Ocular blood flow imaging techniques have become indispensable in current clinical practice because retinal vascular disturbances have been implicated in the pathophysiology of numerous ocular diseases. In this review, we explore the applications of laser Doppler flowmetry, laser speckle flowgraphy (LSFG), and optical coherence tomography angiography (OCTA), focusing on LSFG and OCTA. Each modality is discussed in detail, including its principles, key parameters, advantages, limitations, and common artifacts. We further evaluated their roles in several ocular diseases, including age-related macular degeneration, polypoidal choroidal vasculopathy, diabetic retinopathy, retinal vein occlusion, retinal artery occlusion, pathologic myopia, glaucoma, non-arteritic anterior ischemic optic neuropathy, and retinopathy of prematurity. Finally, we discuss emerging advancements such as neonatal imaging devices, ultrawide-field OCTA, and artificial intelligence integration in vascular analysis.
{"title":"Advancements in ocular blood flow imaging: Clinical applications of laser speckle flowgraphy and optical coherence tomography angiography in retinal and choroidal vascular diseases","authors":"Yi-Hsuan Tseng , Pei-Liang Wu , Eugene Yu-Chuan Kang MD , Kuan-Jen Chen MD , Po-Han Yeh MD , Ling Yeung MD , Ming-hui Sun MD, PhD , Nan-Kai Wang MD, PhD , Yih-Shiou Hwang MD, PhD , Chi-Chun Lai MD , Wei-Chi Wu MD, PhD","doi":"10.1016/j.survophthal.2025.09.016","DOIUrl":"10.1016/j.survophthal.2025.09.016","url":null,"abstract":"<div><div>Ocular blood flow imaging techniques have become indispensable in current clinical practice because retinal vascular disturbances have been implicated in the pathophysiology of numerous ocular diseases. In this review, we explore the applications of laser Doppler flowmetry, laser speckle flowgraphy (LSFG), and optical coherence tomography angiography (OCTA), focusing on LSFG and OCTA. Each modality is discussed in detail, including its principles, key parameters, advantages, limitations, and common artifacts. We further evaluated their roles in several ocular diseases, including age-related macular degeneration, polypoidal choroidal vasculopathy, diabetic retinopathy, retinal vein occlusion, retinal artery occlusion, pathologic myopia, glaucoma, non-arteritic anterior ischemic optic neuropathy, and retinopathy of prematurity. Finally, we discuss emerging advancements such as neonatal imaging devices, ultrawide-field OCTA, and artificial intelligence integration in vascular analysis.</div></div>","PeriodicalId":22102,"journal":{"name":"Survey of ophthalmology","volume":"71 2","pages":"Pages 627-646"},"PeriodicalIF":5.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145131822","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Fluorescein angiography (FA) has long been a cornerstone for evaluating retinal vascular leakage in diseases like uveitis, diabetic retinopathy, and macular degeneration, but its interpretation relies on subjective grading that can vary between clinicians. With the emergence of artificial intelligence (AI), there is a push to transform this qualitative assessment into objective, quantifiable metrics. We conducted a comprehensive literature search using PubMed, Embase, and Scopus, combining keywords and MeSH terms related to fluorescein angiography leakage, artificial intelligence, and retinal vascular diseases. Studies were included if they assessed FA leakage using manual, semi-automated, or AI-based methods and were peer-reviewed, published in English, and focused on human subjects. Our review charts the evolution from manual grading to modern machine learning techniques that segment and measure leakage using various angiograms. These AI-based approaches enable standardized, reproducible leakage indices that correlate with disease severity, inform treatment decisions, stratify high-risk patients, and facilitate sensitive monitoring of therapeutic response. We also introduce the concept of “minimal residual disease” in this context. By moving from coarse, subjective estimations to precise digital biomarkers, AI-driven FA leakage quantification promises to improve clinical care and research endpoints in retinal disease.
