Ophthalmology science最新文献_第6页

Ocular Adverse Events Following Coronavirus Disease 2019 Infection: A Self-controlled Case Series Study from the Entire Korean Population 2019年冠状病毒病感染后的眼部不良事件：来自韩国全体人口的自控病例系列研究

IF 3.2 Q1 OPHTHALMOLOGY

Ophthalmology science

Pub Date : 2024-10-26 DOI: 10.1016/j.xops.2024.100638

Sungsoon Hwang MD, PhD , Se Woong Kang MD, PhD , Jaehwan Choi MD , Kyung-Ah Park MD, PhD , Dong Hui Lim MD, PhD , Ju-Young Shin PhD , Danbee Kang PhD , Juhee Cho PhD , Sang Jin Kim MD, PhD

Purpose

This study aimed to assess the risk of ocular adverse events, including retinal artery occlusion (RAO), retinal vein occlusion (RVO), noninfectious uveitis (NIU), noninfectious scleritis (NIS), optic neuritis (ON), ischemic optic neuropathy (ION), and ocular motor cranial nerve palsy (OMCNP), after coronavirus disease 2019 (COVID-19) infection.

Design

Population-based self-controlled case series (SCCS).

Participants

The study included patients from the entire Korean population of 52 million who experienced incident RAO, RVO, anterior NIU, nonanterior NIU, NIS, ON, ION, or OMCNP between January 1, 2021, and October 29, 2022.

Methods

This nationwide SCCS utilized data from the Korea National Health Insurance Service and the Korea Disease Control and Prevention Agency. The risk period after infection was defined as up to 24 weeks after COVID-19 infection. Conditional Poisson regression was used to calculate the relative incidence rate ratios (IRRs) for RAO, RVO, anterior NIU, nonanterior NIU, NIS, ON, ION, and OMCNP during the designated risk periods.

Main Outcome Measures

The IRRs for RAO, RVO, anterior NIU, nonanterior NIU, NIS, ON, ION, and OMCNP during the risk periods.

Results

The study included 9336, 103 362, 201 010, 25 428, 23 744, 3026, 69 933, and 16 335 cases of incident RAO, RVO, anterior NIU, nonanterior NIU, NIS, ON, ION, and OMCNP, respectively. The IRRs (95% confidence interval) during the early risk period (1–8 weeks) were 0.94 (0.83–1.07), 1.01 (0.97–1.04), 1.00 (0.98–1.03), 0.96 (0.90–1.03), 1.00 (0.94–1.07), 0.97 (0.81–1.17), 0.97 (0.93–1.01), and 1.02 (0.94–1.11), respectively. In the late risk period (9–24 weeks), the IRRs were 1.02 (0.92–1.12), 1.01 (0.98–1.04), 1.01 (0.99–1.03), 1.02 (0.97–1.08), 1.02 (0.97–1.08), 0.99 (0.85–1.15), 1.02 (0.99–1.06), and 0.97 (0.90–1.03), respectively. Stratified analyses showed that in patients with a history of cerebro-cardiovascular disease, the risk of RAO increased during the late risk period, with an IRR (95% confidence interval) of 1.19 (1.02–1.40).

Conclusions

The risk of incident RVO, anterior NIU, nonanterior NIU, NIS, ON, ION, or OMCNP did not increase after COVID-19 infection. The risk of incident RAO increased only in individuals with preexisting cardio-cerebrovascular disease.

Financial Disclosure(s)

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

目的本研究旨在评估2019年冠状病毒病（COVID-19）感染后发生眼部不良事件的风险，包括视网膜动脉闭塞（RAO）、视网膜静脉闭塞（RVO）、非感染性葡萄膜炎（NIU）、非感染性巩膜炎（NIS）、视神经炎（ON）、缺血性视神经病变（ION）和眼部运动性颅神经麻痹（OMCNP）。设计基于人群的自我对照病例系列研究（SCCS）。方法这项全国范围的 SCCS 研究利用了韩国国民健康保险服务局和韩国疾病预防控制机构提供的数据。感染后的风险期定义为感染 COVID-19 后的 24 周内。采用条件泊松回归法计算指定风险期内RAO、RVO、前NIU、非前NIU、NIS、ON、ION和OMCNP的相对发病率比（IRRs）。主要结果测量风险期内RAO、RVO、前NIU、非前NIU、NIS、ON、ION和OMCNP的IRR。早期风险期（1-8 周）的内部收益率（95% 置信区间）分别为 0.94（0.83-1.07）、1.01（0.97-1.04）、1.00（0.98-1.03）、0.96（0.90-1.03）、1.00（0.94-1.07）、0.97（0.81-1.17）、0.97（0.93-1.01）和 1.02（0.94-1.11）。在风险晚期（9-24 周），IRR 分别为 1.02（0.92-1.12）、1.01（0.98-1.04）、1.01（0.99-1.03）、1.02（0.97-1.08）、1.02（0.97-1.08）、0.99（0.85-1.15）、1.02（0.99-1.06）和 0.97（0.90-1.03）。结论感染 COVID-19 后，发生 RVO、前 NIU、非前 NIU、NIS、ON、ION 或 OMCNP 的风险并未增加。只有存在心脑血管疾病的个体发生RAO的风险才会增加。

