Investigative ophthalmology & visual science最新文献

{"title":"Gene Identification for Ocular Congenital Cranial Motor Neuron Disorders Using Human Sequencing, Zebrafish Screening, and Protein Binding Microarrays.","authors":"Julie A Jurgens, Paola M Matos Ruiz, Jessica King, Emma E Foster, Lindsay Berube, Wai-Man Chan, Brenda J Barry, Raehoon Jeong, Elisabeth Rothman, Mary C Whitman, Sarah MacKinnon, Cristina Rivera-Quiles, Brandon M Pratt, Teresa Easterbrooks, Fiona M Mensching, Silvio Alessandro Di Gioia, Lynn Pais, Eleina M England, Teresa de Berardinis, Adriano Magli, Feray Koc, Kazuhide Asakawa, Koichi Kawakami, Anne O'Donnell-Luria, David G Hunter, Caroline D Robson, Martha L Bulyk, Elizabeth C Engle","doi":"10.1167/iovs.66.3.62","DOIUrl":"https://doi.org/10.1167/iovs.66.3.62","url":null,"abstract":"<p><strong>Purpose: </strong>To functionally evaluate novel human sequence-derived candidate genes and variants for unsolved ocular congenital cranial dysinnervation disorders (oCCDDs).</p><p><strong>Methods: </strong>Through exome and genome sequencing of a genetically unsolved human oCCDD cohort, we previously reported the identification of variants in many candidate genes. Here, we describe a parallel study that prioritized a subset of these genes (43 human genes, 57 zebrafish genes) using a G0 CRISPR/Cas9-based knockout assay in zebrafish and generated F2 germline mutants for 17. We tested the functionality of variants of uncertain significance in known and novel candidate transcription factor-encoding genes through protein binding microarrays.</p><p><strong>Results: </strong>We first demonstrated the feasibility of the G0 screen by targeting known oCCDD genes phox2a and mafba. Approximately 70% to 90% of gene-targeted G0 zebrafish embryos recapitulated germline homozygous null-equivalent phenotypes. Using this approach, we then identified three novel candidate oCCDD genes (SEMA3F, OLIG2, and FRMD4B) with putative contributions to human and zebrafish cranial motor development. In addition, protein binding microarrays demonstrated reduced or abolished DNA binding of human variants of uncertain significance in known and novel sequence-derived transcription factors PHOX2A (p.(Trp137Cys)), MAFB (p.(Glu223Lys)), and OLIG2 (p.(Arg156Leu)).</p><p><strong>Conclusions: </strong>This study nominates three strong novel candidate oCCDD genes (SEMA3F, OLIG2, and FRMD4B) and supports the functionality and putative pathogenicity of transcription factor candidate variants PHOX2A p.(Trp137Cys), MAFB p.(Glu223Lys), and OLIG2 p.(Arg156Leu). Our findings support that G0 loss-of-function screening in zebrafish can be coupled with human sequence analysis and protein binding microarrays to aid in prioritizing oCCDD candidate genes/variants.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 3","pages":"62"},"PeriodicalIF":5.0,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143752774","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":"Whorl-Like Collagen Fiber Arrangement Around Emissary Canals in the Posterior Sclera.","authors":"Hongshuang Lu, Yijin Wu, Jianping Xiong, Nan Zhou, Masahiro Yamanari, Michiaki Okamoto, Keigo Sugisawa, Hiroyuki Takahashi, Changyu Chen, Yining Wang, Ziye Wang, Kyoko Ohno-Matsui","doi":"10.1167/iovs.66.3.35","DOIUrl":"10.1167/iovs.66.3.35","url":null,"abstract":"<p><strong>Purpose: </strong>To investigate the collagen fiber arrangement around emissary canals in the posterior sclera.</p><p><strong>Methods: </strong>One hundred sixty-five eyes of 93 patients who underwent polarization-sensitive optical coherence tomography (PS-OCT) examinations in 2019 in the Institute of Science Tokyo were studied. Multimodal imaging, including streamline images derived from PS-OCT data, B-scan images, and indocyanine green angiography (ICGA) images, was used to investigate the collagen fiber arrangement around emissary canals and scleral pits in vivo. Additionally, the collagen fiber arrangement around the emissary canals in porcine sclera was examined using scanning electron microscopy and light microscopy.