas thinner than 400 μm, and without requiring epithelial debridement.</div><div>This review explores the advancements and scientific discoveries that have enabled such improvements. Accelerated CXL protocols, utilizing our increased knowledge about the role of oxygen and photochemical reactions in the cornea have shortened and simplified the procedure duration while maintaining efficacy and safety, improving clinical workflow and patient compliance.</div><div>CXL is not confined to improving biomechanics in corneal ectasia, but rather represents a technique that modulates corneal physiology and biochemistry on multiple levels. Accordingly, CXL indications have expanded to include treating other corneal ectasias, corneal neovascularization, corneal sterile melting, inflammatory dry eye and importantly, infectious keratitis in a procedure termed photoactivated chromophore for keratitis-CXL (PACK-CXL). In PACK-CXL, ROS have a direct pathogen-killing effect, and cross-linking enhances the cornea's resistance to pathogen-produced protease digestion through steric hindrance.</div><div>The distinct requirements of PACK-CXL compared to ectasia treatment have led to the development of different CXL protocols, including higher UV fluences and other chromophore/light combinations, specifically rose bengal and green light. Additionally, combining CXL with vision-enhancing procedures like individualized wavefront- or topographically-guided excimer ablation can regularize a biomechanically stable cornea, improve visual acuity, and potentially eliminate the need for corneal transplantation, leading to long-term improvements in quality of life.</div></div>","PeriodicalId":21159,"journal":{"name":"Progress in Retinal and Eye Research","volume":"104 ","pages":"Article 101322"},"PeriodicalIF":18.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142838404","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}