Chieh-Lin Stanley Wu, Adrian V Cioanca, Maria C Gelmi, Li Wen, Nick Di Girolamo, Ling Zhu, Riccardo Natoli, R Max Conway, Constantinos Petsoglou, Martine J Jager, Peter J McCluskey, Michele C Madigan
{"title":"Corrigendum to \"The multifunctional human ocular melanocortin system\" [Prog. Retin. Eye Res. 95 (2023) 1-23 101187].","authors":"Chieh-Lin Stanley Wu, Adrian V Cioanca, Maria C Gelmi, Li Wen, Nick Di Girolamo, Ling Zhu, Riccardo Natoli, R Max Conway, Constantinos Petsoglou, Martine J Jager, Peter J McCluskey, Michele C Madigan","doi":"10.1016/j.preteyeres.2025.101355","DOIUrl":"https://doi.org/10.1016/j.preteyeres.2025.101355","url":null,"abstract":"","PeriodicalId":21159,"journal":{"name":"Progress in Retinal and Eye Research","volume":" ","pages":"101355"},"PeriodicalIF":18.6,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143780960","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}
Benjamin Phipps , Xavier Hadoux , Bin Sheng , J. Peter Campbell , T.Y. Alvin Liu , Pearse A. Keane , Carol Y. Cheung , Tham Yih Chung , Tien Y. Wong , Peter van Wijngaarden
{"title":"AI image generation technology in ophthalmology: Use, misuse and future applications","authors":"Benjamin Phipps , Xavier Hadoux , Bin Sheng , J. Peter Campbell , T.Y. Alvin Liu , Pearse A. Keane , Carol Y. Cheung , Tham Yih Chung , Tien Y. Wong , Peter van Wijngaarden","doi":"10.1016/j.preteyeres.2025.101353","DOIUrl":"10.1016/j.preteyeres.2025.101353","url":null,"abstract":"<div><h3>Background</h3><div>AI-powered image generation technology holds the potential to reshape medical practice, yet it remains an unfamiliar technology for both medical researchers and clinicians alike. Given the adoption of this technology relies on clinician understanding and acceptance, we sought to demystify its use in ophthalmology. To this end, we present a literature review on image generation technology in ophthalmology, examining both its theoretical applications and future role in clinical practice.</div></div><div><h3>Methods</h3><div>First, we consider the key model designs used for image synthesis, including generative adversarial networks, autoencoders, and diffusion models. We then perform a survey of the literature for image generation technology in ophthalmology prior to September 2024, presenting both the type of model used and its clinical application. Finally, we discuss the limitations of this technology, the risks of its misuse and the future directions of research in this field.</div></div><div><h3>Results</h3><div>Applications of this technology include improving AI diagnostic models, inter-modality image transformation, more accurate treatment and disease prognostication, image denoising, and individualised education. Key barriers to its adoption include bias in generative models, risks to patient data security, computational and logistical barriers to development, challenges with model explainability, inconsistent use of validation metrics between studies and misuse of synthetic images. Looking forward, researchers are placing a further emphasis on clinically grounded metrics, the development of image generation foundation models and the implementation of methods to ensure data provenance.</div></div><div><h3>Conclusion</h3><div>Compared to other medical applications of AI, image generation is still in its infancy. Yet, it holds the potential to revolutionise ophthalmology across research, education and clinical practice. This review aims to guide ophthalmic researchers wanting to leverage this technology, while also providing an insight for clinicians on how it may change ophthalmic practice in the future.</div></div>","PeriodicalId":21159,"journal":{"name":"Progress in Retinal and Eye Research","volume":"106 ","pages":"Article 101353"},"PeriodicalIF":18.6,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143664402","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}
Ryan Purdy , Molly John , Alissa Bray , Alison J. Clare , David A. Copland , Ying Kai Chan , Robert H. Henderson , Fanny Nerinckx , Bart P. Leroy , Paul Yang , Mark E. Pennesi , Robert E. MacLaren , M Dominik Fischer , Andrew D. Dick , Kanmin Xue
