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Prevalence and Associated Factors of Cataract, Cataract Surgery and Postoperative Outcome in an Old Population in Russia: The Ural Very Old Study 俄罗斯老年人群中白内障、白内障手术及术后效果的患病率和相关因素:乌拉尔高龄老人研究
IF 3.2 Q1 OPHTHALMOLOGY Pub Date : 2024-05-07 DOI: 10.1016/j.xops.2024.100545

Purpose

To assess prevalence of cataract and cataract surgery in a very old population in Russia.

Design

Population-based study.

Participants

The Ural Very Old Study included 1526 (81.1%) participants of 1882 eligible individuals aged >85 years.

Methods

Series of ophthalmological examinations.

Main Outcome Measures

Prevalence of cataract and cataract surgery.

Results

The study included 1163 (76.3%) individuals with lens information. Cataract surgery had been performed in 469 right eyes (41.0%; 95% confidence interval [CI]: 38.1–43.9) (92.1% with posterior chamber intraocular lens [IOL]; 4.7% with multifocal IOL) and 479 left eyes (41.6%; 95% CI: 38.7–44.4) (92.7% with posterior chamber IOL; 4.2% with multifocal IOL). Cataract surgery had been performed in at least one eye for 610 (52.5%) individuals. Higher prevalence of previous cataract surgery correlated (multivariable analysis) with lower IOP (OR: 0.92; 95% CI: 0.88–0.95), glaucomatous optic nerve damage stage (OR: 1.20; 95% CI: 1.05–1.36), and better visual acuity (OR: 0.67; 95% CI: 0.51–0.89). Postoperative best corrected visual acuity was reduced to moderate-to-severe vision impairment (MSVI) in 202 eyes (44.6%; 95% CI: 40.0–49.2) and to blindness in 53 eyes (11.7%; 95% CI: 8.7–14.7). Causes of postoperative MSVI were age-related macular degeneration (AMD) (34.2%), glaucoma (13.9%), and secondary cataract (5.4%). Causes for blindness were AMD (24.5%), glaucoma (18.9%), corneal opacifications (15.8%) and myopic macular degeneration (11.3%). Yttrium Aluminum Garnet-laser capsulotomy had been performed in 6 (1.3%) of 469 right eyes and 12 (2.5%) of 479 left eyes. Prevalence of nuclear cataract and cortical cataract was 604/671 (90.0% in phakic eyes; 51.9% in the whole study population) and 97.9% eyes (48.4% in total study population). Cataract caused bilateral MSVI and blindness in 28.2% (95% CI: 25.6–30) and 2.9% (95% CI: 1.9–3.9), respectively, of all study participants.

Conclusions

Despite a relatively high prevalence of cataract surgery, this multiethnic cohort >85 years of aged from Russia showed a high prevalence of cataract-related MSVI and blindness. Main causes for postoperative MSVI (prevalence: 44.6%) and blindness (prevalence: 11.7%) were AMD, glaucoma, corneal opacifications, and myopic macular degeneration. Almost all individuals aged 85+ years need cataract surgery, despite limited chance of postoperative good vision.

Financial Disclosure(s)

The author(s) have no proprietary or commercial interest in any materials discussed in this article.