</p><p><strong>Results: </strong>Streamline images showed whorl-like collagen fiber arrangements on all eyes, and 25 eyes were selected for the analysis. All whorls corresponded to emissary canals on B-scan images. The whorls were confirmed to correspond to the posterior ciliary artery entries in three eyes and posterior vortex vein exits in three eyes with available ICGA images. Streamline cutaway images showed that the whorls surrounded the emissary canals throughout the entire course. In 16 eyes with 20 scleral pits, whorls were seen surrounding all the pits. Microscopic study using porcine sclera confirmed the whorl-like structures around the emissary canals ex vivo and demonstrated tangentially arranged collagen fiber bundles forming the circle.</p><p><strong>Conclusions: </strong>The collagen fibers are arranged as whorl-like structures around the vessel emissary canals in the posterior sclera, which is a knowledge gap for basic scleral histology. Additionally, this study demonstrated a strong correlation between PS-OCT findings and microscopic histology, underscoring PS-OCT's utility in detecting scleral collagen fiber arrangements.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 3","pages":"35"},"PeriodicalIF":5.0,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11927319/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143657073","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":"Corneal Keratocytes, Fibroblasts, and Myofibroblasts Exhibit Distinct Transcriptional Profiles In Vitro.","authors":"Kara Poole, Krithika S Iyer, David W Schmidtke, W Matthew Petroll, Victor D Varner","doi":"10.1167/iovs.66.3.28","DOIUrl":"10.1167/iovs.66.3.28","url":null,"abstract":"<p><strong>Purpose: </strong>After stromal injury to the cornea, the release of growth factors and pro-inflammatory cytokines promotes the activation of quiescent keratocytes into a migratory fibroblast and/or fibrotic myofibroblast phenotype. Persistence of the myofibroblast phenotype can lead to corneal fibrosis and scarring, which are leading causes of blindness worldwide. This study aims to establish comprehensive transcriptional profiles for cultured corneal keratocytes, fibroblasts, and myofibroblasts to gain insights into the mechanisms through which these phenotypic changes occur.</p><p><strong>Methods: </strong>Primary rabbit corneal keratocytes were cultured in either defined serum-free (SF) media, fetal bovine serum (FBS) containing media, or SF media supplemented with TGF-β1 to induce keratocyte, fibroblast, or myofibroblast phenotypes, respectively. Bulk RNA sequencing followed by bioinformatic analyses was performed to identify significant differentially expressed genes (DEGs) and enriched biological pathways for each phenotype.</p><p><strong>Results: </strong>Genes commonly associated with keratocytes, fibroblasts, or myofibroblasts showed high relative expression in SF, FBS, or TGF-β1 culture conditions, respectively. Differential expression and functional analyses revealed novel DEGs for each cell type, as well as enriched pathways indicative of differences in proliferation, apoptosis, extracellular matrix (ECM) synthesis, cell-ECM interactions, cytokine signaling, and cell mechanics.</p><p><strong>Conclusions: </strong>Overall, these data demonstrate distinct transcriptional differences among cultured corneal keratocytes, fibroblasts, and myofibroblasts. We have identified genes and signaling pathways that may play important roles in keratocyte differentiation, including many related to mechanotransduction and ECM biology. Our findings have revealed novel molecular markers for each cell type, as well as possible targets for modulating cell behavior and promoting physiological corneal wound healing.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 3","pages":"28"},"PeriodicalIF":5.0,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11918030/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143604805","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":"Effects of a Hyperbaric Normoxic Environment on the Retina and Choroid.","authors":"Nur Demir, Belma Kayhan, Yavuz Aslan","doi":"10.1167/iovs.66.3.47","DOIUrl":"10.1167/iovs.66.3.47","url":null,"abstract":"<p><strong>Purpose: </strong>Divers and individuals working in submarines and other underwater environments are exposed to normoxic hyperbaric conditions frequently. The aim of this study was to evaluate the effects of hyperbaric normoxia on the retina and choroid.