{"title":"Gene Therapy-Associated Uveitis (GTAU): Understanding and mitigating the adverse immune response in retinal gene therapy","authors":"Ryan Purdy , Molly John , Alissa Bray , Alison J. Clare , David A. Copland , Ying Kai Chan , Robert H. Henderson , Fanny Nerinckx , Bart P. Leroy , Paul Yang , Mark E. Pennesi , Robert E. MacLaren , M Dominik Fischer , Andrew D. Dick , Kanmin Xue","doi":"10.1016/j.preteyeres.2025.101354","DOIUrl":"10.1016/j.preteyeres.2025.101354","url":null,"abstract":"<div><div>Retinal gene therapy using adeno-associated viral (AAV) vectors has been a groundbreaking step-change in the treatment of inherited retinal diseases (IRDs) and could also be used to treat more common retinal diseases such as age-related macular degeneration and diabetic retinopathy. The delivery and expression of therapeutic transgenes in the eye is limited by innate and adaptive immune responses against components of the vector product, which has been termed gene therapy-associated uveitis (GTAU). This is clinically important as intraocular inflammation could lead to irreversible loss of retinal cells, deterioration of visual function and reduced durability of treatment effect associated with a costly one-off treatment. For retinal gene therapy to achieve an improved efficacy and safety profile for treating additional IRDs and more common diseases, the risk of GTAU must be minimised. We have collated insights from pre-clinical research, clinical trials, and the real-world implementation of AAV-mediated retinal gene therapy to help understand the risk factors for GTAU. We draw attention to an emerging framework, which includes patient demographics, vector construct, vector dose, route of administration, and choice of immunosuppression regime. Importantly, we consider efforts to date and potential future strategies to mitigate the adverse immune response across each of these domains. We advocate for more targeted immunomodulatory approaches to the prevention and treatment of GTAU based on better understanding of the underlying immune response.</div></div>","PeriodicalId":21159,"journal":{"name":"Progress in Retinal and Eye Research","volume":"106 ","pages":"Article 101354"},"PeriodicalIF":18.6,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143639657","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}
Songyang An , Kelvin Teo , Michael V. McConnell , John Marshall , Christopher Galloway , David Squirrell
{"title":"AI explainability in oculomics: How it works, its role in establishing trust, and what still needs to be addressed","authors":"Songyang An , Kelvin Teo , Michael V. McConnell , John Marshall , Christopher Galloway , David Squirrell","doi":"10.1016/j.preteyeres.2025.101352","DOIUrl":"10.1016/j.preteyeres.2025.101352","url":null,"abstract":"<div><div>Recent developments in artificial intelligence (AI) have seen a proliferation of algorithms that are now capable of predicting a range of systemic diseases from retinal images. Unlike traditional retinal disease detection AI models which are trained on well-recognised retinal biomarkers, systemic disease detection or “oculomics” models use a range of often poorly characterised retinal biomarkers to arrive at their predictions. As the retinal phenotype that oculomics models use may not be intuitive, clinicians have to rely on the developers’ explanations of how these algorithms work in order to understand them. The discipline of understanding how AI algorithms work employs two similar but distinct terms: Explainable AI and Interpretable AI (iAI). Explainable AI describes the holistic functioning of an AI system, including its impact and potential biases. Interpretable AI concentrates solely on examining and understanding the workings of the AI algorithm itself. iAI tools are therefore what the clinician must rely on if they are to understand how the algorithm works and whether its predictions are reliable. The iAI tools that developers use can be delineated into two broad categories: Intrinsic methods that improve transparency through architectural changes and post-hoc methods that explain trained models via external algorithms. Currently post-hoc methods, class activation maps in particular, are far more widely used than other techniques but they have their limitations especially when applied to oculomics AI models. Aimed at clinicians, we examine how the key iAI methods work, what they are designed to do and what their limitations are when applied to oculomics AI. We conclude by discussing how combining existing iAI techniques with novel approaches could allow AI developers to better explain how their oculomics models work and reassure clinicians that the results issued are reliable.