{"title":"Detection and quantification of fluorescein angiography leakage: From manual grading to advances in machine learning","authors":"Uday Pratap Singh Parmar M.B.B.S , Atul Arora M.S , Aniruddha Agarwal M.S , Sapna Gangaputra M.D , Rupesh Agrawal F.R.C.S , Vishali Gupta M.S.","doi":"10.1016/j.survophthal.2025.08.015","DOIUrl":"10.1016/j.survophthal.2025.08.015","url":null,"abstract":"<div><div>Fluorescein angiography (FA) has long been a cornerstone for evaluating retinal vascular leakage in diseases like uveitis, diabetic retinopathy, and macular degeneration, but its interpretation relies on subjective grading that can vary between clinicians. With the emergence of artificial intelligence (AI), there is a push to transform this qualitative assessment into objective, quantifiable metrics. We conducted a comprehensive literature search using PubMed, Embase, and Scopus, combining keywords and MeSH terms related to fluorescein angiography leakage, artificial intelligence, and retinal vascular diseases. Studies were included if they assessed FA leakage using manual, semi-automated, or AI-based methods and were peer-reviewed, published in English, and focused on human subjects. Our review charts the evolution from manual grading to modern machine learning techniques that segment and measure leakage using various angiograms. These AI-based approaches enable standardized, reproducible leakage indices that correlate with disease severity, inform treatment decisions, stratify high-risk patients, and facilitate sensitive monitoring of therapeutic response. We also introduce the concept of “minimal residual disease” in this context. By moving from coarse, subjective estimations to precise digital biomarkers, AI-driven FA leakage quantification promises to improve clinical care and research endpoints in retinal disease.</div></div>","PeriodicalId":22102,"journal":{"name":"Survey of ophthalmology","volume":"71 2","pages":"Pages 613-626"},"PeriodicalIF":5.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144993309","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-03-01Epub Date: 2025-09-04DOI: 10.1016/j.survophthal.2025.09.001
Ramesh Venkatesh Dr. , Pratibha Hande Dr. , Vishma Prabhu Dr. , Shruthi Vidyasagar Dr. , Karishma Tendulkar Dr. , Rupak Roy Dr. , Kanika Godani Dr. , Alisha Sirsikar Dr. , Preksha Biradar Dr. , Priyanka Gandhi Dr. , Naresh Kumar Yadav Dr. , Jay Chhablani Dr.
Fundus tessellation (FT)—also referred to as tigroid or mosaic fundus—is characterized by increased visibility of underlying choroidal vessels. While often a physiological finding, FT may also signal early pathology in conditions such as high myopia, choroidal atrophy, or pigmentary disorders. We synthesize current understanding of the anatomical, optical, and imaging factors influencing FT appearance, including the roles of axial elongation, melanin distribution, and media clarity. Advances in multimodal imaging—such as color fundus photography, optical coherence tomography, and fundus autofluorescence—have improved the ability to differentiate physiological FT from disease-associated changes. Furthermore, artificial intelligence–driven tools like the Fundus Tessellation Density Index (FTDI) provide quantitative support for clinical decision-making. We propose a structured framework combining clinical parameters, imaging features, and FTDI to guide diagnosis and risk assessment. We underscore the clinical relevance of accurately distinguishing physiological from pathological FT and highlights directions for future research, including the potential of FTDI as a prognostic biomarker.