</p><p><strong>Methods: </strong>Healthy participants with no prior diving experience were exposed to 2.4 atmospheres absolute pressure in a normoxic hyperbaric chamber (HC). Optical coherence tomography was used to measure retinal thickness, the peripapillary retinal nerve fiber layer, and choroidal thickness (CT) before and within 30 minutes after HC exposure.</p><p><strong>Results: </strong>The right eyes of 42 participants (mean age, 23.88 ± 2.85 years) were included in the study. The retinal nerve fiber layer thickness significantly decreased in the central 1-mm Early Treatment Diabetic Retinopathy Study (ETDRS) subfield after HC exposure (P < 0.05). The outer plexiform layer showed significant thickening in the central 1-mm ETDRS subfield (P < 0.05). The retinal pigment epithelium (RPE) thickness in the 3-mm ETDRS subfield significantly decreased after HC exposure (P < 0.01). Furthermore, nasal CT (P < 0.05), temporal CT (P < 0.05), and mean CT (P < 0.01) significantly increased after HC exposure.</p><p><strong>Conclusions: </strong>This study is the first in which the effects of a hyperbaric normoxic environment on the retina and choroid were examined. The observed increases in outer plexiform layer and CTs may result from elevated intracranial perfusion pressure, likely owing to increased venous pressure with unchanged cerebral arterial blood flow under hyperbaric normoxic conditions. Elevated intracranial perfusion pressure may also contribute to venous stasis in the retinochoroidal circulation, potentially explaining the structural changes observed in this study.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 3","pages":"47"},"PeriodicalIF":5.0,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11935558/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143673879","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":"Three-Dimensional β-Amyloid Burden Correlation Between the Eye and Brain in Alzheimer's Disease Mice Using Light-Sheet Fluorescence Microscopy.","authors":"Hye Joo Son, Seonok Kim, Seog-Young Kim, Jin Hwa Jung, Suk Hyun Lee, Soo-Jong Kim, Chanwoo Kim, Alice Hahn","doi":"10.1167/iovs.66.3.34","DOIUrl":"10.1167/iovs.66.3.34","url":null,"abstract":"<p><strong>Purpose: </strong>Recent studies have highlighted the significance of peripheral β-amyloid (Aβ) deposition, identifying the eye as a potential early detection site for Alzheimer's disease (AD). However, previous two-dimensional AD ocular studies have been unable to establish a clear correlation between the three-dimensional Aβ accumulation in the entire eyeball and brain while preserving structural integrity. This study employed a combined brain amyloid positron emission tomography/magnetic resonance (PET/MR) and light-sheet fluorescence microscopy (LSFM) platform to assess whether the three-dimensionally measured Aβ burden in the eyeball correlates with that in the brain.</p><p><strong>Methods: </strong>Thirteen eyeballs (6 AD, 7 control) and 17 brains (10 AD, 7 control) were collected from ten 44-week-old 5xFAD and seven control mice. The samples underwent tissue clearing and staining with thioflavin S (Aβ), anti-CD11b (microglia), and anti-ACSA-2 (astrocytes) for LSFM imaging and quantified via 3D surface volume. Standardized uptake value ratios from [18F]Flutemetamol PET/MR were also calculated.</p><p><strong>Results: </strong>AD eyeballs presented significantly greater plaque-like surface volumes (median, 51,091,002 µm³ [interquartile range, 38,488,272-64,869,828]) than controls (229,293 µm³ [115,863-311,5320]; P = 0.001). AD brains exhibited higher [18F]Flutemetamol uptake and greater plaque-like surface volumes (898,634,368 µm³ [556,263,488-1,105,326,720]) than controls (33,320,178 µm³ [26,842,538-62,716,956]; P < 0.001). A strong positive correlation was observed between the plaque-like surface volumes in the brain and that in the eyeball (r = 0.810, P = 0.001). No significant correlations were found in other morphologic parameters.</p><p><strong>Conclusions: </strong>Our observation of a strong correlation between the three-dimensional Aβ burden in the whole eyeball and brain advances our understanding of the systemic nature of Aβ pathology and suggests ocular Aβ as a potential independent predictor of brain Aβ burden.