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引用次数: 0

Deep Learning to Predict the Future Growth of Geographic Atrophy from Fundus Autofluorescence 基于眼底自体荧光的深度学习预测地理萎缩的未来增长。

IF 3.2 Q1 OPHTHALMOLOGY

Ophthalmology science

Pub Date : 2024-10-23 DOI: 10.1016/j.xops.2024.100635

Anish Salvi MS , Julia Cluceru PhD , Simon S. Gao PhD , Christina Rabe PhD , Courtney Schiffman PhD , Qi Yang PhD , Aaron Y. Lee MD, MSCI , Pearse A. Keane MD, FRCOphth , Srinivas R. Sadda MD , Frank G. Holz MD , Daniela Ferrara MD, PhD , Neha Anegondi MTech

Purpose

The region of growth (ROG) of geographic atrophy (GA) throughout the macular area has an impact on visual outcomes. Here, we developed multiple deep learning models to predict the 1-year ROG of GA lesions using fundus autofluorescence (FAF) images.

Design

In this retrospective analysis, 3 types of models were developed using FAF images collected 6 months after baseline to predict the GA lesion area (segmented lesion mask) at 1.5 years, FAF images collected at baseline and 6 months to predict the GA lesion at 1.5 years, and FAF images collected 6 months after baseline to predict the GA lesion at 1 and 1.5 years. The 1-year ROG from the 6-month visit was derived by taking the difference between the GA lesion area (segmented lesion mask) at the 1.5-year and 6-month visits.

Participants

Patients enrolled in the following lampalizumab clinical trials and prospective observational studies: NCT02247479, NCT02247531, NCT02479386, and NCT02399072.

Methods

Datasets of study eyes from 597 patients were split into model training (310), validation (78), and test sets (209), stratified by baseline or initial lesion area, lesion growth rate, foveal involvement, and focality. Deep learning experiments were performed using the 2-dimensional U-Net; whole-lesion and multiclass models were developed.

Main Outcome Measures

The performance of the models was evaluated by calculating the Dice score, coefficient of determination (R²), and the squared Pearson correlation coefficient (r²) between the true and derived GA lesion 1-year ROG.

Results

The model using baseline and 6-month FAF images to predict GA lesion enlargement at 1.5 years had the best performance for the derived 1-year ROG. Mean Dice scores were 0.73, 0.68, and 0.70 in the training, validation, and test sets, respectively. The R² (0.77, 0.53, and 0.79) and r² (0.83, 0.61, and 0.79) showed similar trends across the 3 sets.

Conclusions

These findings show the potential of using baseline and/or 6-month visit FAF images to predict 1-year GA ROG using a deep learning approach. This work could potentially help support decision-making in clinical trials and more informed treatment decisions in clinical practice.

Financial Disclosure(s)

