Min Seok Kim, Soo Hyun Choi, Hyun Young Park, Sun Young Jang, JaeSang Ko, Jae-Woo Kim, Jin Sook Yoon
{"title":"Role of SerpinA3 in the Pathogenesis of Graves' Orbitopathy in Orbital Fibroblasts.","authors":"Min Seok Kim, Soo Hyun Choi, Hyun Young Park, Sun Young Jang, JaeSang Ko, Jae-Woo Kim, Jin Sook Yoon","doi":"10.1167/iovs.66.4.20","DOIUrl":"https://doi.org/10.1167/iovs.66.4.20","url":null,"abstract":"<p><strong>Purpose: </strong>We investigated the implications of SerpinA3, a secretory serine protease inhibitor, in inflammation and adipogenesis of Graves' orbitopathy (GO). To identify its precise function in GO pathogenesis, we evaluated the role of SerpinA3 in the inflammation and adipogenesis of GO.</p><p><strong>Methods: </strong>SerpinA3 expression was compared between GO (n = 30) and normal participants (n = 28) in orbital tissue explants using real-time PCR. Orbital fibroblasts from GO (n = 3) and normal participants (n = 3) were transfected with or without small interfering RNA against SerpinA3 before IL-1β stimulation. Western blotting assessed inflammatory cytokine and signaling molecule expression. Adipogenic differentiation was assessed using Oil Red O staining, and adipogenic marker expression was determined through Western blotting. Enzyme-linked immunosorbent assay was used to compare prostaglandin E2 (PGE2) and hyaluronan levels in GO (n = 4) and normal participants (n = 3).</p><p><strong>Results: </strong>SerpinA3 transcript levels were significantly higher in GO orbital tissues. Silencing SerpinA3 suppressed the IL-1β-induced expression of IL-6, IL-8, monocyte chemotactic protein 1, intercellular adhesion molecule 1, cyclooxygenase 2, and PGE2 and attenuated the levels of phosphorylated nuclear factor κB, Akt, extracellular signal-regulated kinase, p38, and c-Jun N-terminal kinase. Moreover, silencing SerpinA3 reduced hyaluronan production, adipogenic differentiation, and adipogenic marker expression, including peroxisome proliferator-activated receptor-γ, CCAAT/enhancer-binding proteins α and β, adipocyte protein 2, adiponectin, and leptin.</p><p><strong>Conclusions: </strong>Silencing SerpinA3 attenuated the expression of proinflammatory mediators, adipogenic differentiation, and hyaluronan production. Our results indicate that SerpinA3 plays a significant role in GO and may serve as a novel therapeutic target.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 4","pages":"20"},"PeriodicalIF":5.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143811340","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}
Sebastiano Giallongo, Francesco Bellia, Andrea Russo, Matteo Fallico, Riccardo Polosa, Niccolò Castellino, Antonio Longo, Rosalia Emma, Konstantinos Partsinevelos, Massimo Caruso, Arief S Kartasasmita, Giuseppe Sferrazzo, Ignazio Alberto Barbagallo, Rosario Caltabiano, Giuseppe Broggi, Amer M Alanazi, Giovanni Li Volti
{"title":"Comparative Evaluation of Cigarette Smoke and a Heated Tobacco Product on Corneal Oxidative Stress in an Air/Liquid Interface Model.","authors":"Sebastiano Giallongo, Francesco Bellia, Andrea Russo, Matteo Fallico, Riccardo Polosa, Niccolò Castellino, Antonio Longo, Rosalia Emma, Konstantinos Partsinevelos, Massimo Caruso, Arief S Kartasasmita, Giuseppe Sferrazzo, Ignazio Alberto Barbagallo, Rosario Caltabiano, Giuseppe Broggi, Amer M Alanazi, Giovanni Li Volti","doi":"10.1167/iovs.66.4.4","DOIUrl":"10.1167/iovs.66.4.4","url":null,"abstract":"<p><strong>Purpose: </strong>Tobacco smoke harbors toxic combustion by-products contributing to inflammatory diseases. Cigarette smoke's impact on ocular diseases has been poorly characterized, despite conjunctival mucosa's sensitivity to these toxicants. Of note, cigarette smoke triggers redness, tearing, and discomfort, accounting as a risk factor for glaucoma, macular degeneration, cataracts, and other eye conditions. Low quit rates of cessation highlight the need for alternatives. Heated tobacco products (HTPs), may represent a less toxic alternative for those smokers. This study evaluates cigarette smoke and HTPs effects on cornea under standard and clinically relevant conditions.</p><p><strong>Methods: </strong>Corneal tissues collected from donors and in vitro model in two different cell lines of corneal epithelium were exposed to cigarette (1R6F) smoke and HTPs vapor. Air exposure was included as a control. Tissue pathological evaluation was carried out by hematoxylin and eosin staining. Reactive oxygen species (ROS) were measured, and quantitative PCR assessed inflammatory and antioxidant genes expression. Proteome analysis was used to evaluate differentially expressed proteins related to the oxidative stress. Scratch assay measured smoke and HTPs impact on cells.