Ophthalmology science最新文献

{"title":"Biological and Methodological Variability in Retinal Nerve Fiber Layer OCT: The Framingham Heart Study","authors":"","doi":"10.1016/j.xops.2024.100549","DOIUrl":"10.1016/j.xops.2024.100549","url":null,"abstract":"<div><h3>Objective</h3><p>To explore participant-level biological attributes and scan-level methodological attributes associated with retinal nerve fiber layer (RNFL) thickness variability in a population-based sample of elderly United States adults.</p></div><div><h3>Design</h3><p>Cross-sectional analysis using data from the Framingham Heart Study.</p></div><div><h3>Participants</h3><p>One thousand three hundred forty-seven eyes from 825 participants with ≥1 OCT scan and axial length data were included.</p></div><div><h3>Methods</h3><p>Three or more successive RNFL scans of each eye of each participant were obtained in a single session. Multivariable linear mixed models were employed to explore the associations between average RNFL thickness with participant-level biological attributes (age, gender, race, ethnicity, and axial length) and scan-level attributes (signal strength [SS]) as independent variables in the whole population as well as a subsample of adults with no self-reported history of glaucoma. Similar analyses were designed to assess methodological variability with average within-eye standard deviation (SD) for repeated scans as the dependent variable.</p></div><div><h3>Main Outcomes Measures</h3><p>(1) Biological variability: average RNFL thickness, and (2) methodological variability: average within-participant SD across repeated scans.</p></div><div><h3>Results</h3><p>Age (β = <span><math><mrow><mo>−</mo></mrow></math></span>0.19 microns/year, [95% confidence interval {CI}: <span><math><mrow><mo>−</mo></mrow></math></span>0.29, <span><math><mrow><mo>−</mo></mrow></math></span>0.09]), female gender (β = +1.48 microns vs. male, [95% CI: 0.09, 2.86]), axial length (β = <span><math><mrow><mo>−</mo></mrow></math></span>1.24 microns/mm of greater length, [95% CI: <span><math><mrow><mo>−</mo></mrow></math></span>1.80, <span><math><mrow><mo>−</mo></mrow></math></span>0.67]), and SS (β = +1.62 microns/1 unit greater SS, [95% CI: 1.16, 2.09]) were significantly associated with RNFL thickness, while race and ethnicity were not (<em>P</em> &gt; 0.05). In analyses designed to assess methodological variability, higher RNFL thickness (β = +0.02 per micron increase, [95% CI: 0.01, 0.03]), and lower SS (β = +0.19 per 1 unit lower SS, [95% CI: 0.10, 0.27]) were significantly associated with greater RNFL variability. In adults with no self-reported history of glaucoma (n of eyes = 1165, n of participants = 712), female gender was not associated with RNFL, while African American race was associated with thicker RNFL (β = +4.65 microns vs. Whites, [95% CI: 1.28, 8.03]).</p></div><div><h3>Conclusions</h3><p>Retinal nerve fiber layer thickness is lower with older age, male gender, greater axial length, lower SS, and Whites (as compared with African Americans) without self-reported glaucoma. Measurement variability (SD) is higher with greater RNFL thickness and lower SS. Understanding these biological and methodological variations is important to aid in OC","PeriodicalId":74363,"journal":{"name":"Ophthalmology science","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S266691452400085X/pdfft?md5=cc59963c5ad70558c0a6d8a005f0137d&pid=1-s2.0-S266691452400085X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141038291","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Next-Generation Tear Meniscus Height Detecting and Measuring Smartphone-Based Deep Learning Algorithm Leads in Dry Eye Management","authors":"Farhad Nejat PhD ,&nbsp;Shima Eghtedari MSc ,&nbsp;Fatemeh Alimoradi MSc","doi":"10.1016/j.xops.2024.100546","DOIUrl":"10.1016/j.xops.2024.100546","url":null,"abstract":"<div><h3>Purpose</h3><p>This study aims to develop and assess an infrastructure using Python-based deep learning code for future diagnostic and management purposes related to dry eye disease (DED) utilizing smartphone images.