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

目的：地理萎缩（GA）的生长区域（ROG）遍及黄斑区域，影响视力结果。在这里，我们开发了多个深度学习模型，利用眼底自身荧光（FAF）图像预测GA病变1年的ROG。设计：在本回顾性分析中，采用基线后6个月收集的FAF图像来预测1.5年的GA病变面积（分段病变遮罩），基线后6个月收集的FAF图像来预测1.5年的GA病变，基线后6个月收集的FAF图像来预测1年和1.5年的GA病变，建立了3种模型。6个月随访后的1年ROG是通过1.5年和6个月随访时GA病变面积（分段病变掩膜）的差异得出的。参与者：纳入以下lampalizumab临床试验和前瞻性观察性研究的患者：NCT02247479， NCT02247531， NCT02479386和NCT02399072。方法：来自597例患者的研究眼数据集被分为模型训练集（310）、验证集（78）和测试集（209），并按基线或初始病变面积、病变生长速度、中央凹受累程度和焦点进行分层。采用二维U-Net进行深度学习实验；建立了全病变模型和多级模型。主要结局指标：通过计算Dice评分、决定系数（R2）以及真实和衍生GA病变1年ROG之间的Pearson相关系数（R2）的平方来评估模型的性能。结果：使用基线和6个月FAF图像预测1.5年时GA病变扩大的模型对衍生的1年ROG具有最佳性能。在训练集、验证集和测试集中，平均Dice得分分别为0.73、0.68和0.70。3组间的R2（0.77、0.53、0.79）和R2（0.83、0.61、0.79）的变化趋势相似。结论：这些发现表明使用基线和/或6个月就诊FAF图像使用深度学习方法预测1年GA ROG的潜力。这项工作可能有助于支持临床试验中的决策，并在临床实践中做出更明智的治疗决策。财务披露：专有或商业披露可在本文末尾的脚注和披露中找到。

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引用次数: 0

Substance P- and Insulin-like Growth Factor 1-derived Tetrapeptides for Neurotrophic Keratopathy Related to Leprosy: A Clinical Trial P物质和胰岛素样生长因子1衍生的四肽治疗与麻风病相关的神经营养性角膜病变：一项临床试验

IF 3.2 Q1 OPHTHALMOLOGY

Ophthalmology science

Pub Date : 2024-10-21 DOI: 10.1016/j.xops.2024.100634

Shoko Kondo MD , Yoshiko Okano MD, PhD , Satoshi Iraha MD, PhD , Shoji Tokunaga PhD

Purpose

Neurotrophic keratopathy is part of the leprosy sequelae and causes progressive deterioration of visual acuity. Although leprosy is bacteriologically curable, there is currently no efficient treatment. Eye drops containing tetrapeptides, phenylalanine-glycine-leucine-methionine-amide (FGLM-NH₂) and serine-serine-serine-arginine (SSSR), derived from substance P and insulin-like growth factor 1, are clinically efficacious in the treatment of corneal epithelial disorders caused by neurotrophic keratopathy. To further investigate the effect of this treatment on leprosy sequalae, we evaluated the clinical efficacy of FGLM-NH₂+SSSR eye drops for treating neurotrophic keratopathy.

Design

Clinical trial: interventional, multicenter, exploratory, single-arm, before and after comparison.

Participants

The eyes (12) of 11 patients, aged >60 years, were studied from 2 leprosy sanatoriums in Japan.

Methods

Patients with neurotrophic keratopathy in leprosy sanatorium, specifically those with corneal perception of <40 mm, assessed by the Cochet-Bonnet corneal esthesiometer, and persistent corneal epithelial defects (PEDs) or corneal stromal thinning, or both, were included in this study. Those treated for infection in the acute phase were excluded from the study. Eye drops containing FGLM-NH₂ 0.05% and SSSR 5 × 10^-6% were administered 4 times daily for up to 3 months. Fluorescein staining and optical corneal sections were photographed using a slit lamp microscope at protocol-set intervals. Where possible, anterior segment OCT was performed before and after the intervention.

Main Outcome Measures

The primary outcome measured was improvement in neurotrophic keratopathy. The patient was judged to have improved when ≥1 of the following criteria were met: (1) healing epithelial defects or (2) increased thickness in the thin area of the cornea. Secondary end points were visual acuity, subjective findings, and time to complete healing for a PED.

Results

Neurotrophic keratopathy on epithelial defects or stromal thickness improved in 83.3% of the patients (90% confidence interval 56.2%–97.0%, P < 0.00001). The mean value of corrected visual acuity increased −0.16 by logarithm of the minimum angle of resolution. There were no adverse events reported in association with the treatment.

Conclusions

We confirmed that FGLM-NH₂+SSSR eye drops are effective for neurotrophic keratopathy without any adverse reaction in leprosy. These results should be disseminated to any parties who could need this information.