</p><p><strong>Results: </strong>Hematoxylin & eosin staining highlighted that cigarette smoke impairs corneal tissue integrity, leading to ROS accumulation and inflammation, as proved by qPCR analysis. Proteomic analysis showed that corneal tissue's proteins were differently oxidized by the different experimental conditions. HTP targeted structural intracellular proteins, whereas 1R6F affects different members of collagen family. Finally, cigarette smoke, but not HTPs, impairs epithelial cells wound closure.</p><p><strong>Conclusions: </strong>Smoking increases oxidative stress, leading to significant corneal damage and inflammation. HTPs may offer a less toxic alternative.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 4","pages":"4"},"PeriodicalIF":5.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11968005/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143763952","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Caili Hao, Emily Fan, Zongbo Wei, Kazi Rafsan Radeen, Neha Purohit, Kailin Li, Sharad Purohit, Xingjun Fan
{"title":"Elevated Inflammatory Cytokines Persist in the Aqueous Humor Years After Cataract Surgery.","authors":"Caili Hao, Emily Fan, Zongbo Wei, Kazi Rafsan Radeen, Neha Purohit, Kailin Li, Sharad Purohit, Xingjun Fan","doi":"10.1167/iovs.66.4.12","DOIUrl":"10.1167/iovs.66.4.12","url":null,"abstract":"<p><strong>Purpose: </strong>There is currently limited information regarding inflammation and cytokine levels in the aqueous humor (AH) of adult patients with cataract who have undergone phacoemulsification cataract extraction without other ocular comorbidities.</p><p><strong>Methods: </strong>AH samples were collected from healthy, non-surgical donors and donors with a history of cataract surgery performed 3 to 12 years prior. Sixty-three cytokines and growth factors were measured using bead-based ProcartaPlex immunoassays. Data analysis included normal distribution assessment, pairwise correlation, logistic regression, and ridge regression.</p><p><strong>Results: </strong>Of the 63 molecules analyzed, 34 were selected for further study. Cytokines, such as CD40L, IL-7, MIP-1α, and LIF, were found at significantly higher concentrations in AH samples from donors with a history of cataract surgery compared with non-cataract controls. In contrast, lower concentrations of IL-23, TRAIL, IL-12p70, IFNγ, MIP-3α, and SCF were observed in post-surgical samples. Pairwise correlation analysis identified clusters of significantly correlated molecules, suggesting their potential involvement in the inflammatory environment of AH post-cataract surgery. AH concentration of 34 proteins was combined into a post-cataract surgery inflammation index (PCSII) using ridge regression, which differs significantly between post-cataract surgery donors and non-cataract controls. This PCSII shows that any increase in AH levels of these molecules can stratify cataract surgery donors into low and high-risk of inflammatory groups.</p><p><strong>Conclusions: </strong>This study indicates that cataract surgery may lead to a chronic inflammatory state in the AH, which can persist for extended periods post-surgery.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 4","pages":"12"},"PeriodicalIF":5.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143780013","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}
{"title":"CD4+CD25- T-Cell-Secreted IFN-γ Promotes Corneal Nerve Degeneration in Diabetic Mice.","authors":"Yujing Lin, Lingling Yang, Ya Li, Shengqian Dou, Zhenzhen Zhang, Qingjun Zhou","doi":"10.1167/iovs.66.4.15","DOIUrl":"https://doi.org/10.1167/iovs.66.4.15","url":null,"abstract":"<p><strong>Purpose: </strong>This study aimed to explore the relationship between corneal nerve degeneration and elevated dendritic cells (DCs) in diabetic keratopathy.</p><p><strong>Methods: </strong>Corneas from diabetic and healthy mice were analyzed using single-cell RNA sequencing. Corneal nerve density and DC and T-cell infiltration were quantified through whole-mount corneal staining. Freshly isolated mouse trigeminal ganglion (TG) neurons were co-cultured with immature DCs, mature DCs, activated CD8+ T cells, and CD4+CD25- T cells. TG neurite outgrowth was assessed to identify potential effector cells driving corneal nerve degeneration. In addition, interferon-gamma (IFN-γ) and blocking antibodies were used to evaluate their effects on TG neurite outgrowth and corneal nerve degeneration in mice.