目的评估俄罗斯高龄人群中白内障和白内障手术的患病率。方法进行一系列眼科检查。主要结果测量白内障和白内障手术的患病率。469只右眼(41.0%;95%置信区间[CI]:38.1-43.9)和479只左眼(41.6%;95%置信区间[CI]:38.7-44.4)接受了白内障手术(92.1%使用后房型人工晶体;4.7%使用多焦点人工晶体)。610人(52.5%)至少有一只眼睛接受过白内障手术。曾接受白内障手术的比例较高与较低的眼压(OR:0.92;95% CI:0.88-0.95)、青光眼视神经损伤阶段(OR:1.20;95% CI:1.05-1.36)和较好的视力(OR:0.67;95% CI:0.51-0.89)相关(多变量分析)。术后最佳矫正视力下降至中重度视力损伤(MSVI)的有 202 只眼睛(44.6%;95% CI:40.0-49.2),失明的有 53 只眼睛(11.7%;95% CI:8.7-14.7)。导致术后 MSVI 的原因是年龄相关性黄斑变性(AMD)(34.2%)、青光眼(13.9%)和继发性白内障(5.4%)。致盲原因为老年性黄斑变性(AMD)(24.5%)、青光眼(18.9%)、角膜不透明(15.8%)和近视性黄斑变性(11.3%)。在 469 例右眼和 479 例左眼中,分别有 6 例(1.3%)和 12 例(2.5%)进行了钇铝石榴石激光囊袋切开术。核性白内障和皮质性白内障的患病率分别为 604/671 只眼睛(其中 90.0% 患有晶状体白内障,51.9% 患有全眼球白内障)和 97.9% (其中 48.4% 患有全眼球白内障)。白内障导致双侧 MSVI 和失明的比例分别为 28.2% (95% CI: 25.6-30) 和 2.9% (95% CI: 1.9-3.9)。术后 MSVI(发病率:44.6%)和失明(发病率:11.7%)的主要原因是白内障、青光眼、角膜混浊和近视性黄斑变性。尽管术后获得良好视力的机会有限,但几乎所有 85 岁以上的老人都需要接受白内障手术。
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引用次数: 0
The Effect of Glucagon-Like Peptide-1 Receptor Agonists on Diabetic Retinopathy at a Tertiary Care Center GLP-1 受体激动剂对一家三级医疗中心糖尿病视网膜病变的影响
IF 3.2 Q1 OPHTHALMOLOGY Pub Date : 2024-05-06 DOI: 10.1016/j.xops.2024.100547

Objective

The potential association between diabetic retinopathy (DR) worsening and glucagon-like peptide-1 receptor agonists (GLP-1RA) has affected therapeutic management of diabetic patients but remains controversial. This study compared rates of DR development or progression in patients on GLP-1RA to those on SGLT-2 inhibitors (SGLT-2I).

Design

Retrospective cohort study.

Subjects

Nine hundred eighty-one patients with diabetes mellitus taking GLP-1RA or SGLT-2I, the latter serving as controls, between 2012 and 2023.

Methods

Patients were one-to-one greedy matched by propensity scores on race/ethnicity, age, smoking status, baseline body mass index and hemoglobin A1c %, type of diabetes mellitus, baseline DR status and history of DR procedures, duration of drug use, whether they had taken both drug types, and change in hemoglobin A1c % after 1 year on the drug.

Main Outcome Measures

The primary outcome was clinical DR development or progression (termed “worsening”) detected by International Classification of Diseases (ICD), 10th edition codes, confirmed by manual review, on GLP-1RA compared with SGLT-2I after propensity score matching. Secondary outcomes included DR worsening indicated by need for procedures due to complications, and time-to-first DR worsening event.

Results

The study included 692 GLP-1RA users and 289 SGLT-2I users. The mean follow-up periods for GLP-1RA versus SGLT-2I use were 1.54 (standard deviation [SD] 1.82) years and 1.38 (SD 1.56) years, respectively. The rates of clinical worsening were 2.3% and 2.8%, respectively. After propensity score matching, an association was not identified between GLP1-RA and DR worsening neither clinically by ICD-10 codes (odds ratio [OR] = 0.33, 95% confidence interval [CI]: 0.11–1.03) nor by indication for procedures (OR = 0.50, 95% CI 0.13–2.00). Time-to-first DR worsening did not differ between the groups in Kaplan-Meier analysis. The most common type of clinical worsening event for both drug types was vitreous hemorrhage (43.7% and 50% of worsening events in GLP-1RA and SGLT-2I users, respectively). The most common DR procedure indicated was anti-VEGF injections (34% and 35% of GLP-1RA and SGLT-2I events, respectively).

Conclusions

Diabetic retinopathy worsening, either clinically or by procedures, was not associated with GLP-1RA compared with SGLT-2I, both before and after propensity score matching on all analyses, including time-to-first worsening event.