Financial Disclosure(s)

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

目的：神经营养性角膜病变是麻风病后遗症的一部分，导致视力进行性恶化。虽然麻风病在细菌学上是可以治愈的，但目前还没有有效的治疗方法。含有P物质衍生的苯丙氨酸-甘氨酸-亮氨酸-蛋氨酸-酰胺（FGLM-NH2）和丝氨酸-丝氨酸-丝氨酸-精氨酸（SSSR）四肽滴眼液和胰岛素样生长因子1在临床上治疗神经营养性角膜病变引起的角膜上皮疾病是有效的。为了进一步探讨这种治疗对麻风后遗症的影响，我们评估了FGLM-NH2+SSSR滴眼液治疗神经营养性角膜病变的临床疗效。设计：临床试验：介入性、多中心、探索性、单臂、前后比较。研究对象：来自日本两家麻风病疗养院的11名患者的眼睛（12），年龄在50 ~ 60岁之间。方法：麻风疗养院神经营养性角膜病变患者，特别是角膜感知为2 0.05%，SSSR为5 × 10-6%的患者，每天给药4次，持续3个月。荧光素染色和光学角膜切片在协议设定的间隔使用裂隙灯显微镜拍摄。在可能的情况下，在干预前后进行前段OCT检查。主要观察指标：主要观察指标为神经营养性角膜病变的改善。当满足以下标准≥1项时，判断患者改善：(1)上皮缺损愈合或(2)角膜薄区厚度增加。次要终点是视力、主观表现和PED的完全愈合时间。结果：83.3%的神经营养性角膜病变患者上皮缺损或间质厚度改善（90%可信区间56.2% ~ 97.0%，P）。结论：我们证实FGLM-NH2+SSSR滴眼液对麻风病神经营养性角膜病变有效，无不良反应。这些结果应散发给任何可能需要这些资料的各方。财务披露：专有或商业披露可在本文末尾的脚注和披露中找到。

{"title":"Substance P- and Insulin-like Growth Factor 1-derived Tetrapeptides for Neurotrophic Keratopathy Related to Leprosy: A Clinical Trial","authors":"Shoko Kondo MD , Yoshiko Okano MD, PhD , Satoshi Iraha MD, PhD , Shoji Tokunaga PhD","doi":"10.1016/j.xops.2024.100634","DOIUrl":"10.1016/j.xops.2024.100634","url":null,"abstract":"<div><h3>Purpose</h3><div>Neurotrophic keratopathy is part of the leprosy sequelae and causes progressive deterioration of visual acuity. Although leprosy is bacteriologically curable, there is currently no efficient treatment. Eye drops containing tetrapeptides, phenylalanine-glycine-leucine-methionine-amide (FGLM-NH<sub>2</sub>) and serine-serine-serine-arginine (SSSR), derived from substance P and insulin-like growth factor 1, are clinically efficacious in the treatment of corneal epithelial disorders caused by neurotrophic keratopathy. To further investigate the effect of this treatment on leprosy sequalae, we evaluated the clinical efficacy of FGLM-NH<sub>2</sub>+SSSR eye drops for treating neurotrophic keratopathy.</div></div><div><h3>Design</h3><div>Clinical trial: interventional, multicenter, exploratory, single-arm, before and after comparison.</div></div><div><h3>Participants</h3><div>The eyes (12) of 11 patients, aged >60 years, were studied from 2 leprosy sanatoriums in Japan.</div></div><div><h3>Methods</h3><div>Patients with neurotrophic keratopathy in leprosy sanatorium, specifically those with corneal perception of <40 mm, assessed by the Cochet-Bonnet corneal esthesiometer, and persistent corneal epithelial defects (PEDs) or corneal stromal thinning, or both, were included in this study. Those treated for infection in the acute phase were excluded from the study. Eye drops containing FGLM-NH<sub>2</sub> 0.05% and SSSR 5 × 10<sup>-6</sup>% were administered 4 times daily for up to 3 months. Fluorescein staining and optical corneal sections were photographed using a slit lamp microscope at protocol-set intervals. Where possible, anterior segment OCT was performed before and after the intervention.</div></div><div><h3>Main Outcome Measures</h3><div>The primary outcome measured was improvement in neurotrophic keratopathy. The patient was judged to have improved when ≥1 of the following criteria were met: (1) healing epithelial defects or (2) increased thickness in the thin area of the cornea. Secondary end points were visual acuity, subjective findings, and time to complete healing for a PED.</div></div><div><h3>Results</h3><div>Neurotrophic keratopathy on epithelial defects or stromal thickness improved in 83.3% of the patients (90% confidence interval 56.2%–97.0%, <em>P</em> < 0.00001). The mean value of corrected visual acuity increased −0.16 by logarithm of the minimum angle of resolution. There were no adverse events reported in association with the treatment.</div></div><div><h3>Conclusions</h3><div>We confirmed that FGLM-NH<sub>2</sub>+SSSR eye drops are effective for neurotrophic keratopathy without any adverse reaction in leprosy. These results should be disseminated to any parties who could need this information.</div></div><div><h3>Financial Disclosure(s)</h3><div>Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.</div></div>","PeriodicalId":74363,"journal":{"name":"Ophthalmology science","volume":"5 2","pages":"Article 100634"},"PeriodicalIF":3.2,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11665617/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142883875","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