</p><p><strong>Results: </strong>Compared with age-matched healthy mice, diabetic mice exhibited a significant reduction in corneal nerve density and sensitivity, along with increased infiltration of DCs, CD4+ T cells, and CD8+ T cells. In vitro co-culture experiments revealed that CD4+CD25- T cells, rather than DCs and CD8+ T cells, significantly inhibited TG neurite outgrowth. Among cytokines, elevated IFN-γ in diabetic corneas impaired TG neurite outgrowth and induced corneal nerve degeneration, whereas IL-4 and IL-17 had no such effect. Blocking IFN-γ alleviated CD4+CD25- T-cell-induced inhibition of TG neurite outgrowth and corneal nerve degeneration in diabetic mice.</p><p><strong>Conclusions: </strong>CD4+CD25- T cells, but not DCs or CD8+ T cells, contribute to corneal nerve degeneration in diabetic mice, a process partially mediated by IFN-γ.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 4","pages":"15"},"PeriodicalIF":5.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143795504","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}
Le Chang, Fen Song, Shijia Qu, Huazheng Cao, Yanan Wu, Lulu Xu, Jing Wang, Ruirui Zhang, Chao Xue, Yan Wang
{"title":"In Vivo Brillouin Analysis of Lens Nucleus and Cortex in Adult Myopic Eyes and Their Correlation With Accommodation.","authors":"Le Chang, Fen Song, Shijia Qu, Huazheng Cao, Yanan Wu, Lulu Xu, Jing Wang, Ruirui Zhang, Chao Xue, Yan Wang","doi":"10.1167/iovs.66.4.6","DOIUrl":"10.1167/iovs.66.4.6","url":null,"abstract":"<p><strong>Purpose: </strong>The purpose of this study was to investigate the in vivo biomechanical properties of crystalline lens nucleus and cortex in adults with myopia, their potential influences, and the correlation between these properties and ocular accommodation.</p><p><strong>Methods: </strong>The study included 195 right eyes of 195 participants, divided into 4 groups based on spherical equivalent: emmetropia (37 eyes), low myopia (41 eyes), moderate myopia (59 eyes), and high myopia (58 eyes). Participants underwent comprehensive ophthalmological examinations, including intraocular pressure, axial length, cycloplegic refraction, lens morphology, accommodation measurements, and Brillouin optical scanning of the lens. Additionally, demographic information, such as age and sex, was recorded. Normality tests were performed on the data using the Kolmogorov-Smirnov test. Between-group differences were examined using the Kruskal-Wallis test. Correlation and multiple regression analyses were conducted to analyze the factors associated with lens biomechanical properties and accommodation.</p><p><strong>Results: </strong>The mean longitudinal modulus of the crystalline lens nucleus (LMN), anterior cortex (LMAC), and posterior cortex (LMPC) was 3.395 ± 0.027 GPa, 3.030 ± 0.066 GPa, and 2.990 ± 0.066 GPa, respectively, in adult myopia and 3.342 ± 0.024 GPa, 3.015 ± 0.0488 GPa, and 2.978 ± 0.049 GPa, respectively, in emmetropia. LMN was significantly higher in myopia (difference = 0.047, 95% confidence interval [CI] = 0.037 to 0.057, P < 0.001) and increased significantly with higher degrees of myopia (standardized β = -0.712, P < 0.001). No statistical differences in the LMAC or LMPC were observed between myopia and emmetropia. Lens densitometry on the centerline was the only lens parameter independently correlated with LMN (standardized β = -0.282, P < 0.01). Increased LMN in myopia was independently correlated with increased amplitude of accommodation (AMP) and decreased accommodative facility (AF; standardized β = 0.198, -0.237, all P < 0.05).</p><p><strong>Conclusions: </strong>LMN was significantly higher in adult patients with myopia than in emmetropia and increased with increasing myopia. Increased LMN in myopia significantly correlated with decreased AF and increased AMP. High LMN may be an important biological alteration during the development of adult myopia, especially high myopia, providing new insights into myopia pathogenesis.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 4","pages":"6"},"PeriodicalIF":5.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11968000/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143763173","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Suguru Ito, Yuki Oyama, Taichi Yuasa, Koki Amano, Kotaro Onishi, Ayaka Izumi, Albert S Jun, Masahito Ikawa, Noriko Koizumi, Naoki Okumura