Financial Disclosure(s)

Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

目的糖尿病视网膜病变(DR)恶化与胰高血糖素样肽-1 受体激动剂(GLP-1RA)之间的潜在关联影响了糖尿病患者的治疗管理,但目前仍存在争议。本研究比较了服用 GLP-1RA 和服用 SGLT-2 抑制剂 (SGLT-2I) 患者的 DR 发生率或进展率。方法对患者的种族/民族、年龄、吸烟状况、基线体重指数和血红蛋白A1c%、糖尿病类型、基线DR状况和DR手术史、用药时间、是否同时服用两种药物以及用药1年后血红蛋白A1c%的变化进行倾向得分一对一贪婪匹配。主要结果测量主要结果是与 SGLT-2I 相比,GLP-1RA 与 SGLT-2I 经倾向得分匹配后,通过国际疾病分类 (ICD) 第 10 版代码发现的临床 DR 发展或进展(称为 "恶化"),并通过人工复查确认。次要结果包括因并发症而需要进行手术的DR恶化,以及首次DR恶化事件发生的时间。GLP-1RA 和 SGLT-2I 的平均随访时间分别为 1.54 年(标准差 [SD] 1.82)和 1.38 年(标准差 1.56)。临床恶化率分别为2.3%和2.8%。经过倾向评分匹配后,无论是按 ICD-10 编码(比值比 [OR] = 0.33,95% 置信区间 [CI]:0.11-1.03)还是按手术指征(比值比 [OR] = 0.50,95% 置信区间 [CI]:0.13-2.00),都未发现 GLP1-RA 与 DR 临床恶化之间存在关联。在 Kaplan-Meier 分析中,两组患者的 DR 首次恶化时间没有差异。两种药物最常见的临床恶化事件类型均为玻璃体出血(分别占 GLP-1RA 和 SGLT-2I 使用者恶化事件的 43.7% 和 50%)。结论与SGLT-2I相比,GLP-1RA和SGLT-2I在临床或手术方面的糖尿病视网膜病变恶化与倾向得分匹配前后的所有分析(包括首次恶化事件发生时间)均无关联。
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引用次数: 0
Biological and Methodological Variability in Retinal Nerve Fiber Layer OCT: The Framingham Heart Study 视网膜神经纤维层 OCT 的生物学和方法学变异:弗雷明汉心脏研究
IF 3.2 Q1 OPHTHALMOLOGY Pub Date : 2024-05-06 DOI: 10.1016/j.xops.2024.100549
<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> > 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
目的在以人口为基础的美国老年人样本中,探索与视网膜神经纤维层(RNFL)厚度变异相关的参与者水平生物属性和扫描水平方法属性。方法在单次扫描中对每位参与者的每只眼睛进行三次或三次以上的连续 RNFL 扫描。采用多变量线性混合模型来探讨平均 RNFL 厚度与作为自变量的整个人群和无青光眼自述病史的成人子样本的参与者水平生物属性(年龄、性别、种族、民族和轴长)和扫描水平属性(信号强度 [SS])之间的关系。主要结果测量(1)生物变异性:平均 RNFL 厚度;(2)方法变异性:重复扫描时参与者内部平均 SD。19 微米/年,[95% 置信区间 {CI}:-0.29,-0.09])、女性性别(β = +1.48 微米 vs. 男性,[95% CI:0.09,2.86])、轴向长度(β = -1.24 微米/毫米,[95% CI:-1.80,-0.67])和 SS(β = +1.62 微米/1 单位更大的 SS,[95% CI:1.16,2.09])与 RNFL 厚度显著相关,而种族和民族则不相关(P >;0.05)。在旨在评估方法变异性的分析中,较高的 RNFL 厚度(β = 每增加一微米 +0.02,[95% CI:0.01,0.03])和较低的 SS(β = 每降低一个单位 SS +0.19,[95% CI:0.10,0.27])与较大的 RNFL 变异性显著相关。结论视网膜神经纤维层厚度较低与年龄、性别、轴向长度、SS值较低以及白人(与非裔美国人相比)无青光眼自我报告有关。RNFL厚度越大、SS越低,测量变异性(SD)越高。了解这些生物学和方法学上的变异对帮助解释 OCT 非常重要。
{"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":"&lt;div&gt;&lt;h3&gt;Objective&lt;/h3&gt;&lt;p&gt;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.&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Design&lt;/h3&gt;&lt;p&gt;Cross-sectional analysis using data from the Framingham Heart Study.&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Participants&lt;/h3&gt;&lt;p&gt;One thousand three hundred forty-seven eyes from 825 participants with ≥1 OCT scan and axial length data were included.&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;p&gt;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.&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Main Outcomes Measures&lt;/h3&gt;&lt;p&gt;(1) Biological variability: average RNFL thickness, and (2) methodological variability: average within-participant SD across repeated scans.&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;p&gt;Age (β = &lt;span&gt;&lt;math&gt;&lt;mrow&gt;&lt;mo&gt;−&lt;/mo&gt;&lt;/mrow&gt;&lt;/math&gt;&lt;/span&gt;0.19 microns/year, [95% confidence interval {CI}: &lt;span&gt;&lt;math&gt;&lt;mrow&gt;&lt;mo&gt;−&lt;/mo&gt;&lt;/mrow&gt;&lt;/math&gt;&lt;/span&gt;0.29, &lt;span&gt;&lt;math&gt;&lt;mrow&gt;&lt;mo&gt;−&lt;/mo&gt;&lt;/mrow&gt;&lt;/math&gt;&lt;/span&gt;0.09]), female gender (β = +1.48 microns vs. male, [95% CI: 0.09, 2.86]), axial length (β = &lt;span&gt;&lt;math&gt;&lt;mrow&gt;&lt;mo&gt;−&lt;/mo&gt;&lt;/mrow&gt;&lt;/math&gt;&lt;/span&gt;1.24 microns/mm of greater length, [95% CI: &lt;span&gt;&lt;math&gt;&lt;mrow&gt;&lt;mo&gt;−&lt;/mo&gt;&lt;/mrow&gt;&lt;/math&gt;&lt;/span&gt;1.80, &lt;span&gt;&lt;math&gt;&lt;mrow&gt;&lt;mo&gt;−&lt;/mo&gt;&lt;/mrow&gt;&lt;/math&gt;&lt;/span&gt;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 (&lt;em&gt;P&lt;/em&gt; &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]).&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusions&lt;/h3&gt;&lt;p&gt;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":"4 6","pages":"Article 100549"},"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}
引用次数: 0
Next-Generation Tear Meniscus Height Detecting and Measuring Smartphone-Based Deep Learning Algorithm Leads in Dry Eye Management 基于智能手机深度学习算法的下一代泪液半月板高度检测和测量技术引领干眼症治疗
IF 3.2 Q1 OPHTHALMOLOGY Pub Date : 2024-05-06 DOI: 10.1016/j.xops.2024.100546
Farhad Nejat PhD , Shima Eghtedari MSc , Fatemeh Alimoradi MSc