Comparison between Spectral-domain and Swept-source OCT Angiography Scans for the Measurement of Hyperreflective Foci in Age-related Macular Degeneration 光谱域与扫描源OCT血管造影测量老年性黄斑变性高反射病灶的比较。

IF 3.2 Q1 OPHTHALMOLOGY

Ophthalmology science

Pub Date : 2024-10-21 DOI: 10.1016/j.xops.2024.100633

Gissel Herrera MD , Yuxuan Cheng PhD , Yamini Attiku MD , Farhan E. Hiya MD , Mengxi Shen MD, PhD , Jeremy Liu MD , Jie Lu PhD , Alessandro Berni MD , Omer Trivizki MD , Jianqing Li MD , Robert C. O’Brien PhD , Giovanni Gregori PhD , Ruikang K. Wang PhD , Philip J. Rosenfeld MD, PhD

Purpose

Spectral-domain OCT angiography (SD-OCTA) scans were used in an algorithm developed for swept-source OCT angiography (SS-OCTA) scans to determine if SD-OCTA scans yielded similar results for the measurement of hyperreflective foci (HRF) in intermediate age-related macular degeneration (iAMD).

Design

Retrospective study.

Participants

Forty eyes from 35 patients with iAMD.

Methods

Patients underwent SD-OCTA and SS-OCTA imaging at the same visit using a 6 × 6 mm OCTA scan pattern. Hyperreflective foci were detected as hypotransmission defects on en face structural images generated from a custom slab positioned 64 to 400 μm beneath Bruch’s membrane and confirmed on corresponding B-scans by the presence of well circumscribed lesions within the neurosensory retina or along the retinal pigment epithelium (RPE) that are of equal or greater reflectivity than that of the RPE. Two independent graders evaluated the en face images and B-scans for the presence of these lesions. Outlines of HRF on en face images were generated using a published semiautomated algorithm developed for SS-OCTA scans and manually corrected by the graders when necessary. The total area measurements of the HRF within the 5-mm circle centered on the fovea were obtained from the algorithm using each imaging method.

Main Outcome Measures

Agreement of the square root (sqrt) of the HRF total areas obtained from SS-OCTA and SD-OCTA.

Results

The sqrt total areas of the HRF from both imaging modalities were highly concordant, with Lin’s concordance correlation coefficient (r_c) of 0.94 (95% confidence interval: 0.86–0.97; P < 0.001). The mean sqrt of the total HRF area measurements identified using SS-OCTA and SD-OCTA imaging were 0.390 mm (standard deviation [SD]: 0.170) and 0.393 mm (SD: 0.187), respectively with mean difference of −0.003 (95% confidence interval: −0.021 to 0.015; P=0.76).

Conclusions

Spectral-domain OCT angiography scans yielded results similar to SS-OCTA scans when the same semiautomated algorithm was used to measure HRF in the central 5 mm of the macula, suggesting that either a single 6 × 6 mm SD-OCTA or a SS-OCTA scan pattern can be used to determine the total macular HRF burden in eyes with age-related macular degeneration.

Financial Disclosure(s)