</p></div><div><h3>Design</h3><p>Cross-sectional study using data which was gathered in Vision Health Research Clinic.</p></div><div><h3>Participants</h3><p>One thousand twenty-one eye images from 734 patients were included in this article that categorizes into 70% females and 30% males, with no sex and age limit.</p></div><div><h3>Methods</h3><p>One specialist captured eye images using Samsung A71 (601 images) and iPhone 11 (420 images) cell phones with the flashlight on and direct gaze to the camera. These images include the area of only 1 eye (left/right).</p></div><div><h3>Main Outcome Measures</h3><p>First, our specialist did 3 different segmentations for every eye image separately for 80% of the training data. This part contains eye, lower eyelid, and iris segmentation. In 20% of test data after automated cropping of the lower eyelid margin and upscaling by 8×, the appropriate tear meniscus height segmentation will be chosen and measured using a deep learning algorithm.</p></div><div><h3>Results</h3><p>The model was trained on 80% of the data and 20% of the data used for validation from both phones with different resolutions. The dice coefficient of the trained model for validation data is 98.68%, and the accuracy of the overall model is 95.39%.</p></div><div><h3>Conclusions</h3><p>It appears that this algorithm holds the potential to herald an evolution in the future of diagnosis and management of DED by homecare devices solely through smartphones.</p></div><div><h3>Financial Disclosure(s)</h3><p>The author(s) have no proprietary or commercial interest in any materials discussed in this article.</p></div>","PeriodicalId":74363,"journal":{"name":"Ophthalmology science","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666914524000824/pdfft?md5=e8a9d417883a01fd9df8932a84f67ac7&pid=1-s2.0-S2666914524000824-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141031162","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An in vitro 3-dimensional Collagen-based Corneal Construct with Innervation Using Human Corneal Cell Lines","authors":"","doi":"10.1016/j.xops.2024.100544","DOIUrl":"10.1016/j.xops.2024.100544","url":null,"abstract":"<div><h3>Purpose</h3><p>To develop a 3-dimensional corneal construct suitable for in vitro studies of disease conditions and therapies.</p></div><div><h3>Design</h3><p>In vitro human corneal constructs were created using chemically crosslinked collagen and chondroitin sulfate extracellular matrix and seeded with 3 human corneal cell types (epithelial, stromal, and endothelial) together with neural cells. The neural cells were derived from hybrid neuroblastoma cells and the other cells used from immortalized human corneal cell lines. To check the feasibility and characterize the constructs, cytotoxicity, cell proliferation, histology, and protein expression studies were performed.</p></div><div><h3>Results</h3><p>Optimized culture condition permitted synchronized viability across the cell types within the construct. The construct showed a typical appearance for different cellular layers, including healthy appearing, phenotypically differentiated neurons. The expected protein expression profiles for specific cell types within the construct were confirmed with western blotting.</p></div><div><h3>Conclusions</h3><p>An in vitro corneal construct was successfully developed with maintenance of individual cell phenotypes with anatomically correct cellular loci. The construct may be useful in evaluation of specific corneal disorders and in developing different corneal disease models. Additionally, the construct can be used in evaluating drug targeting and/or penetration to individual corneal layers, testing novel therapeutics for corneal diseases, and potentially reducing the necessity for animals in corneal research at the early stages of investigation.</p></div><div><h3>Financial Disclosure(s)</h3><p>Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.