{"title":"Heterozygous Tcf4 Deficiency Mitigates Fuchs Endothelial Corneal Dystrophy Progression in a Mouse Model.","authors":"Suguru Ito, Yuki Oyama, Taichi Yuasa, Koki Amano, Kotaro Onishi, Ayaka Izumi, Albert S Jun, Masahito Ikawa, Noriko Koizumi, Naoki Okumura","doi":"10.1167/iovs.66.4.19","DOIUrl":"10.1167/iovs.66.4.19","url":null,"abstract":"<p><strong>Purpose: </strong>The purpose of this study was to use Col8a2Q455K/Q455K mice, an established Fuchs endothelial corneal dystrophy (FECD) model, to investigate whether heterozygous knockout of Tcf4 expression could ameliorate the progression of FECD.</p><p><strong>Methods: </strong>Tcf4 heterozygous knockout mice were generated using CRISPR/Cas9-mediated deletion of exons 2 and 3. These mice were crossed with Col8a2Q455K/Q455K mice to obtain Col8a2Q455K/Q455K/Tcf4± mice. Differential gene expression profiles in corneal endothelial cells of Col8a2Q455K/Q455K/Tcf4± and Col8a2Q455K/Q455K mice were then examined using RNA sequencing. Guttae formation and corneal endothelial cell density were assessed using contact specular microscopy. Expression of extracellular matrix (ECM) components was evaluated by qPCR and immunofluorescence analysis.</p><p><strong>Results: </strong>RNA-Seq analysis revealed 1053 differentially expressed genes between the Col8a2Q455K/Q455K/Tcf4± and the Col8a2Q455K/Q455K mice, with significant enrichment in ion channel-related pathways and downregulation of TNF-associated signaling pathways. Contact specular microscopy in 28-week-old mice demonstrated that guttae formation was significantly lower in the Col8a2Q455K/Q455K/Tcf4± mice than in the Col8a2Q455K/Q455K mice (0.71 ± 0.77% vs. 1.87 ± 1.43%, P < 0.001), whereas the corneal endothelial cell density was higher (1819 ± 170 vs. 1521 ± 292 cells/mm², P < 0.001). ECM components-particularly fibronectin and type I collagen, which are major constituents of guttae-were significantly decreased in the Col8a2Q455K/Q455K/Tcf4± mice.</p><p><strong>Conclusions: </strong>Heterozygous knockout of Tcf4 significantly suppressed the progression of the FECD phenotype, including guttae formation and endothelial cell loss, in the FECD mouse model. These findings provide in vivo support for TCF4 as a potential therapeutic target for FECD treatment.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 4","pages":"19"},"PeriodicalIF":5.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143803244","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}
Janice X Ong, Hunter J Lee, Nicole L Decker, Daniela Castellanos-Canales, Hisashi Fukuyama, Amani A Fawzi
{"title":"Volumetric Measures of Capillary Nonperfusion on Optical Coherence Tomography Angiography Detect Early Ischemia in Diabetes Without Retinopathy.","authors":"Janice X Ong, Hunter J Lee, Nicole L Decker, Daniela Castellanos-Canales, Hisashi Fukuyama, Amani A Fawzi","doi":"10.1167/iovs.66.4.2","DOIUrl":"10.1167/iovs.66.4.2","url":null,"abstract":"<p><strong>Purpose: </strong>The purpose of this study was to compare volumetric 3-dimensional (3D) against standard 2-dimensional (2D) measurements of ischemia for distinguishing early stages of diabetic retinopathy (DR) using optical coherence tomography angiography (OCTA).</p><p><strong>Methods: </strong>This cross-sectional study considered 82 eyes of 82 patients (aged 51.0 ± 11.9 years) including 27 healthy controls, 31 patients with diabetes mellitus (DM) without DR, and 24 patients with mild nonproliferative DR (NPDR). Using OCTA, we obtained 2D scans and 3D volumes of the superficial capillary plexus (SCP), middle capillary plexus (MCP), and deep capillary plexus (DCP). We calculated geometric perfusion deficits (GPDs), which define ischemic regions as those located farther than a specified threshold distance from the nearest blood vessel. For the GPD parameter, we compared the performance of a 20 µm versus 30 µm cutoff.</p><p><strong>Results: </strong>On 2D scans, eyes with mild NPDR had significantly higher GPDs in all 3 retinal capillary layers, indicating worse ischemia, compared with both healthy controls and patients with DM without DR, using either threshold (20 µm or 30 µm) to define GPD (all P < 0.05). DM without DR showed no significant difference from healthy eyes in 2D images. Interestingly, however, using 3D volumes, DM without DR eyes had significantly greater DCP GPDs than healthy eyes using a GPD threshold of 20 µm (P = 0.012), but not with 30 µm (P = 0.057).</p><p><strong>Conclusions: </strong>Using a stringent threshold (20 µm), volumetric OCTA imaging detects significant DCP perfusion defects in diabetic eyes even before DR onset, whereas traditional 2D OCTA does not. Volumetric scans may therefore be more sensitive to early ischemia in diabetes.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 4","pages":"2"},"PeriodicalIF":5.