Purpose

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.

Design

Cross-sectional study using data which was gathered in Vision Health Research Clinic.

Participants

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.

Methods

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).

Main Outcome Measures

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.

Results

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%.

Conclusions

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.

Financial Disclosure(s)

The author(s) have no proprietary or commercial interest in any materials discussed in this article.

目的本研究旨在开发和评估一种基于 Python 深度学习代码的基础架构,用于未来利用智能手机图像对干眼症(DED)进行诊断和管理。方法一位专家使用三星 A71(601 张图片)和 iPhone 11(420 张图片)手机,打开手电筒并直接注视摄像头,捕捉眼睛图像。这些图像只包括一只眼睛(左眼/右眼)的区域。主要结果测量首先,我们的专家对80%的训练数据中的每张眼睛图像分别进行了3次不同的分割。这部分包括眼球、下眼睑和虹膜分割。在自动裁剪下眼睑边缘并放大 8 倍后,在 20% 的测试数据中,将选择适当的泪液半月板高度分割,并使用深度学习算法进行测量。验证数据训练模型的骰子系数为 98.68%,整体模型的准确率为 95.39%。结论看来,该算法有可能预示着未来仅通过智能手机的家庭护理设备诊断和管理 DED 的发展。
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引用次数: 0
An in vitro 3-dimensional Collagen-based Corneal Construct with Innervation Using Human Corneal Cell Lines 利用人体角膜细胞系构建具有神经支配功能的体外三维胶原蛋白角膜结构
IF 3.2 Q1 OPHTHALMOLOGY Pub Date : 2024-05-06 DOI: 10.1016/j.xops.2024.100544

Purpose

To develop a 3-dimensional corneal construct suitable for in vitro studies of disease conditions and therapies.