{"title":"Dissecting the clinical and pathophysiological complexity of fundus tessellation","authors":"Ramesh Venkatesh Dr. , Pratibha Hande Dr. , Vishma Prabhu Dr. , Shruthi Vidyasagar Dr. , Karishma Tendulkar Dr. , Rupak Roy Dr. , Kanika Godani Dr. , Alisha Sirsikar Dr. , Preksha Biradar Dr. , Priyanka Gandhi Dr. , Naresh Kumar Yadav Dr. , Jay Chhablani Dr.","doi":"10.1016/j.survophthal.2025.09.001","DOIUrl":"10.1016/j.survophthal.2025.09.001","url":null,"abstract":"<div><div>Fundus tessellation (FT)—also referred to as tigroid or mosaic fundus—is characterized by increased visibility of underlying choroidal vessels. While often a physiological finding, FT may also signal early pathology in conditions such as high myopia, choroidal atrophy, or pigmentary disorders. We synthesize current understanding of the anatomical, optical, and imaging factors influencing FT appearance, including the roles of axial elongation, melanin distribution, and media clarity. Advances in multimodal imaging—such as color fundus photography, optical coherence tomography, and fundus autofluorescence—have improved the ability to differentiate physiological FT from disease-associated changes. Furthermore, artificial intelligence–driven tools like the Fundus Tessellation Density Index (FTDI) provide quantitative support for clinical decision-making. We propose a structured framework combining clinical parameters, imaging features, and FTDI to guide diagnosis and risk assessment. We underscore the clinical relevance of accurately distinguishing physiological from pathological FT and highlights directions for future research, including the potential of FTDI as a prognostic biomarker.</div></div>","PeriodicalId":22102,"journal":{"name":"Survey of ophthalmology","volume":"71 2","pages":"Pages 382-392"},"PeriodicalIF":5.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145008437","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-03-01Epub Date: 2025-06-18DOI: 10.1016/j.survophthal.2025.06.009
Leon von der Emde , Simon M. Petzinna , Martina C. Herwig-Carl , Maike S. Adamson , Claus-Juergen Bauer , Julia Esser , Alexander Isaak , Katharina Wall , Jan H. Terheyden , Frank G. Holz , Valentin S. Schäfer , Thomas Ach
Giant cell arteritis (GCA) is an autoimmune disease of medium and large sized vessels. It is the most prevalent form of primary vasculitis in the western world. Vascular inflammation in GCA can lead to vascular occlusion. Severe neuro-ophthalmological complications, such as arteritic anterior ischemic optic neuropathy (AAION), may present with sudden partial or complete vision loss or diplopia. Visual impairment is often refractory to corticosteroid therapy, underscoring the critical importance of early diagnosis. Delayed diagnosis and initiation of high-dose corticosteroids can lead to contralateral eye involvement and bilateral irreversible vision loss. Recent advances in expedited diagnostics have significantly improved outcomes in GCA patients, particularly by reducing ischemic neuro-ophthalmological events. Thus, a key factor has been the introduction of Fast-Track Clinics that have successfully decreased the incidence of permanent blindness in GCA patients. In these clinics, imaging modalities such as vascular ultrasound, magnetic resonance imaging, and positron emission tomography-computed tomography play a critical role in both diagnosis and disease monitoring, enabling timely and accurate intervention. On the therapeutic front, cytokine-specific inhibitors have improved GCA management, enhancing remission rates and reducing glucocorticoid use. Tocilizumab, an IL-6 receptor (IL-6R) inhibitor, has become a cornerstone of GCA treatment; however, since some patients do not respond to IL-6R inhibition, ongoing research is exploring alternative disease-modifying therapies. These new approaches aim to reduce glucocorticoid dependency, mitigate side effects, enhance visual outcomes, and improve patient outcomes, highlighting a shift towards more individualized treatment approaches.
{"title":"Advances in diagnosing and treating giant cell arteritis: New hope for arteritic anterior ischemic optic neuropathy","authors":"Leon von der Emde , Simon M. Petzinna , Martina C. Herwig-Carl , Maike S. Adamson , Claus-Juergen Bauer , Julia Esser , Alexander Isaak , Katharina Wall , Jan H. Terheyden , Frank G. Holz , Valentin S. Schäfer , Thomas Ach","doi":"10.1016/j.survophthal.2025.06.009","DOIUrl":"10.1016/j.survophthal.2025.06.009","url":null,"abstract":"<div><div>Giant cell arteritis (GCA) is an autoimmune disease of medium and large sized vessels. It is the most prevalent form of primary vasculitis in the western world. Vascular inflammation in GCA can lead to vascular occlusion. Severe neuro-ophthalmological complications, such as arteritic anterior ischemic optic neuropathy (AAION), may present with sudden