</p></div>","PeriodicalId":74363,"journal":{"name":"Ophthalmology science","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666914524000800/pdfft?md5=c22eb7c9a76bdd6a88cefc0c04de2db4&pid=1-s2.0-S2666914524000800-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141050291","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Factors Associated with Missing Sociodemographic Data in the IRIS® (Intelligent Research in Sight) Registry","authors":"Connor Ross BS ,&nbsp;Alexander Ivanov MS ,&nbsp;Tobias Elze PhD ,&nbsp;Joan W. Miller MD ,&nbsp;Flora Lum MD ,&nbsp;Alice C. Lorch MD, MPH ,&nbsp;Isdin Oke MD, MPH ,&nbsp;IRIS® Registry Analytic Center Consortium","doi":"10.1016/j.xops.2024.100542","DOIUrl":"10.1016/j.xops.2024.100542","url":null,"abstract":"<div><h3>Purpose</h3><p>To describe the prevalence of missing sociodemographic data in the IRIS® (Intelligent Research in Sight) Registry and to identify practice-level characteristics associated with missing sociodemographic data.</p></div><div><h3>Design</h3><p>Cross-sectional study.</p></div><div><h3>Participants</h3><p>All patients with clinical encounters at practices participating in the IRIS Registry prior to December 31, 2020.</p></div><div><h3>Methods</h3><p>We describe geographic and temporal trends in the prevalence of missing data for each sociodemographic variable (age, sex, race, ethnicity, geographic location, insurance type, and smoking status). Each practice contributing data to the registry was categorized based on the number of patients, number of physicians, geographic location, patient visit frequency, and patient population demographics.</p></div><div><h3>Main Outcome Measures</h3><p>Multivariable linear regression was used to describe the association of practice-level characteristics with missing patient-level sociodemographic data.</p></div><div><h3>Results</h3><p>This study included the electronic health records of 66 477 365 patients receiving care at 3306 practices participating in the IRIS Registry. The median number of patients per practice was 11 415 (interquartile range: 5849–24 148) and the median number of physicians per practice was 3 (interquartile range: 1–7). The prevalence of missing patient sociodemographic data were 0.1% for birth year, 0.4% for sex, 24.8% for race, 30.2% for ethnicity, 2.3% for 3-digit zip code, 14.8% for state, 5.5% for smoking status, and 17.0% for insurance type. The prevalence of missing data increased over time and varied at the state-level. Missing race data were associated with practices that had fewer visits per patient (<em>P</em> &lt; 0.001), cared for a larger nonprivately insured patient population (<em>P</em> = 0.001), and were located in urban areas (<em>P</em> &lt; 0.001). Frequent patient visits were associated with a lower prevalence of missing race (<em>P</em> &lt; 0.001), ethnicity (<em>P</em> &lt; 0.001), and insurance (<em>P</em> &lt; 0.001), but a higher prevalence of missing smoking status (<em>P</em> &lt; 0.001).</p></div><div><h3>Conclusions</h3><p>There are geographic and temporal trends in missing race, ethnicity, and insurance type data in the IRIS Registry. Several practice-level characteristics, including practice size, geographic location, and patient population, are associated with missing sociodemographic data. While the prevalence and patterns of missing data may change in future versions of the IRIS registry, there will remain a need to develop standardized approaches for minimizing potential sources of bias and ensure reproducibility across research studies.</p></div><div><h3>Financial Disclosure(s)</h3><p>Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.</p></div>","PeriodicalId":74363,"journal":{"name":"Ophthalmology science","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666914524000782/pdfft?md5=9f01027aeda71e03dab8f257df85f964&pid=1-s2.0-S2666914524000782-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141949711","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Is CONNECTDROP®, a Medication Event Monitoring System Add-On Paired with a Smartphone Application, Acceptable to Patients with Glaucoma for Taking Their Daily Medication? The CONDORE Pilot Study","authors":"Jean-Baptiste Dériot MD,&nbsp;Emmanuelle Albertini MD","doi":"10.1016/j.xops.2024.100541","DOIUrl":"10.1016/j.xops.2024.100541","url":null,"abstract":"<div><h3>Objective</h3><p>This pilot study tested the feasibility of a future efficacy trial examining the effect of CONNECTDROP®, a novel Medication Event Monitoring System (MEMS) paired with a mHealth application, on medication adherence in patients with glaucoma.