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 3","pages":"34"},"PeriodicalIF":5.0,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11932423/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143657069","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":"The Spatial Transcriptomic Atlas of Human Limbus and Vital Niche Microenvironment Regulating the Fate of Limbal Epithelial Stem Cells.","authors":"Shiding Li, Hao Sun, Fei Fang, Siyi Zhang, Junzhao Chen, Chunyi Shao, Yao Fu, Liangbo Chen","doi":"10.1167/iovs.66.3.52","DOIUrl":"10.1167/iovs.66.3.52","url":null,"abstract":"<p><strong>Purpose: </strong>This study aimed to generate the spatial atlas of the human limbus using spatial transcriptomic technology and reveal the deep interaction among the niche microenvironment.</p><p><strong>Methods: </strong>The spatial transcriptomic atlas of human limbus was performed using 10× Genomics Space Ranger software platform. Single-cell RNA sequencing data of human limbal epithelial stem cells (LESCs) were downloaded for integrating analysis.</p><p><strong>Results: </strong>We profiled more than 400 spots within each sample and spatially located major cell types within the limbus area. LESCs were localized mainly in the basement membrane, and limbal niche cells were situated predominantly within the stromal area. Next, the limbus was divided into four regions based on histological structure, and the differential expressed genes among the four regions were analyzed. Notably, GPHB5 was highly expressed in the epithelium of the middle region and co-staining with deltaNp63 suggested it might be a novel potential biomarker of LESCs. Subsequently, limbal mesenchymal stem cells were found to exhibit the greatest amounts of ligands associated with LESCs. The widespread activity of COL6A2/CD44 signaling among limbal mesenchymal stem cells, melanocytes, immune cells, and LESCs indicate its essential role in mediating bidirectional communication via the collagen pathway.</p><p><strong>Conclusions: </strong>This research mapped the spatial positioning of key cells within the limbal niche and detailed interactions between major cell types. These findings provide a foundation for further LESC research and enhance our understanding of corneal biology.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 3","pages":"52"},"PeriodicalIF":5.0,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11951063/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143700325","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":"Three-Dimensional Choroidal Vessels Assessment in Diabetic Retinopathy.","authors":"Elham Sadeghi, Katherine Du, Oluwaseyi Ajayi, Elli Davis, Nicola Valsecchi, Mohammed Nasar Ibrahim, Sandeep Chandra Bollepalli, Kiran Kumar Vupparaboina, Jose Alain Sahel, Jay Chhablani","doi":"10.1167/iovs.66.3.50","DOIUrl":"10.1167/iovs.66.3.50","url":null,"abstract":"<p><strong>Purpose: </strong>To evaluate choroidal vasculature in eyes with diabetic retinopathy (DR) using a novel three-dimensional algorithm.</p><p><strong>Methods: </strong>Patients with DR and healthy controls underwent clinical examinations and swept-source optical coherence tomography (PlexElite-9000). The choroidal layer was segmented using the ResUNet model. Phansalkar thresholding was used to binarize the choroidal vasculature. The macular area was divided into 5 sectors by a custom grid, and the 15 largest vessels in each sector were measured for mean choroidal vessel diameter (MChVD). Volumetric choroidal thickness (ChT) and the choroidal vascularity index (CVI) were calculated. A linear mixed model was used for analysis.</p><p><strong>Results: </strong>This retrospective cross-sectional study analyzed 73 eyes of 45 patients with DR (36 proliferative vs. 37 nonproliferative DR, and 42 with diabetic macular edema [DME] vs. 31 without DME), and 27 eyes of 21 age-match controls. The average MChVD was decreased in DR compared with healthy (200.472 ± 28.246 µm vs. 240.264 ± 22.350 µm; P < 0.001), as well as lower sectoral MChVD (P < 0.001); however, there was no difference in average ChT between the groups (P > 0.05). The global CVI was reduced in DR, especially in temporal and central sectors (P < 0.05). Compared with nonproliferative, proliferative DR exhibited decreased ChT (temporal, P < 0.05; other sectors, P > 0.05), CVI (P > 0.05), and MChVD (P > 0.05). DME eyes demonstrated lower but not statistically significant MChVD (196.449 ± 27.221 µm vs. 205.922 ± 29.134 µm; P > 0.05) and significantly reduced average CVI (0.365 ± 0.032 vs. 0.389 ± 0.040; P = 0.008) compared with non-DME eyes.