partial or complete vision loss or diplopia. Visual impairment is often refractory to corticosteroid therapy, underscoring the critical importance of early diagnosis. Delayed diagnosis and initiation of high-dose corticosteroids can lead to contralateral eye involvement and bilateral irreversible vision loss. Recent advances in expedited diagnostics have significantly improved outcomes in GCA patients, particularly by reducing ischemic neuro-ophthalmological events. Thus, a key factor has been the introduction of Fast-Track Clinics that have successfully decreased the incidence of permanent blindness in GCA patients. In these clinics, imaging modalities such as vascular ultrasound, magnetic resonance imaging, and positron emission tomography-computed tomography play a critical role in both diagnosis and disease monitoring, enabling timely and accurate intervention. On the therapeutic front, cytokine-specific inhibitors have improved GCA management, enhancing remission rates and reducing glucocorticoid use. Tocilizumab, an IL-6 receptor (IL-6R) inhibitor, has become a cornerstone of GCA treatment; however, since some patients do not respond to IL-6R inhibition, ongoing research is exploring alternative disease-modifying therapies. These new approaches aim to reduce glucocorticoid dependency, mitigate side effects, enhance visual outcomes, and improve patient outcomes, highlighting a shift towards more individualized treatment approaches.</div></div>","PeriodicalId":22102,"journal":{"name":"Survey of ophthalmology","volume":"71 2","pages":"Pages 483-497"},"PeriodicalIF":5.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144337015","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-03-01Epub Date: 2025-10-01DOI: 10.1016/j.survophthal.2025.09.023
Yong Liu , Di Gong , Kuanrong Dang , Junhong Guo , Zhichao Yan , Xiaoli Shen , Jiantao Wang
Our study aims to assess the utility of various next-generation sequencing (NGS) technologies and explore their role in primary glaucoma genetic research. We conducted a systematic review as of January 19, 2025, using PubMed, Scopus, and Web of Science, with study quality evaluated using the QUADAS-2 checklist. We assessed the diagnostic rates of various NGS technologies across different glaucoma subtypes. The study protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO: CRD42024614663). We included 19 studies utilizing whole exome sequencing (WES), whole genome sequencing (WGS), and panel sequencing for assessing genetic features in primary angle-closure glaucoma (PACG), primary congenital glaucoma (PCG), primary open-angle glaucoma (POAG), and juvenile open-angle glaucoma (JOAG). The overall diagnostic rate of NGS technologies was 26.2 % (95 % CI: 15.9 %-36.5 %). WES showed superior performance in PCG (46.7 %), POAG (8.9 %), and JOAG (12.4 %), while panel sequencing achieved a higher rate in PACG (56.4 %). Subtype-specific genes included CYP1B1 in PCG, MYOC in JOAG, and WDR36 in POAG/PACG. Notably, all CYP1B1 gene variant loci are concentrated in 2 specific regions on chromosome 2. This study underscores the significance of NGS in primary glaucoma genetic research, advocating for subtype-specific sequencing strategies to facilitate precise diagnosis and treatment.
{"title":"Diagnostic accuracy of next generation sequencing-based genetic research for primary glaucoma: A systematic review and meta-analysis","authors":"Yong Liu , Di Gong , Kuanrong Dang , Junhong Guo , Zhichao Yan , Xiaoli Shen , Jiantao Wang","doi":"10.1016/j.survophthal.2025.09.023","DOIUrl":"10.1016/j.survophthal.2025.09.023","url":null,"abstract":"<div><div>Our study aims to assess the utility of various next-generation sequencing (NGS) technologies and explore their role in primary glaucoma genetic research. We conducted a systematic review as of January 19, 2025, using PubMed, Scopus, and Web of Science, with study quality evaluated using the QUADAS-2 checklist. We assessed the diagnostic rates of various NGS technologies across different glaucoma subtypes. The study protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO: CRD42024614663). We included 19 studies utilizing whole exome sequencing (WES), whole genome sequencing (WGS), and panel sequencing for assessing genetic features in primary angle-closure glaucoma (PACG), primary congenital glaucoma (PCG), primary open-angle glaucoma (POAG), and juvenile open-angle glaucoma (JOAG). The overall diagnostic rate of NGS technologies was 26.2 % (95 % CI: 15.9 %-36.5 %). WES showed superior performance in PCG (46.7 %), POAG (8.9 %), and JOAG (12.4 %), while panel sequencing achieved a higher rate in PACG (56.4 %). Subtype-specific genes included <em>CYP1B1</em> in PCG, <em>MYOC</em> in JOAG, and <em>WDR36</em> in POAG/PACG. Notably, all <em>CYP1B1</em> gene variant loci are concentrated in 2 specific regions on chromosome 2. This study underscores the significance of NGS in primary glaucoma genetic research, advocating for subtype-specific sequencing strategies to facilitate precise diagnosis and treatment.</div></div>","PeriodicalId":22102,"journal":{"name":"Survey of ophthalmology","volume":"71 2","pages":"Pages 498-511"},"PeriodicalIF":5.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145226011","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-03-01Epub Date: 2025-07-21DOI: 10.1016/j.survophthal.2025.07.005