</p></div><div><h3>Design</h3><p>A single-center, single-arm, prospective interventional pilot study (NCT04552964).</p></div><div><h3>Participants</h3><p>Adults with glaucoma managed with at least a fixed combination of timolol/dorzolamide who are adherent to treatment.</p></div><div><h3>Methods</h3><p>Participants (n = 31) were provided with the MEMS device and a smartphone with the application installed. They were required to use the MEMS with their usual timolol/dorzolamide prescription for 9 weeks. The study endpoint was at the end of week 9, when all study materials were returned, and participants completed a 17-item patient satisfaction questionnaire. Data collected continuously by each MEMS for the 9 weeks were analyzed for their suitability to quantify adherence of the individual participant and characterize adherence trends within the study cohort. Clinical data were collected at baseline, week 8, and week 9 for the safety evaluation.</p></div><div><h3>Main Outcome Measures</h3><p>The primary outcome was global patient satisfaction after 9 weeks. Secondary outcome measures included participant feedback on handling the MEMS and its usability, along with that of the connected application. Objective data were used to determine participant medication adherence. The proportion of participants who successfully changed the MEMS to a new bottle at week 8 was reported.</p></div><div><h3>Results</h3><p>The MEMS-connected device achieved a global satisfaction score of 74.1% from study participants after 9 weeks. Furthermore, 70.4% of participants found the MEMS easy to use. However, only 59.2% reported feedback from the mHealth application useful in reminding them to take their treatment. MEMS-derived data showed that 70.4% of participants achieved an \"adherence score\" of 80% or above after 8 weeks and that 40.7% who completed the study had not changed the bottle correctly. No adverse events (AEs) were reported.</p></div><div><h3>Conclusion</h3><p>In this pilot study, the CONNECTDROP device was able to monitor daily intake of anti-glaucomatous medication over 2 months and had high satisfaction amongst this cohort of patients and was easy to use. The objective adherence data obtained appears reliable but must be validated for use in an efficacy trial.</p></div><div><h3>Financial Disclosure(s)</h3><p>The authors have no proprietary or commercial interest in any materials discussed in this article.</p></div>","PeriodicalId":74363,"journal":{"name":"Ophthalmology science","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666914524000770/pdfft?md5=1bdc170bfbfc89972b19e2ec9e55ee84&pid=1-s2.0-S2666914524000770-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142162507","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Highly Accurate and Precise Automated Cup-to-Disc Ratio Quantification for Glaucoma Screening","authors":"Abadh K. Chaurasia MOptom ,&nbsp;Connor J. Greatbatch MBBS ,&nbsp;Xikun Han PhD ,&nbsp;Puya Gharahkhani PhD ,&nbsp;David A. Mackey MD, FRANZCO ,&nbsp;Stuart MacGregor PhD ,&nbsp;Jamie E. Craig MBBS, PhD ,&nbsp;Alex W. Hewitt MBBS, FRANZCO, PhD","doi":"10.1016/j.xops.2024.100540","DOIUrl":"https://doi.org/10.1016/j.xops.2024.100540","url":null,"abstract":"<div><h3>Objective</h3><p>An enlarged cup-to-disc ratio (CDR) is a hallmark of glaucomatous optic neuropathy. Manual assessment of the CDR may be less accurate and more time-consuming than automated methods. Here, we sought to develop and validate a deep learning–based algorithm to automatically determine the CDR from fundus images.</p></div><div><h3>Design</h3><p>Algorithm development for estimating CDR using fundus data from a population-based observational study.</p></div><div><h3>Participants</h3><p>A total of 181 768 fundus images from the United Kingdom Biobank (UKBB), Drishti_GS, and EyePACS.