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

目的：光谱域OCT血管造影（SD-OCTA）扫描用于扫描源OCT血管造影（SS-OCTA）扫描的算法，以确定SD-OCTA扫描是否产生类似的结果，用于测量中度年龄相关性黄斑变性（iAMD）的高反射灶（HRF）。设计：回顾性研究。参与者：35例iAMD患者的40只眼睛。方法：患者同时行6 × 6 mm OCTA扫描模式的SD-OCTA和SS-OCTA成像。在Bruch膜下64 ~ 400 μm的定制板上生成的正面结构图像上检测到高反射灶为低透射缺陷，并在相应的b扫描上通过在神经感觉视网膜内或沿视网膜色素上皮（RPE）存在边界良好的病变来证实，这些病变的反射率等于或大于RPE。两名独立评分者评估正面图像和b片是否存在这些病变。人脸图像上的HRF轮廓是使用已发布的用于SS-OCTA扫描的半自动算法生成的，并在必要时由评分员手动校正。采用各成像方法，通过算法获得以中央凹为中心的5mm圆内HRF的总面积测量值。主要观察指标：SS-OCTA和SD-OCTA获得的HRF总面积的平方根（sqrt）一致性。结果：两种成像方式的HRF的sqrt总面积高度一致，Lin’s一致性相关系数（rc）为0.94(95%可信区间：0.86-0.97；P P = 0.76)。结论：当使用相同的半自动算法测量黄斑中心5mm的HRF时，光谱域OCT血管造影扫描的结果与SS-OCTA扫描的结果相似，这表明单个6 × 6 mm的SD-OCTA或SS-OCTA扫描模式可用于确定年龄相关性黄斑变性眼睛的黄斑总HRF负担。财务披露：专有或商业披露可在本文末尾的脚注和披露中找到。

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引用次数: 0

Progression of Capillary Hypoperfusion in Advanced Stages of Nonproliferative Diabetic Retinopathy: 6-month Analysis of RICHARD Study 非增生性糖尿病视网膜病变晚期毛细血管灌注不足的进展：RICHARD 研究的 6 个月分析

IF 3.2 Q1 OPHTHALMOLOGY

Ophthalmology science

Pub Date : 2024-10-16 DOI: 10.1016/j.xops.2024.100632

Inês Pereira Marques MD, PhD , Débora Reste-Ferreira MSc , Torcato Santos , Luís Mendes PhD , António Cunha-Vaz Martinho MD , Taffeta Ching Ning Yamaguchi PhD , Ana Rita Santos PhD , Elizabeth Pearce PhD , José Cunha-Vaz MD, PhD

Purpose

To evaluate the 6-month progression of retinal capillary perfusion in eyes with advanced stages of nonproliferative diabetic retinopathy (NPDR).

Design

RICHARD (NCT05112445), 2-year prospective longitudinal study.

Participants

Sixty eyes with Diabetic Retinopathy Severity Scale (DRSS) levels 43, 47, and 53 from 60 patients with type 2 diabetes. Fifty-one patients completed the 6-month evaluation.

Methods

Eyes were evaluated on Optos California (Optos plc) ultrawidefield fundus fluorescein angiography (UWF-FFA), swept-source OCT angiography (SS-OCTA) (PLEX Elite 9000, ZEISS) and spectral-domain OCTA (SD-OCTA) (CIRRUS HD-OCT 5000 Angioplex, ZEISS). DRSS classification was performed based on 7-field color fundus photographs (CFPs) complemented with Optos California UWF-fundus imaging.

Main Outcome Measures

Ischemic index was obtained from Optos. Vascular quantification metrics, namely foveal avascular zone, skeletonized vessel density (SVD), and perfusion density (PD) metrics, were acquired on OCTA in the superficial and deep capillary plexuses (SCP and DCP). Microaneurysm assessment was automatically performed based on CFP images using the RetmarkerDR (Retmarker SA, Meteda Group).

Results

Swept-source-OCTA metrics showed statistically significant differences between the advanced stages of NPDR. Differences between DRSS levels 47 and 53 were found at baseline in the inner ring (SVD, SCP: P = 0.005 and DCP: P = 0.042 and PD, SCP: P = 0.003) and outer ring (SVD, SCP: P = 0.007 and DCP: P = 0.030 and PD, SCP: P = 0.020 and DCP: P = 0.025). No significant differences were observed at baseline between DRSS levels 43 and 47. In SD-OCTA, the differences were similar but did not reach statistical significance. The total ischemic index showed an increase in association with diabetic retinopathy (DR) severity, but the differences between DRSS levels did not reach statistical significance. The number of microaneurysms also increased significantly with DR severity (P = 0.033). Statistically significant 6-month progression was detected with SS-OCTA in eyes with DRSS levels 47 and 53 but not in DRSS level 43. In eyes with DRSS level 53, 6-month progression was identified using a combination of metrics of capillary nonperfusion and microaneurysm counts.

Conclusions

In a 6-month period, significant microvascular disease progression can be identified in eyes with DRSS levels 47 and 53 by performing OCTA examinations and microaneurysm counting using CFP.