</div></div>","PeriodicalId":21159,"journal":{"name":"Progress in Retinal and Eye Research","volume":"106 ","pages":"Article 101352"},"PeriodicalIF":18.6,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143630829","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}
Alessandro Feo , Prithvi Ramtohul , Andrea Govetto , Enrico Borrelli , Riccardo Sacconi , Giulia Corradetti , Giuseppe Querques , Mario R. Romano , Philip J. Rosenfeld , Richard F. Spaide , K Bailey Freund , SriniVas Sadda , David Sarraf
{"title":"En face OCT: Breakthroughs in understanding the pathoanatomy of retinal disease and clinical applications","authors":"Alessandro Feo , Prithvi Ramtohul , Andrea Govetto , Enrico Borrelli , Riccardo Sacconi , Giulia Corradetti , Giuseppe Querques , Mario R. Romano , Philip J. Rosenfeld , Richard F. Spaide , K Bailey Freund , SriniVas Sadda , David Sarraf","doi":"10.1016/j.preteyeres.2025.101351","DOIUrl":"10.1016/j.preteyeres.2025.101351","url":null,"abstract":"<div><div>En face optical coherence tomography (OCT) is a practical and informative imaging modality to noninvasively visualize distinct retinal and choroidal layers by providing coronal images using boundary-specific segmentation. Ongoing research with this method is generating breakthroughs in the illustration of new perspectives of retinal disease. The clinical value of en face OCT as an advanced retinal imaging tool is growing steadily and it has unveiled many new insights into the pathoanatomy of retinal disorders. Moreover, this modality can capture various en face OCT biomarkers that correspond to different cell or tissue subtypes, which were previously only identified through histological or electron microscopy methods, underscoring the significance of this technique in providing valuable pathoanatomical information.</div><div>In this comprehensive review, we will systematically summarize the en face OCT findings across a broad spectrum of retinal diseases, including disorders of the vitreoretinal interface and retinal vascular system (e.g. paracentral acute middle maculopathy or PAMM and diabetic retinopathy), in addition to the en face OCT features of other conditions such as age-related macular degeneration, pachychoroid disease spectrum, myopic degeneration, uveitis and inflammatory disorders, inherited retinal dystrophies, and drug toxicity. We will discuss and highlight the unique clinical and pathoanatomical findings uncovered with en face OCT of each these diseases mentioned above.</div></div>","PeriodicalId":21159,"journal":{"name":"Progress in Retinal and Eye Research","volume":"106 ","pages":"Article 101351"},"PeriodicalIF":18.6,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143586585","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}
Zhuoting Zhu , Yueye Wang , Ziyi Qi , Wenyi Hu , Xiayin Zhang , Siegfried K. Wagner , Yujie Wang , An Ran Ran , Joshua Ong , Ethan Waisberg , Mouayad Masalkhi , Alex Suh , Yih Chung Tham , Carol Y. Cheung , Xiaohong Yang , Honghua Yu , Zongyuan Ge , Wei Wang , Bin Sheng , Yun Liu , Tien Yin Wong