Michael Drakopoulos MD,MPhil, Arnold Nadel MD, Harnaina K. Bains MD, Jay B. Bisen BS, Hayden Sikora BA, Kevin X. Zhang MD, PhD, Alessandro Marchese MD, Joseph Fahey MS, Rukhsana G. Mirza MD,MS
Optical coherence tomography angiography (OCTA) noninvasively and quantitatively images the microvasculature of the eye’s posterior segment in 3 dimensions. OCTA has known utility in the diagnosis and management of certain ocular conditions and is now being used to assess systemic conditions, including respiratory, cardiovascular, renal, obstetric, neurologic, rheumatologic, and genetic conditions, among others. OCTA may improve our understanding of the pathophysiology of systemic conditions and identify biomarkers useful in their diagnosis, prognosis, and management. We detail known associations between quantitative retinal, optic nerve head, and choriocapillaris OCTA findings and clinically relevant features of systemic conditions, including laboratory markers and disease severity and prognosis. We find that the breadth and depth of such correlations solidify OCTA’s role in the emerging field of oculomics, which seeks to identify ocular imaging biomarkers for use in the study and management of nonocular conditions.
{"title":"Quantitative ophthalmic posterior segment optical coherence tomography angiography and systemic conditions","authors":"Michael Drakopoulos MD,MPhil, Arnold Nadel MD, Harnaina K. Bains MD, Jay B. Bisen BS, Hayden Sikora BA, Kevin X. Zhang MD, PhD, Alessandro Marchese MD, Joseph Fahey MS, Rukhsana G. Mirza MD,MS","doi":"10.1016/j.survophthal.2025.07.005","DOIUrl":"10.1016/j.survophthal.2025.07.005","url":null,"abstract":"<div><div>Optical coherence tomography angiography (OCTA) noninvasively and quantitatively images the microvasculature of the eye’s posterior segment in 3 dimensions. OCTA has known utility in the diagnosis and management of certain ocular conditions and is now being used to assess systemic conditions, including respiratory, cardiovascular, renal, obstetric, neurologic, rheumatologic, and genetic conditions, among others. OCTA may improve our understanding of the pathophysiology of systemic conditions and identify biomarkers useful in their diagnosis, prognosis, and management. We detail known associations between quantitative retinal, optic nerve head, and choriocapillaris OCTA findings and clinically relevant features of systemic conditions, including laboratory markers and disease severity and prognosis. We find that the breadth and depth of such correlations solidify OCTA’s role in the emerging field of oculomics, which seeks to identify ocular imaging biomarkers for use in the study and management of nonocular conditions.</div></div>","PeriodicalId":22102,"journal":{"name":"Survey of ophthalmology","volume":"71 2","pages":"Pages 423-455"},"PeriodicalIF":5.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144699572","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-03-01Epub Date: 2025-07-22DOI: 10.1016/j.survophthal.2025.07.009
Claire Y. Hooper FRANZCO , Lisia Barros Ferreira MD, PhD , Anagha Vaze FRANZCO, MPhil , Daniel V. Vasconcelos-Santos MD, PhD , Debra A. Goldstein MD , Demi Gertig MOpt , Justine R. Smith FRANZCO, PhD
Relentless placoid chorioretinitis (RPC) is a rare, vision-threatening posterior uveitis that predominantly affects young adults. The hallmark clinical findings are numerous scattered placoid chorioretinal lesions involving the midperipheral and far peripheral fundus as well as the posterior pole and a persistent or recurrent course resulting in lesions at different chronological stages, with fresh creamy placoid lesions and healing pigmented lesions being present at the same time. Although RPC is frequently described as a disease that is intermediate between acute posterior multifocal placoid pigment epitheliopathy (APMPPE) and serpiginous choroiditis, it more closely resembles APMPPE. It is important to identify those patients with RPC who present with an APMPPE phenotype so that appropriate immunomodulatory therapy is instituted without delay, as most cases of RPC are refractory to corticosteroid monotherapy. Examination findings may help differentiate RPC and APMPPE. Multimodal imaging, including ultra-widefield imaging, and selective investigations aid in distinguishing RPC from other placoid diseases and types of posterior uveitis.