</p></div><div><h3>Methods</h3><p>FastAI and PyTorch libraries were used to train a convolutional neural network–based model on fundus images from the UKBB. Models were constructed to determine image gradability (classification analysis) as well as to estimate CDR (regression analysis). The best-performing model was then validated for use in glaucoma screening using a multiethnic dataset from EyePACS and Drishti_GS.</p></div><div><h3>Main Outcome Measures</h3><p>The area under the receiver operating characteristic curve and coefficient of determination.</p></div><div><h3>Results</h3><p>Our gradability model vgg19_batch normalization (bn) achieved an accuracy of 97.13% on a validation set of 16 045 images, with 99.26% precision and area under the receiver operating characteristic curve of 96.56%. Using regression analysis, our best-performing model (trained on the vgg19_bn architecture) attained a coefficient of determination of 0.8514 (95% confidence interval [CI]: 0.8459–0.8568), while the mean squared error was 0.0050 (95% CI: 0.0048–0.0051) and mean absolute error was 0.0551 (95% CI: 0.0543–0.0559) on a validation set of 12 183 images for determining CDR. The regression point was converted into classification metrics using a tolerance of 0.2 for 20 classes; the classification metrics achieved an accuracy of 99.20%. The EyePACS dataset (98 172 healthy, 3270 glaucoma) was then used to externally validate the model for glaucoma classification, with an accuracy, sensitivity, and specificity of 82.49%, 72.02%, and 82.83%, respectively.</p></div><div><h3>Conclusions</h3><p>Our models were precise in determining image gradability and estimating CDR. Although our artificial intelligence–derived CDR estimates achieve high accuracy, the CDR threshold for glaucoma screening will vary depending on other clinical parameters.</p></div><div><h3>Financial Disclosure(s)</h3><p>Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.</p></div>","PeriodicalId":74363,"journal":{"name":"Ophthalmology science","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666914524000769/pdfft?md5=2051286bae03382c02eff7d1df69d56a&pid=1-s2.0-S2666914524000769-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141542694","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Liquid Biopsy for Proliferative Diabetic Retinopathy: Single-Cell Transcriptomics of Human Vitreous Reveals Inflammatory T-Cell Signature","authors":"Rachana Haliyur MD, PhD ,&nbsp;David H. Parkinson MS ,&nbsp;Feiyang Ma PhD ,&nbsp;Jing Xu PhD ,&nbsp;Qiang Li MD, PhD ,&nbsp;Yuanhao Huang ,&nbsp;Lam C. Tsoi PhD ,&nbsp;Rachael Bogle MS ,&nbsp;Jie Liu PhD ,&nbsp;Johann E. Gudjonsson MD ,&nbsp;Rajesh C. Rao MD","doi":"10.1016/j.xops.2024.100539","DOIUrl":"10.1016/j.xops.2024.100539","url":null,"abstract":"<div><h3>Purpose</h3><p>Current therapies for proliferative diabetic retinopathy (PDR) do not specifically target VEGF-independent, cell-type–specific processes that lead to vision loss, such as inflammatory pathways. This study aimed to identify targetable cell types and corresponding signaling pathways by elucidating the single-cell landscape of the vitreous of patients with PDR.</p></div><div><h3>Design</h3><p>Case series.</p></div><div><h3>Subjects</h3><p>Vitreous and peripheral blood obtained from 5 adult patients (6 eyes) undergoing pars plana vitrectomy for vision-threatening PDR.</p></div><div><h3>Methods</h3><p>Single-cell RNA sequencing (scRNA-seq) was performed on vitreous cells obtained from diluted cassette washings during vitrectomy from 6 eyes and peripheral blood mononuclear cells (PBMCs, n = 5). Droplet-based scRNA-seq was performed using the Chromium 10x platform to obtain single-cell transcriptomes. Differences in tissue compartments were analyzed with gene ontology enrichment of differentially expressed genes and an unbiased ligand–receptor interaction analysis.</p></div><div><h3>Main Outcome Measures</h3><p>Single-cell transcriptomic profiles of vitreous and peripheral blood.