</p><p><strong>Conclusions: </strong>DR and DME eyes showed reduced MChVD and CVI, likely owing to microvascular changes leading to ischemia. These findings highlight the need for new choroidal biomarkers to better understand DR's pathogenic mechanisms.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 3","pages":"50"},"PeriodicalIF":5.0,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11951060/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143700335","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":"Orbital Clinicopathological Differences in Thyroid Eye Disease: An Analysis of Cytokines With Histopathological and Clinical Correlation.","authors":"Yue Li, Jiaqi Tang, Gaojing Jing, Yueyue Li, Rui Ma, Xin Kang, Liyuan Rong, Wenlu Liu, Lan Yao, Xiaohui Lv, Aijun Deng, Wei Wu, Xinji Yang","doi":"10.1167/iovs.66.3.33","DOIUrl":"10.1167/iovs.66.3.33","url":null,"abstract":"<p><strong>Purpose: </strong>To explore the pathological differences in orbital adipose/connective tissue between active and inactive thyroid eye disease (TED) subjects and their correlations with clinical characteristics.</p><p><strong>Methods: </strong>Orbital adipose/connective tissue samples from 42 TED subjects (20 active, 22 inactive) were collected during decompression surgery. We analyzed cytokine expression, inflammatory cell infiltration, inherent cell populations, and interstitial changes by Luminex and histopathology. Correlations were analyzed using Pearson and Spearman correlation analyses.</p><p><strong>Results: </strong>Among the 108 cytokines detected, active TED exhibited elevated platelet endothelial cell adhesion molecule 1 (PECAM-1), interleukin-23 (IL-23), a proliferation-inducing ligand (APRIL), IL-6, C-C motif chemokine ligand 2 (CCL2), β-nerve growth factor (NGF), and lower CCL21 and CCL5. The extent of infiltration by helper T (Th) cells and monocytes was significantly greater in the active group than in the inactive group. Adipocyte density was significantly elevated in active TED, whereas fibrosis was more prominent in inactive TED. Fifteen cytokines were significantly associated with inflammatory cell infiltration, with IL-16 showing the strongest correlations with T cells. Ten cytokines showed significant positive correlations with fibrosis. Four cytokines (IL-6, PECAM-1, IL-23 and transforming growth factor β1), Th cell infiltration and adipocyte density were significantly positively correlated with clinical activity score (CAS). Sixteen cytokines, along with adipocyte density, were significantly positively correlated with disease severity of TED.</p><p><strong>Conclusions: </strong>The orbital adipose/connective tissues of active and inactive TED subjects showed significant differences in terms of cytokines, inflammatory cells infiltration, inherent cells and interstitium. These pathological changes were correlated with clinical characteristics of TED.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 3","pages":"33"},"PeriodicalIF":5.0,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11927299/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143656965","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":"An Approach to Predict Intraocular Diseases by Machine Learning Based on Vitreous Humor Immune Mediator Profile.","authors":"Risa Sugawara, Yoshihiko Usui, Akira Saito, Naoya Nezu, Hiroyuki Komatsu, Kinya Tsubota, Masaki Asakage, Naoyuki Yamakawa, Yoshihiro Wakabayashi, Masahiro Sugimoto, Masahiko Kuroda, Hiroshi Goto","doi":"10.1167/iovs.66.3.38","DOIUrl":"10.1167/iovs.66.3.38","url":null,"abstract":"<p><strong>Purpose: </strong>This study aimed to elucidate whether machine learning algorithms applied to vitreous levels of immune mediators predict the diagnosis of 12 representative intraocular diseases, and identify immune mediators driving the predictive power of machine learning model.