Design

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.

Results

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.

Conclusions

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.

Financial Disclosure(s)

Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

设计使用化学交联的胶原蛋白和硫酸软骨素细胞外基质创建了体外人类角膜构建体,并将 3 种人类角膜细胞类型(上皮细胞、基质细胞和内皮细胞)与神经细胞一起播种到构建体中。神经细胞来自杂交神经母细胞瘤细胞,其他细胞来自永生化人类角膜细胞系。为了检验构建物的可行性并确定其特征,对构建物进行了细胞毒性、细胞增殖、组织学和蛋白质表达研究。构建体显示出不同细胞层的典型外观,包括健康外观、表型分化的神经元。结论 成功开发了一种体外角膜构建体,其细胞表型保持了解剖学上正确的细胞位置。该构建体可能有助于评估特定的角膜疾病和开发不同的角膜疾病模型。此外,该构建体还可用于评估药物的靶向性和/或对单个角膜层的渗透性,测试角膜疾病的新型疗法,并有可能在研究的早期阶段减少角膜研究中使用动物的必要性。
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引用次数: 0
Factors Associated with Missing Sociodemographic Data in the IRIS® (Intelligent Research in Sight) Registry 与 IRIS®(视线中的智能研究)注册表中社会人口数据缺失有关的因素
IF 3.2 Q1 OPHTHALMOLOGY Pub Date : 2024-04-30 DOI: 10.1016/j.xops.2024.100542
Connor Ross BS , Alexander Ivanov MS , Tobias Elze PhD , Joan W. Miller MD , Flora Lum MD , Alice C. Lorch MD, MPH , Isdin Oke MD, MPH , IRIS® Registry Analytic Center Consortium

Purpose

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.

Design

Cross-sectional study.

Participants

All patients with clinical encounters at practices participating in the IRIS Registry prior to December 31, 2020.

Methods

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.

Main Outcome Measures

Multivariable linear regression was used to describe the association of practice-level characteristics with missing patient-level sociodemographic data.

Results

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 (P < 0.001), cared for a larger nonprivately insured patient population (P = 0.001), and were located in urban areas (P < 0.001). Frequent patient visits were associated with a lower prevalence of missing race (P < 0.001), ethnicity (P < 0.001), and insurance (P < 0.001), but a higher prevalence of missing smoking status (P < 0.001).

Conclusions

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.

Financial Disclosure(s)

Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

目的描述IRIS®(Intelligent Research in Sight)注册表中社会人口学数据缺失的普遍性,并确定与社会人口学数据缺失相关的医疗机构特征。根据患者人数、医生人数、地理位置、患者就诊频率和患者人口统计学特征,对向注册中心提供数据的每家诊所进行了分类。主要结果测量采用多变量线性回归来描述诊所层面特征与患者层面社会人口学数据缺失之间的关联。每家诊所的患者人数中位数为 11 415 人(四分位数间距:5849-24 148),每家诊所的医生人数中位数为 3 人(四分位数间距:1-7)。患者社会人口学数据的缺失率为:出生年份 0.1%、性别 0.4%、种族 24.8%、民族 30.2%、三位数邮政编码 2.3%、州 14.8%、吸烟状况 5.5%、保险类型 17.0%。数据缺失率随着时间的推移而增加,各州的数据缺失率也不尽相同。种族数据缺失与以下情况有关:每位患者就诊次数较少(P <0.001)、非私人保险患者人数较多(P = 0.001)、位于城市地区(P <0.001)。结论IRIS注册表中种族、民族和保险类型数据的缺失存在地理和时间趋势。包括诊所规模、地理位置和患者人数在内的一些诊所层面的特征与社会人口学数据的缺失有关。虽然缺失数据的发生率和模式可能会在未来版本的 IRIS 注册表中发生变化,但仍有必要制定标准化方法,以最大限度地减少潜在的偏差来源,并确保各项研究的可重复性。
{"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":"4 6","pages":"Article 100542"},"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}
引用次数: 0
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 CONNECTDROP®是一种与智能手机应用程序配对的用药事件监测系统插件,青光眼患者是否能接受它来服用日常药物?CONDORE 试点研究
IF 3.2 Q1 OPHTHALMOLOGY Pub Date : 2024-04-30 DOI: 10.1016/j.xops.2024.100541
Jean-Baptiste Dériot MD, Emmanuelle Albertini MD

Objective

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.