{"title":"Oculomics: Current concepts and evidence","authors":"Zhuoting Zhu , Yueye Wang , Ziyi Qi , Wenyi Hu , Xiayin Zhang , Siegfried K. Wagner , Yujie Wang , An Ran Ran , Joshua Ong , Ethan Waisberg , Mouayad Masalkhi , Alex Suh , Yih Chung Tham , Carol Y. Cheung , Xiaohong Yang , Honghua Yu , Zongyuan Ge , Wei Wang , Bin Sheng , Yun Liu , Tien Yin Wong","doi":"10.1016/j.preteyeres.2025.101350","DOIUrl":"10.1016/j.preteyeres.2025.101350","url":null,"abstract":"<div><div>The eye provides novel insights into general health, as well as pathogenesis and development of systemic diseases. In the past decade, growing evidence has demonstrated that the eye's structure and function mirror multiple systemic health conditions, especially in cardiovascular diseases, neurodegenerative disorders, and kidney impairments. This has given rise to the field of oculomics-the application of ophthalmic biomarkers to understand mechanisms, detect and predict disease. The development of this field has been accelerated by three major advances: 1) the availability and widespread clinical adoption of high-resolution and non-invasive ophthalmic imaging (“hardware”); 2) the availability of large studies to interrogate associations (“big data”); 3) the development of novel analytical methods, including artificial intelligence (AI) (“software”). Oculomics offers an opportunity to enhance our understanding of the interplay between the eye and the body, while supporting development of innovative diagnostic, prognostic, and therapeutic tools. These advances have been further accelerated by developments in AI, coupled with large-scale linkage datasets linking ocular imaging data with systemic health data. Oculomics also enables the detection, screening, diagnosis, and monitoring of many systemic health conditions. Furthermore, oculomics with AI allows prediction of the risk of systemic diseases, enabling risk stratification, opening up new avenues for prevention or individualized risk prediction and prevention, facilitating personalized medicine. In this review, we summarise current concepts and evidence in the field of oculomics, highlighting the progress that has been made, remaining challenges, and the opportunities for future research.</div></div>","PeriodicalId":21159,"journal":{"name":"Progress in Retinal and Eye Research","volume":"106 ","pages":"Article 101350"},"PeriodicalIF":18.6,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143573856","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}
Andrew I. Jobling , Ursula Greferath , Michael A. Dixon , Pialuisa Quiriconi , Belinda Eyar , Anna K. van Koeverden , Samuel A. Mills , Kirstan A. Vessey , Bang V. Bui , Erica L. Fletcher
{"title":"Microglial regulation of the retinal vasculature in health and during the pathology associated with diabetes","authors":"Andrew I. Jobling , Ursula Greferath , Michael A. Dixon , Pialuisa Quiriconi , Belinda Eyar , Anna K. van Koeverden , Samuel A. Mills , Kirstan A. Vessey , Bang V. Bui , 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}
Tuan Nguyen , Joshua Ong , Tyson Brunstetter , C. Robert Gibson , Brandon R. Macias , Steven Laurie , Thomas Mader , Alan Hargens , Jay C. Buckey , Mimi Lan , Peter Wostyn , Cihan Kadipasaoglu , Scott M. Smith , Sara R. Zwart , Benjamin J. Frankfort , Sarah Aman , Jessica M. Scott , Ethan Waisberg , Mouayad Masalkhi , Andrew G. Lee
{"title":"Spaceflight Associated Neuro-ocular Syndrome (SANS) and its countermeasures","authors":"Tuan Nguyen , Joshua Ong , Tyson Brunstetter , C. Robert Gibson , Brandon R. Macias , Steven Laurie , Thomas Mader , Alan Hargens , Jay C. Buckey , Mimi Lan , Peter Wostyn , Cihan Kadipasaoglu , Scott M. Smith , Sara R. Zwart , Benjamin J. Frankfort , Sarah Aman , Jessica M. Scott , Ethan Waisberg , Mouayad Masalkhi , 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}
Grace Ruddin , Tess McCann , John D. Fehilly , Jodie Kearney , Breandán N. Kennedy
{"title":"The dark and bright sides of retinal G protein-coupled receptor (RGR) in vision and disease","authors":"Grace Ruddin , Tess McCann , John D. Fehilly , Jodie Kearney , 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}
Marlies Gijs , Nienke van de Sande , Clémence Bonnet , Jente Schmeetz , Rosa Fernandes , Sònia Travé-Huarte , Marcela Huertas-Bello , Jeremy Chung Bo Chiang , Nikolay Boychev , Shruti Sharma
{"title":"A comprehensive scoping review of methodological approaches and clinical applications of tear fluid biomarkers","authors":"Marlies Gijs , Nienke van de Sande , Clémence Bonnet , Jente Schmeetz , Rosa Fernandes , Sònia Travé-Huarte , Marcela Huertas-Bello , Jeremy Chung Bo Chiang , Nikolay Boychev , 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}