</p><p><strong>Methods: </strong>Vitreous samples in 522 eyes diagnosed with 12 intraocular diseases were collected, and 28 immune mediators were measured using a cytometric bead array. The significance of each immune mediator was determined by employing five machine learning algorithms. Stratified k-fold cross-validation was performed to divide the dataset into training and test sets. The algorithms were assessed by analyzing precision, recall, accuracy, F-score, area under the receiver operating characteristics curve, area under the precision-recall curve, and feature importance.</p><p><strong>Results: </strong>Of the five machine learning models, random forest attained the maximum accuracy in the classification of 12 intraocular diseases in a multi-class setting. The random forest prediction models for vitreoretinal lymphoma, endophthalmitis, uveal melanoma, rhegmatogenous retinal detachment, and acute retinal necrosis demonstrated superior classification accuracy, precision, and recall. The top three important immune mediators for predicting vitreoretinal lymphoma were IL-10, granzyme A, and IL-6; those for endophthalmitis were IL-6, G-CSF, and IL-8; and those for uveal melanoma were RANTES, IL-8 and bFGF.</p><p><strong>Conclusions: </strong>The random forest algorithm effectively classified 28 immune mediators in the vitreous to accurately predict the diagnosis of vitreoretinal lymphoma, endophthalmitis, and uveal melanoma among 12 representative intraocular diseases. In summary, the results of this study enhance our understanding of potential new biomarkers that may contribute to elucidating the pathophysiology of intraocular diseases in the future.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 3","pages":"38"},"PeriodicalIF":5.0,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11932427/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143656926","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":"Comparison Between MAIA and MP-3 In Healthy Subjects and Patients With Diabetes, Diabetic Retinopathy, and Age-Related Macular Degeneration.","authors":"Anna Marmalidou, Haleema Siddiqui, Muhammad Usman Jamil, Kwang Min Woo, Antonio Yaghy, A Yasin Alibhai, Hiroyuki Takahashi, Stephanie Kaiser, Keith Effert, Peter Y Zhao, Shilpa J Desai, Christopher C Robinson, Jay S Duker, Nadia K Waheed","doi":"10.1167/iovs.66.3.59","DOIUrl":"10.1167/iovs.66.3.59","url":null,"abstract":"<p><strong>Purpose: </strong>The purpose of this study was to assess the comparability of mean sensitivity (MS) values obtained using the Macular Integrity Assessment (MAIA; CenterVue S.p.A. [iCare], Padova, Italy) and Microperimeter-3 (MP-3; NIDEK CO., Ltd., Gamagori, Japan) microperimetry (MP) devices.</p><p><strong>Methods: </strong>This cross-sectional study includes subjects with healthy eyes, eyes with diabetes mellitus without diabetic retinopathy (DM no DR), diabetic retinopathy (DR), and non-exudative age-related macular degeneration (AMD). Patients underwent testing on both MAIA and MP-3 MP devices, using a 10-2 macular grid with 68 stimuli and identical parameters. A diagnosis-adjusted linear regression model and mixed modeling mapped MP-3 MS to MAIA MS and Bland-Altman analysis were used to assess the agreement.</p><p><strong>Results: </strong>One hundred eleven eyes (43 healthy eyes, 14 eyes with DM no DR, 32 eyes with DR, and 22 eyes with AMD) from 80 subjects (age = 57.2 ± 20.3 years) were enrolled. MAIA consistently showed higher MS than MP-3. The MP-3 device detected absolute scotomatous points in more eyes than MAIA (6 eyes [MAIA] vs. 10 eyes [MP-3]). Healthy eyes exhibited stronger agreements than those with DR (P < 0.001) or AMD (P = 0.015). Converting MP-3 to MAIA MS improved agreement and reduced coefficients of repeatability (CoRs) but did not fully account for inter-device variability. MP-3 classified more eyes as having relatively unstable or unstable fixation than MAIA (P = 0.014).</p><p><strong>Conclusions: </strong>Both devices effectively detect retinal functional changes and scotomas. The conversion methods developed in this study can aid cross-device comparisons, but retinal pathologies (DM and AMD) introduce additional inter-device variability. Future studies incorporating multiple devices should account for this variability in their study design.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 3","pages":"59"},"PeriodicalIF":5.0,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11954536/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143730093","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}