</p></div><div><h3>Results</h3><p>Transcriptomes from 13 675 surgically harvested vitreous cells and 22 636 PBMCs were included. Clustering revealed 4 cell states consistently across all eyes with representative transcripts for T cells (<em>CD2</em>, <em>CD3D</em>, <em>CD3E</em>, and <em>GZMA</em>), B cells (<em>CD79A</em>, <em>IGHM</em>, <em>MS4A1</em> (CD20), and <em>HLA-DRA</em>), myeloid cells (<em>LYZ</em>, <em>CST3</em>, <em>AIF1</em>, and <em>IFI30</em>), and neutrophils (<em>BASP1</em>, <em>CXCR2</em>, <em>S100A8</em>, and <em>S100A9</em>). Most vitreous cells were T cells (91.6%), unlike the peripheral blood (46.2%), whereas neutrophils in the vitreous were essentially absent. The full repertoire of adaptive T cells including CD4+, CD8+ and T regulatory cells (Treg) and innate immune system effectors (i.e., natural killer T cells) was present in the vitreous. Pathway analysis also demonstrated activation of CD4+ and CD8+ memory T cells and ligand–receptor interactions unique to the vitreous.</p></div><div><h3>Conclusions</h3><p>In the first single-cell transcriptomic characterization of human vitreous in a disease state, we show PDR vitreous is primarily composed of T cells, a critical component of adaptive immunity, with activity and proportions distinct from T cells within the peripheral blood, and neutrophils are essentially absent. These results demonstrate the feasibility of liquid vitreous biopsies via collection of otherwise discarded, diluted cassette washings during vitrectomy to gain mechanistic and therapeutic insights into human vitreoretinal disease.</p></div><div><h3>Financial Disclosure(s)</h3><p>Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.</p></div>","PeriodicalId":74363,"journal":{"name":"Ophthalmology science","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666914524000757/pdfft?md5=b0564bad17268d31be2faeea5ce8b098&pid=1-s2.0-S2666914524000757-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141963046","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Contributions of Lipid-Related Metabolites and Complement Proteins to Early and Intermediate Age-Related Macular Degeneration","authors":"Simon Nusinovici PhD ,&nbsp;Lei Zhou PhD ,&nbsp;Xinyue Wang MS ,&nbsp;Yih Chung Tham PhD ,&nbsp;Xiaomeng Wang PhD ,&nbsp;Tien Yin Wong MD, PhD ,&nbsp;Usha Chakravarthy MD, PhD ,&nbsp;Ching-Yu Cheng MD, PhD","doi":"10.1016/j.xops.2024.100538","DOIUrl":"https://doi.org/10.1016/j.xops.2024.100538","url":null,"abstract":"<div><h3>Objective</h3><p>Our objective was to determine the effects of lipids and complement proteins on early and intermediate age-related macular degeneration (AMD) stages using machine learning models by integrating metabolomics and proteomic data.</p></div><div><h3>Design</h3><p>Nested case–control study.</p></div><div><h3>Subjects and Controls</h3><p>The analyses were performed in a subset of the Singapore Indian Chinese Cohort (SICC) Eye Study. Among the 6753 participants, we randomly selected 155 Indian and 155 Chinese cases of AMD and matched them with 310 controls on age, sex, and ethnicity.</p></div><div><h3>Methods</h3><p>We measured 35 complement proteins and 56 lipids using mass spectrometry and nuclear magnetic resonance, respectively. We first selected the most contributing lipids and complement proteins to early and intermediate AMD using random forest models. Then, we estimated their effects using a multinomial model adjusted for potential confounders.</p></div><div><h3>Main Outcome Measures</h3><p>Age-related macular degeneration was classified using the Beckman classification system.</p></div><div><h3>Results</h3><p>Among the 310 individuals with AMD, 166 (53.5%) had early AMD, and 144 (46.5%) had intermediate AMD. First, high-density lipoprotein (HDL) particle diameter was positively associated with both early and intermediate AMD (odds ratio [OR]_early = 1.69; 95% confidence interval [CI],1.11–2.55 and OR_intermediate = 1.72; 95% CI, 1.11–2.66 per 1-standard deviation increase in HDL diameter). Second, complement protein 2 (C2), complement C1 inhibitor (IC1), complement protein 6 (C6), complement protein 1QC (C1QC) and complement factor H-related protein 1 (FHR1), were associated with AMD. C2 was positively associated with both early and intermediate AMD (OR_early = 1.58; 95% CI, 1.08–2.30 and OR_intermediate = 1.56; 95% CI, 1.04–2.34). C6 was positively (OR_early = 1.41; 95% CI, 1.03–1.93) associated with early AMD. However, IC1 was negatively associated with early AMD (OR_early = 0.62; 95% CI, 0.38–0.99), whereas C1QC (OR_intermediate = 0.63; 95% CI, 0.42–0.93) and FHR1 (OR_intermediate = 0.73; 95% CI, 0.54–0.98) were both negatively associated with intermediate AMD.