{"title":"Relentless placoid chorioretinitis","authors":"Claire Y. Hooper FRANZCO , Lisia Barros Ferreira MD, PhD , Anagha Vaze FRANZCO, MPhil , Daniel V. Vasconcelos-Santos MD, PhD , Debra A. Goldstein MD , Demi Gertig MOpt , Justine R. Smith FRANZCO, PhD","doi":"10.1016/j.survophthal.2025.07.009","DOIUrl":"10.1016/j.survophthal.2025.07.009","url":null,"abstract":"<div><div>Relentless placoid chorioretinitis (RPC) is a rare, vision-threatening posterior uveitis that predominantly affects young adults. The hallmark clinical findings are numerous scattered placoid chorioretinal lesions involving the midperipheral and far peripheral fundus as well as the posterior pole and a persistent or recurrent course resulting in lesions at different chronological stages, with fresh creamy placoid lesions and healing pigmented lesions being present at the same time. Although RPC is frequently described as a disease that is intermediate between acute posterior multifocal placoid pigment epitheliopathy (APMPPE) and serpiginous choroiditis, it more closely resembles APMPPE. It is important to identify those patients with RPC who present with an APMPPE phenotype so that appropriate immunomodulatory therapy is instituted without delay, as most cases of RPC are refractory to corticosteroid monotherapy. Examination findings may help differentiate RPC and APMPPE. Multimodal imaging, including ultra-widefield imaging, and selective investigations aid in distinguishing RPC from other placoid diseases and types of posterior uveitis.</div></div>","PeriodicalId":22102,"journal":{"name":"Survey of ophthalmology","volume":"71 2","pages":"Pages 467-482"},"PeriodicalIF":5.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144708770","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-03-01Epub Date: 2025-06-11DOI: 10.1016/j.survophthal.2025.06.004
Bassel Hammoud , Justin S. Schumacher , Hongyuan Zhang , Barbara A.L. Dutra , Bianca N. Susanna , Giuliano Scarcelli , J. Bradley Randleman
Corneal mechanical weakness is widely recognized as the root cause of keratoconus and a primary driver for undesirable refractive surgery outcomes. Theory, finite element modeling, and initial data predict that focal rather than generalized weakening precipitates corneal mechanical decompensation. Direct, 3-dimensionally (3-D) localized in vivo corneal mechanical measurements thus have the potential to revolutionize keratoconus management and the surgical correction of myopia. Collagen microarchitecture and mechanical profiles in normal and keratoconic corneas have been evaluated ex vivo, but significant gaps remain in our understanding of the earliest subclinical manifestations that can eventually lead to clinical disease. Nonperturbative Brillouin microscopy has emerged as a novel approach for measuring corneal mechanics by analyzing Brillouin light scattering, which encodes the corneal elastic modulus (longitudinal modulus). Early ex vivo works demonstrated the technique’s ability to identify depth-dependent (axial) anisotropy in the normal cornea, focal weakening in the keratoconic cornea, and stiffening after corneal cross-linking. Recent advances using motion-tracking Brillouin imaging, which employs optical coherence tomography and eye tracking to facilitate 3-D signal localization, have provided novel insights into keratoconus at the subclinical stage. Locally reduced Brillouin shift values in the anterior cornea have differentiated subclinical keratoconic cornea from normal controls and outperformed current clinical standard morphologic evaluation using Scheimpflug technology. Herein, we highlight the development of Brillouin microscopy for in vivo corneal analysis, current imaging advances and technological limitations, and future directions for in vivo analysis of subclinical keratoconus to advance our understanding of keratoconus diagnosis, disease evolution, and management.