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11968003/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143763420","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Temporal Frequency Modulation of Binocular Balance in Normal and Amblyopic Vision.","authors":"Chenyan Zhou, Jiawei Zhou, Seung Hyun Min","doi":"10.1167/iovs.66.4.8","DOIUrl":"10.1167/iovs.66.4.8","url":null,"abstract":"<p><strong>Purpose: </strong>To investigate how temporal frequency modulates binocular balance in normally sighted and amblyopic adults.</p><p><strong>Methods: </strong>Twenty-three controls and 13 amblyopes participated in this study. The effects of temporal frequency differences and monocularly directed attention on binocular balance were measured using an onset binocular rivalry task with sinusoidally flickering gratings at varying temporal frequencies and static gratings with monocular attentional cues. For the flickering gratings, different combinations of temporal frequencies (2, 4, or 10 Hz in one eye vs. 2, 3, 4, 6, 10, 15, or 20 Hz in the other) were presented. Their effects were then compared, and their relationship was analyzed.</p><p><strong>Results: </strong>There was no relationship between the shifts in balance from temporal frequency and monocularly directed attention in both controls and amblyopes. Intermediate temporal frequencies (8.9 ± 1.4 Hz) in one eye maximized its perceptual dominance, with a larger shift due to temporal frequency in amblyopes than in controls. While normally sighted observers experienced similar degrees of shift in balance from temporal frequency and attentional (active and passive) modulations, amblyopic observers experienced a larger shift from temporal frequency than from monocularly focused passive (but not active) attention.</p><p><strong>Conclusions: </strong>Intermediate temporal frequencies in one eye, rather than a specific temporal frequency difference between both eyes, maximized its perceptual dominance in both normally sighted and amblyopic observers. This balance shift from temporal frequency modulation was larger in amblyopes than in controls. Finally, the effect of temporal frequency on balance was larger than that of monocularly directed passive attention in amblyopes.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 4","pages":"8"},"PeriodicalIF":5.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11967993/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143763387","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Min Gao, Yukun Guo, Tristan T Hormel, Jie Wang, Elizabeth White, Dong-Wouk Park, Thomas S Hwang, Steven T Bailey, Yali Jia
{"title":"Nonperfused Retinal Capillaries-A New Method Developed on OCT and OCTA.","authors":"Min Gao, Yukun Guo, Tristan T Hormel, Jie Wang, Elizabeth White, Dong-Wouk Park, Thomas S Hwang, Steven T Bailey, Yali Jia","doi":"10.1167/iovs.66.4.22","DOIUrl":"https://doi.org/10.1167/iovs.66.4.22","url":null,"abstract":"<p><strong>Purpose: </strong>This study aims to develop a new method to quantify nonperfused retinal capillaries (NPCs) and evaluate NPCs in eyes with AMD and diabetic retinopathy (DR).</p><p><strong>Methods: </strong>We averaged multiple registered optical coherence tomography (OCT)/OCT angiography (OCTA) scans to create high-definition volumes. The deep capillary plexus slab was defined and segmented. A developed deep learning denoising algorithm removed tissue background noise from capillaries in en face OCT/OCTA. The algorithm segmented NPCs by identifying capillaries from OCT without corresponding flow signals in OCTA. We then investigated the relationships between NPCs and known features in AMD and DR.</p><p><strong>Results: </strong>The segmented NPC achieved an accuracy of 88.2% compared to manual grading of NPCs in DR. Compared to healthy controls, both the mean number and total length (mm) of NPCs was significantly increased in AMD and DR eyes (P < 0.001, P < 0.001). Compared to early and intermediate AMD, the number and total length of NPCs were significantly higher in advanced AMD (number: P < 0.001, P < 0.001; total length: P = 0.002, P = 0.003). Geography atrophy, macular neovascularization, drusen volume, and extrafoveal avascular area (EAA) significantly correlated with increased NPCs (P < 0.05). In DR eyes, NPCs correlated with the number of microaneurysms and EAA (P < 0.05). The presence of fluid did not significantly correlate with NPCs in AMD and DR.</p><p><strong>Conclusions: </strong>A deep learning-based algorithm can segment and quantify retinal capillaries that lack flow using colocalized OCT/OCTA. This new biomarker may be useful in AMD and DR in predicting progression of these diseases.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 4","pages":"22"},"PeriodicalIF":5.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143811334","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}