Design

A single-center, single-arm, prospective interventional pilot study (NCT04552964).

Participants

Adults with glaucoma managed with at least a fixed combination of timolol/dorzolamide who are adherent to treatment.

Methods

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.

Main Outcome Measures

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.

Results

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.

Conclusion

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.

Financial Disclosure(s)

The authors have no proprietary or commercial interest in any materials discussed in this article.

目的这项试验性研究测试了未来疗效试验的可行性,该试验将考察CONNECTDROP®(一种新型用药事件监测系统(MEMS)与移动医疗应用程序的组合)对青光眼患者坚持用药的影响。方法向参与者(n = 31)提供 MEMS 设备和安装了应用程序的智能手机。参与者(31 人)将获得 MEMS 设备和安装了应用软件的智能手机,他们必须在 9 周内使用 MEMS,并按处方服用噻吗洛尔/多佐胺。第 9 周结束时为研究终点,届时所有研究材料均已归还,参与者填写了一份包含 17 个项目的患者满意度问卷。对每个 MEMS 在 9 周内连续收集的数据进行了分析,以确定这些数据是否适用于量化单个参与者的依从性以及研究队列中的依从性趋势。在基线、第 8 周和第 9 周收集临床数据,以进行安全性评估。次要结果测量包括参与者对处理 MEMS 及其可用性的反馈,以及对连接应用程序的反馈。客观数据用于确定参与者的用药依从性。结果MEMS连接设备在9周后获得了74.1%的总体满意度。此外,70.4% 的参与者认为 MEMS 易于使用。然而,只有 59.2% 的人表示移动医疗应用的反馈有助于提醒他们进行治疗。MEMS 导出的数据显示,8 周后,70.4% 的参与者的 "依从性评分 "达到 80% 或以上,完成研究的 40.7% 的参与者没有正确更换药瓶。结论在这项试点研究中,CONNECTDROP 设备能够在 2 个月内监测抗青光眼药物的每日摄入量,在这批患者中满意度很高,而且易于使用。获得的客观依从性数据似乎是可靠的,但必须经过验证才能用于疗效试验。
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引用次数: 0
Highly Accurate and Precise Automated Cup-to-Disc Ratio Quantification for Glaucoma Screening 用于青光眼筛查的高精度杯盘比自动定量法
IF 3.2 Q1 OPHTHALMOLOGY Pub Date : 2024-04-27 DOI: 10.1016/j.xops.2024.100540
Abadh K. Chaurasia MOptom , Connor J. Greatbatch MBBS , Xikun Han PhD , Puya Gharahkhani PhD , David A. Mackey MD, FRANZCO , Stuart MacGregor PhD , Jamie E. Craig MBBS, PhD , Alex W. Hewitt MBBS, FRANZCO, PhD

Objective

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.

Design

Algorithm development for estimating CDR using fundus data from a population-based observational study.

Participants

A total of 181 768 fundus images from the United Kingdom Biobank (UKBB), Drishti_GS, and EyePACS.

Methods

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.

Main Outcome Measures

The area under the receiver operating characteristic curve and coefficient of determination.

Results

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.

Conclusions

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.