</p></div><div><h3>Conclusions</h3><p>Although both HDL diameter and C2 levels show associations with both early and intermediate AMD, dysregulations of IC1, C6, C1QC, and FHR1 are only observed at specific stages of AMD. These findings underscore the complexity of complement system dysregulation in AMD, which appears to vary depending on the disease severity.</p></div><div><h3>Financial Disclosure(s)</h3><p>The authors have no proprietary or commercial interest in any materials discussed in this article.</p></div>","PeriodicalId":74363,"journal":{"name":"Ophthalmology science","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666914524000745/pdfft?md5=e3bd3d3b0fc07ddd1b2067bcad6b08f0&pid=1-s2.0-S2666914524000745-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141542757","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ocular Effects of Prenatal Carotenoid Supplementation in the Mother and Her Child: The Lutein and Zeaxanthin in Pregnancy (L-ZIP) Randomized Trial - Report Number 2","authors":"Emmanuel K. Addo OD ,&nbsp;Joanna E. Gorka BS ,&nbsp;Susan J. Allman CCRC ,&nbsp;Deborah Y. Harrison MSc ,&nbsp;Mohsen Sharifzadeh PhD ,&nbsp;Robert O. Hoffman MD ,&nbsp;M. Elizabeth Hartnett MD ,&nbsp;Michael W. Varner MD ,&nbsp;Paul S. Bernstein MD, PhD","doi":"10.1016/j.xops.2024.100537","DOIUrl":"10.1016/j.xops.2024.100537","url":null,"abstract":"<div><h3>Purpose</h3><p>Lutein (L) and zeaxanthin (Z) are xanthophyll carotenoids that have been promoted to enhance maternal health and infant visual and neurodevelopment. In this study, we determined the effects of prenatal L and Z supplementation on systemic and ocular carotenoid status in the mother and her newborn infant (NCT03750968). This report focuses on the ocular effects of prenatal carotenoid supplementation.</p></div><div><h3>Design</h3><p>A prospective randomized clinical trial with 47 subjects randomly assigned by 1:1 allocation to receive standard-of-care prenatal vitamins along with 10 mg L and 2 mg Z softgel (Carotenoid Group) or standard-of-care prenatal vitamins with a placebo softgel (Control Group) starting in the first trimester.</p></div><div><h3>Subjects</h3><p>We enrolled low-risk pregnancy subjects aged ≥18 years from the obstetrics and gynecology clinic of the University of Utah Hospital.</p></div><div><h3>Methods</h3><p>Maternal macular, skin, and serum carotenoid concentrations were measured using autofluorescence imaging, resonance Raman spectroscopy, and high-performance liquid chromatography, respectively. Infants’ ocular carotenoids and retinal architecture were measured by blue light reflectance imaging and spectral-domain OCT, respectively.</p></div><div><h3>Main Outcome Measures</h3><p>Changes in maternal and infant macular pigment, skin, and serum carotenoid status over the study period. Differences in infants’ retinal maturity indicators between the 2 study groups.</p></div><div><h3>Results</h3><p>Following supplementation, there was a statistically significant increase in maternal macular pigment optical volume (<em>P</em> &lt; 0.001) in the Carotenoid Group relative to the Control Group at all study time points, and there was no detectable maternal ocular carotenoid depletion. Infant skin and serum carotenoids increased significantly in the Carotenoid Group compared with the Control Group. As exploratory endpoints, infants in the Carotenoid Group had a 20% increase in macular pigment optical density (<em>P</em> = 0.242) and more mature foveal parameters compared with those in the Control Group.</p></div><div><h3>Conclusion</h3><p>Prenatal carotenoid supplementation significantly increased maternal and infant systemic carotenoids and caused a pattern of increased infant ocular carotenoid status, which may benefit both mothers and their infants’ ocular development and function. This study provides important data to design and power a future multicenter study of prenatal carotenoid supplementation in higher-risk pregnancies.