{"title":"Brillouin microscopy for focal biomechanical measurements in normal and keratoconic corneas: A narrative review","authors":"Bassel Hammoud , Justin S. Schumacher , Hongyuan Zhang , Barbara A.L. Dutra , Bianca N. Susanna , Giuliano Scarcelli , J. Bradley Randleman","doi":"10.1016/j.survophthal.2025.06.004","DOIUrl":"10.1016/j.survophthal.2025.06.004","url":null,"abstract":"<div><div>Corneal mechanical weakness is widely recognized as the root cause of keratoconus and a primary driver for undesirable refractive surgery outcomes. Theory, finite element modeling, and initial data predict that focal rather than generalized weakening precipitates corneal mechanical decompensation. Direct, 3-dimensionally (3-D) localized <em>in vivo</em> corneal mechanical measurements thus have the potential to revolutionize keratoconus management and the surgical correction of myopia. Collagen microarchitecture and mechanical profiles in normal and keratoconic corneas have been evaluated <em>ex vivo</em>, but significant gaps remain in our understanding of the earliest subclinical manifestations that can eventually lead to clinical disease. Nonperturbative Brillouin microscopy has emerged as a novel approach for measuring corneal mechanics by analyzing Brillouin light scattering, which encodes the corneal elastic modulus (longitudinal modulus). Early <em>ex vivo</em> works demonstrated the technique’s ability to identify depth-dependent (axial) anisotropy in the normal cornea, focal weakening in the keratoconic cornea, and stiffening after corneal cross-linking. Recent advances using motion-tracking Brillouin imaging, which employs optical coherence tomography and eye tracking to facilitate 3-D signal localization, have provided novel insights into keratoconus at the subclinical stage. Locally reduced Brillouin shift values in the anterior cornea have differentiated subclinical keratoconic cornea from normal controls and outperformed current clinical standard morphologic evaluation using Scheimpflug technology. Herein, we highlight the development of Brillouin microscopy for <em>in vivo</em> corneal analysis, current imaging advances and technological limitations, and future directions for in vivo analysis of subclinical keratoconus to advance our understanding of keratoconus diagnosis, disease evolution, and management.</div></div>","PeriodicalId":22102,"journal":{"name":"Survey of ophthalmology","volume":"71 2","pages":"Pages 662-673"},"PeriodicalIF":5.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144294955","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-03-01Epub Date: 2025-10-02DOI: 10.1016/j.survophthal.2025.09.019
David A. Merle MD , Federico Beretta , Riccardo Sacconi , Giuseppe Querques
Age-related macular degeneration (AMD) remains among the leading causes of blindness in industrialized nations, with fibrosis secondary to macular neovascularization (MNV) significantly contributing to visual decline despite treatment with anti-vascular endothelial growth factor therapy. Although traditionally viewed as detrimental, fibrosis may reflect a delicate balance between beneficial vessel stabilization and harmful scarring. We critically evaluate the pathophysiology of fibrosis in AMD and introduces the novel hypothetical concept of “fibrogliosis”, which emphasizes the central role of Müller glia and retinal microglia activation following disruption of the outer blood-retinal barrier. According to this concept, fibrogliosis manifests differently among MNV subtypes, influenced largely by their impact on outer blood-retinal barrier integrity. Recognizing this variability underscores the importance of further investigation into the hypothetical concept of fibrogliosis, which in theory could guide future therapeutic strategies to balance vascular stabilization with the modulation of neovascularization and fibrosis.