Financial Disclosure(s)

Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

目的 杯盘比(CDR)增大是青光眼性视神经病变的标志。与自动方法相比,人工评估 CDR 的准确性可能较低,而且更耗时。方法使用FastAI和PyTorch库在英国生物库(UKBB)、Drishti_GS和EyePACS的眼底图像上训练基于卷积神经网络的模型。建立的模型用于确定图像的渐变性(分类分析)以及估计 CDR(回归分析)。结果我们的梯度模型 vgg19_batch normalization (bn) 在 16 045 张图像的验证集上达到了 97.13% 的准确率,准确率为 99.26%,接收器操作特征曲线下的面积为 96.56%。通过回归分析,我们的最佳模型(在 vgg19_bn 架构上训练)在确定 CDR 的 12 183 张验证集上的决定系数为 0.8514(95% 置信区间 [CI]:0.8459-0.8568),平均平方误差为 0.0050(95% CI:0.0048-0.0051),平均绝对误差为 0.0551(95% CI:0.0543-0.0559)。回归点被转换成分类指标,20 个类别的容差为 0.2;分类指标的准确率达到 99.20%。然后使用 EyePACS 数据集(98 172 个健康数据集,3270 个青光眼数据集)对青光眼分类模型进行外部验证,准确率、灵敏度和特异性分别为 82.49%、72.02% 和 82.83%。虽然我们的人工智能CDR估计值达到了很高的准确度,但青光眼筛查的CDR阈值会因其他临床参数的不同而有所差异。
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引用次数: 0
Liquid Biopsy for Proliferative Diabetic Retinopathy: Single-Cell Transcriptomics of Human Vitreous Reveals Inflammatory T-Cell Signature 用于增殖性糖尿病视网膜病变的液体活检:人类玻璃体单细胞转录组学揭示炎性 T 细胞特征
IF 3.2 Q1 OPHTHALMOLOGY Pub Date : 2024-04-26 DOI: 10.1016/j.xops.2024.100539
Rachana Haliyur MD, PhD , David H. Parkinson MS , Feiyang Ma PhD , Jing Xu PhD , Qiang Li MD, PhD , Yuanhao Huang , Lam C. Tsoi PhD , Rachael Bogle MS , Jie Liu PhD , Johann E. Gudjonsson MD , Rajesh C. Rao MD

Purpose

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.

Design

Case series.

Subjects

Vitreous and peripheral blood obtained from 5 adult patients (6 eyes) undergoing pars plana vitrectomy for vision-threatening PDR.

Methods

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.

Main Outcome Measures

Single-cell transcriptomic profiles of vitreous and peripheral blood.

Results

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 (CD2, CD3D, CD3E, and GZMA), B cells (CD79A, IGHM, MS4A1 (CD20), and HLA-DRA), myeloid cells (LYZ, CST3, AIF1, and IFI30), and neutrophils (BASP1, CXCR2, S100A8, and S100A9). 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.

Conclusions

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.

Financial Disclosure(s)

Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

目的目前治疗增殖性糖尿病视网膜病变(PDR)的疗法并不专门针对不依赖血管内皮生长因子的细胞类型特异性过程,这些过程会导致视力丧失,如炎症通路。本研究旨在通过阐明PDR患者玻璃体内的单细胞情况,确定可靶向的细胞类型和相应的信号通路。设计病例系列。研究对象5名因视力受到威胁而接受玻璃体旁切除术的成年患者(6只眼)的玻璃体和外周血。方法对 6 只眼睛玻璃体切除术中稀释盒洗液中获得的玻璃体细胞和外周血单核细胞(PBMC,n = 5)进行单细胞 RNA 测序(scRNA-seq)。使用 Chromium 10x 平台进行了基于液滴的 scRNA-seq,以获得单细胞转录组。主要结果测量玻璃体和外周血的单细胞转录组图谱。结果纳入了 13 675 个手术采集的玻璃体细胞和 22 636 个 PBMC 的转录组。聚类结果显示,所有眼球中始终存在 4 种细胞状态,具有代表性的转录本包括 T 细胞(CD2、CD3D、CD3E 和 GZMA)、B 细胞(CD79A、IGHM、MS4A1 (CD20) 和 HLA-DRA)、骨髓细胞(LYZ、CST3、AIF1 和 IFI30)和中性粒细胞(BASP1、CXCR2、S100A8 和 S100A9)。与外周血(46.2%)不同,玻璃体内的大多数细胞是 T 细胞(91.6%),而玻璃体内基本上没有中性粒细胞。玻璃体内存在全套的适应性 T 细胞,包括 CD4+、CD8+ 和 T 调节细胞(Treg)以及先天性免疫系统效应因子(即自然杀伤 T 细胞)。结论在首次对疾病状态下的人类玻璃体内进行的单细胞转录组学表征中,我们发现PDR玻璃体内主要由T细胞组成,T细胞是适应性免疫的重要组成部分,其活性和比例与外周血中的T细胞不同,而且中性粒细胞基本上不存在。这些结果表明,通过收集玻璃体切除术中原本被丢弃的稀释盒洗液来进行玻璃体液体活检是可行的,可以获得人类玻璃体视网膜疾病的机理和治疗见解。
{"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":"4 6","pages":"Article 100539"},"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}
引用次数: 0
Contributions of Lipid-Related Metabolites and Complement Proteins to Early and Intermediate Age-Related Macular Degeneration 脂质相关代谢物和补体蛋白对早期和中期老年性黄斑变性的影响
IF 3.2 Q1 OPHTHALMOLOGY Pub Date : 2024-04-26 DOI: 10.1016/j.xops.2024.100538
Simon Nusinovici PhD , Lei Zhou PhD , Xinyue Wang MS , Yih Chung Tham PhD , Xiaomeng Wang PhD , Tien Yin Wong MD, PhD , Usha Chakravarthy MD, PhD , Ching-Yu Cheng MD, PhD