</p></div><div><h3>Financial Disclosure(s)</h3><p>The author(s) have no proprietary or commercial interest in any materials discussed in this article.</p></div>","PeriodicalId":74363,"journal":{"name":"Ophthalmology science","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666914524000733/pdfft?md5=00e617c27d3ef6e20fa85d7a1b992d27&pid=1-s2.0-S2666914524000733-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140761423","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Decreased Circulating Very Small Low-Density Lipoprotein is Likely Causal for Age-Related Macular Degeneration","authors":"Samaneh Farashi PhD ,&nbsp;Roberto Bonelli PhD ,&nbsp;Victoria E. Jackson PhD ,&nbsp;Brendan R.E. Ansell PhD ,&nbsp;Robyn H. Guymer MBBS, PhD ,&nbsp;Melanie Bahlo PhD","doi":"10.1016/j.xops.2024.100535","DOIUrl":"10.1016/j.xops.2024.100535","url":null,"abstract":"<div><h3>Objective</h3><p>Abnormal changes in metabolite levels in serum or plasma have been highlighted in several studies in age-related macular degeneration (AMD), the leading cause of irreversible vision loss. Specific changes in lipid profiles are associated with an increased risk of AMD. Metabolites could thus be used to investigate AMD disease mechanisms or incorporated into AMD risk prediction models. However, whether particular metabolites causally affect the disease has yet to be established.</p></div><div><h3>Design</h3><p>A 3-tiered analysis of blood metabolites in the United Kingdom (UK) Biobank cohort to identify metabolites that differ in AMD patients with evidence for a putatively causal role in AMD.</p></div><div><h3>Participants</h3><p>A total of 72 376 donors from the UK Biobank cohort including participants with AMD (N = 1353) and non-AMD controls (N = 71 023).</p></div><div><h3>Methods</h3><p>We analyzed 325 directly measured or derived blood metabolites from the UK Biobank for 72 376 donors to identify AMD-associated metabolites. Genome-wide association studies for 325 metabolites in 98 316 European participants from the UK Biobank were performed. The causal effects of these metabolites in AMD were tested using a 2-sample Mendelian randomization approach. The predictive value of these measurements together with sex and age was assessed by developing a machine learning classifier.</p></div><div><h3>Main Outcome Measures</h3><p>Evaluating metabolic biomarkers associated with AMD susceptibility and investigating their potential causal contribution to the development of the disease.</p></div><div><h3>Results</h3><p>This study noted age to be the prominent risk factor associated with AMD development. While accounting for age and sex, we identified 84 metabolic markers as significantly (false discovery rate-adjusted <em>P</em> value &lt; 0.05) associated with AMD. Lipoprotein subclasses comprised the majority of the AMD-associated metabolites (39%) followed by several lipoprotein to lipid ratios. Nineteen metabolites showed a likely causative role in AMD etiology. Of these, 6 lipoproteins contain very small, very low-density lipoprotein (VLDL), and phospholipids to total lipid ratio in medium VLDL. Based on this we postulate that depletion of circulating very small VLDLs is likely causal for AMD. The risk prediction model constructed from the metabolites, age and sex, identified age as the primary predictive factor with a much smaller contribution by metabolites to AMD risk prediction.</p></div><div><h3>Conclusions</h3><p>This study underscores the pronounced role of lipids in AMD susceptibility and the likely causal contribution of particular subclasses of lipoproteins to AMD. Our study provides valuable insights into the metabopathological mechanisms of AMD disease development and progression.</p></div>","PeriodicalId":74363,"journal":{"name":"Ophthalmology science","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S266691452400071X/pdfft?md5=dd59b7a474641d6246898e35d7a7604b&pid=1-s2.0-S266691452400071X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140779863","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}