{"title":"Fibrogliosis in neovascular age-related macular degeneration: A new mechanistic perspective","authors":"David A. Merle MD , Federico Beretta , Riccardo Sacconi , Giuseppe Querques","doi":"10.1016/j.survophthal.2025.09.019","DOIUrl":"10.1016/j.survophthal.2025.09.019","url":null,"abstract":"<div><div>Age-related macular degeneration (AMD) remains among the leading causes of blindness in industrialized nations, with fibrosis secondary to macular neovascularization (MNV) significantly contributing to visual decline despite treatment with anti-vascular endothelial growth factor therapy. Although traditionally viewed as detrimental, fibrosis may reflect a delicate balance between beneficial vessel stabilization and harmful scarring. We critically evaluate the pathophysiology of fibrosis in AMD and introduces the novel hypothetical concept of “fibrogliosis”, which emphasizes the central role of Müller glia and retinal microglia activation following disruption of the outer blood-retinal barrier. According to this concept, fibrogliosis manifests differently among MNV subtypes, influenced largely by their impact on outer blood-retinal barrier integrity. Recognizing this variability underscores the importance of further investigation into the hypothetical concept of fibrogliosis, which in theory could guide future therapeutic strategies to balance vascular stabilization with the modulation of neovascularization and fibrosis.</div></div>","PeriodicalId":22102,"journal":{"name":"Survey of ophthalmology","volume":"71 2","pages":"Pages 334-345"},"PeriodicalIF":5.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145225987","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-03-01Epub Date: 2025-09-17DOI: 10.1016/j.survophthal.2025.09.012
Antonio La Rosa MD , Alessandro Feo MD , Elodie Bousquet MD PhD , Diogo Cabral MD , Yousef Fouad MD , Mariacristina Parravano MD , Mario R. Romano MD PhD
Angioid streaks-related choroidal neovascularization (AS-CNV) is a vision-threatening complication arising from breaks in a calcified Bruch membrane, commonly associated with systemic conditions such as pseudoxanthoma elasticum (PXE). This review comprehensively addresses the clinical features of AS-CNV, emphasizing its distinct pathophysiology and systemic implications. We highlight the critical role of multimodal imaging—including color fundus photography, fundus autofluorescence, fluorescein and indocyanine green angiography, spectral-domain optical coherence tomography, and optical coherence tomography angiography—in accurately diagnosing and differentiating AS-CNV from other choroidal neovascular pathologies. The integration of imaging biomarkers and vascular pattern analysis facilitates early detection of subclinical and quiescent CNV, allowing for timely, individualized anti- vascular endothelial growth facgtor therapy. Additionally, the systemic management of PXE and its cardiovascular, renal, and gastrointestinal manifestations is underscored to optimize overall patient outcomes. We provide an up-to-date synthesis of diagnostic advances and treatment strategies aimed at improving visual prognosis in patients with AS-CNV.
{"title":"Angioid streaks-related choroidal neovascularization: Clinical features, multimodal imaging-based differential diagnosis, and optimized treatment strategies","authors":"Antonio La Rosa MD , Alessandro Feo MD , Elodie Bousquet MD PhD , Diogo Cabral MD , Yousef Fouad MD , Mariacristina Parravano MD , Mario R. Romano MD PhD","doi":"10.1016/j.survophthal.2025.09.012","DOIUrl":"10.1016/j.survophthal.2025.09.012","url":null,"abstract":"<div><div>Angioid streaks-related choroidal neovascularization (AS-CNV) is a vision-threatening complication arising from breaks in a calcified Bruch membrane, commonly associated with systemic conditions such as pseudoxanthoma elasticum (PXE). This review comprehensively addresses the clinical features of AS-CNV, emphasizing its distinct pathophysiology and systemic implications. We highlight the critical role of multimodal imaging—including color fundus photography, fundus autofluorescence, fluorescein and indocyanine green angiography, spectral-domain optical coherence tomography, and optical coherence tomography angiography—in accurately diagnosing and differentiating AS-CNV from other choroidal neovascular pathologies. The integration of imaging biomarkers and vascular pattern analysis facilitates early detection of subclinical and quiescent CNV, allowing for timely, individualized anti- vascular endothelial growth facgtor therapy. Additionally, the systemic management of PXE and its cardiovascular, renal, and gastrointestinal manifestations is underscored to optimize overall patient outcomes. We provide an up-to-date synthesis of diagnostic advances and treatment strategies aimed at improving visual prognosis in patients with AS-CNV.</div></div>","PeriodicalId":22102,"journal":{"name":"Survey of ophthalmology","volume":"71 2","pages":"Pages 309-320"},"PeriodicalIF":5.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145092574","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}