Objective

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.

Design

Nested case–control study.

Subjects and Controls

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.

Methods

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.

Main Outcome Measures

Age-related macular degeneration was classified using the Beckman classification system.

Results

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 ORintermediate = 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 (ORearly = 1.58; 95% CI, 1.08–2.30 and ORintermediate = 1.56; 95% CI, 1.04–2.34). C6 was positively (ORearly = 1.41; 95% CI, 1.03–1.93) associated with early AMD. However, IC1 was negatively associated with early AMD (ORearly = 0.62; 95% CI, 0.38–0.99), whereas C1QC (ORintermediate = 0.63; 95% CI, 0.42–0.93) and FHR1 (ORintermediate = 0.73; 95% CI, 0.54–0.98) were both negatively associated with intermediate AMD.

Conclusions

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.

Financial Disclosure(s)

The authors have no proprietary or commercial interest in any materials discussed in this article.

目标我们的目标是通过整合代谢组学和蛋白质组学数据,利用机器学习模型确定脂质和补体蛋白对早期和中期年龄相关性黄斑变性(AMD)的影响。在 6753 名参与者中,我们随机选取了 155 例印度裔和 155 例华裔 AMD 患者,并与 310 名对照者进行了年龄、性别和种族配对。我们首先使用随机森林模型选出了对早期和中期 AMD 最有贡献的脂质和补体蛋白。结果在 310 名 AMD 患者中,166 人(53.5%)患有早期 AMD,144 人(46.5%)患有中期 AMD。首先,高密度脂蛋白(HDL)颗粒直径与早期和中期 AMD 呈正相关(HDL 直径每增加 1 个标准差,早期的几率比 [OR] = 1.69;95% 置信区间 [CI],1.11-2.55;中期的几率比 [OR] = 1.72;95% 置信区间,1.11-2.66)。其次,补体蛋白 2(C2)、补体 C1 抑制剂(IC1)、补体蛋白 6(C6)、补体蛋白 1QC (C1QC)和补体因子 H 相关蛋白 1(FHR1)与 AMD 相关。C2与早期和中期AMD均呈正相关(早期OR=1.58;95% CI,1.08-2.30;中期OR=1.56;95% CI,1.04-2.34)。C6 与早期 AMD 呈正相关(ORearly = 1.41;95% CI,1.03-1.93)。然而,IC1 与早期 AMD 呈负相关(ORearly = 0.62;95% CI,0.38-0.99),而 C1QC(ORintermediate = 0.63;95% CI,0.42-0.93)和 FHR1(ORintermediate = 0.73;95% CI,0.54-0.98)均与早期 AMD 呈负相关。结论虽然高密度脂蛋白直径和 C2 水平与早期和中期 AMD 都有关联,但 IC1、C6、C1QC 和 FHR1 的失调仅在 AMD 的特定阶段才被观察到。这些发现强调了AMD中补体系统失调的复杂性,它似乎因疾病的严重程度而异。
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引用次数: 0
期刊
Ophthalmology science
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