Financial Disclosure(s)

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

目的评估非增生性糖尿病视网膜病变（NPDR）晚期患者视网膜毛细血管灌注在 6 个月后的进展情况。方法对 60 名 2 型糖尿病患者中分别处于糖尿病视网膜病变严重程度量表（DRSS）43、47 和 53 级的 60 只眼睛进行为期 2 年的前瞻性纵向研究。方法通过 Optos California (Optos plc) 超宽场眼底荧光素血管造影术 (UWF-FFA)、扫描源 OCT 血管造影术 (SS-OCTA) (PLEX Elite 9000, 蔡司) 和光谱域 OCTA (SD-OCTA) (CIRRUS HD-OCT 5000 Angioplex, 蔡司) 对眼睛进行评估。主要结果测量缺血指数由 Optos 获得。通过 OCTA 获取浅层和深层毛细血管丛（SCP 和 DCP）的血管量化指标，即眼窝无血管区、骨骼化血管密度（SVD）和灌注密度（PD）指标。根据 CFP 图像，使用 RetmarkerDR（Retmarker SA，Meteda Group）自动进行微动脉瘤评估。结果扫源 OCTA 指标显示，NPDR 晚期之间存在显著的统计学差异。在内环（SVD、SCP：P = 0.005 和 DCP：P = 0.042；PD、SCP：P = 0.003）和外环（SVD、SCP：P = 0.007 和 DCP：P = 0.030；PD、SCP：P = 0.020 和 DCP：P = 0.025）基线时，发现 DRSS 47 级和 53 级之间存在差异。DRSS 43 级和 47 级在基线时未观察到明显差异。在 SD-OCTA 中，差异类似，但未达到统计学意义。总缺血指数随糖尿病视网膜病变（DR）严重程度的增加而增加，但 DRSS 级别之间的差异未达到统计学意义。微动脉瘤数量也随 DR 严重程度的增加而显著增加（P = 0.033）。在 DRSS 47 级和 53 级的眼球中，SS-OCTA 检测到 6 个月的病情进展具有统计学意义，但在 DRSS 43 级的眼球中没有发现。结论在 6 个月的时间内，通过进行 OCTA 检查和使用 CFP 进行微动脉瘤计数，可以发现 DRSS 等级为 47 和 53 的眼球存在明显的微血管疾病进展。

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引用次数: 0

Automated Detection of Central Retinal Artery Occlusion Using OCT Imaging via Explainable Deep Learning 通过可解释深度学习使用 OCT 成像自动检测视网膜中央动脉闭塞

IF 3.2 Q1 OPHTHALMOLOGY

Ophthalmology science

Pub Date : 2024-10-16 DOI: 10.1016/j.xops.2024.100630

Ansgar Beuse , Daniel Alexander Wenzel MD , Martin Stephan Spitzer MD , Karl Ulrich Bartz-Schmidt MD , Maximilian Schultheiss MD , Sven Poli MD , Carsten Grohmann PhD, MD

Objective

To demonstrate the capability of a deep learning model to detect central retinal artery occlusion (CRAO), a retinal pathology with significant clinical urgency, using OCT data.

Design

Retrospective, external validation study analyzing OCT and clinical baseline data of 2 institutions via deep learning classification analysis.

Subjects

Patients presenting to the University Medical Center Tübingen and the University Medical Center Hamburg-Eppendorf in Germany.

Methods

OCT data of patients suffering from CRAO, differential diagnosis with (sub) acute visual loss (central retinal vein occlusion, diabetic macular edema, nonarteritic ischemic optic neuropathy), and from controls were expertly graded and distinguished into 3 groups. Our methodological approach involved a nested multiclass five fold cross-validation classification scheme.

Main Outcome Measures

Area under the curve (AUC).

Results

The optimal performance of our algorithm was observed using 30 epochs, complemented by an early stopping mechanism to prevent overfitting. Our model followed a multiclass approach, distinguishing among the 3 different classes: control, CRAO, and differential diagnoses. The evaluation was conducted by the “one vs. all” area under the receiver operating characteristics curve (AUC) method. The results demonstrated AUC of 0.96 (95% confidence interval [CI], ± 0.01); 0.99 (95% CI, ± 0.00); and 0.90 (95% CI, ± 0.03) for each class, respectively.

Conclusions

Our machine learning algorithm (MLA) exhibited a high AUC, as well as sensitivity and specificity in detecting CRAO and the differential classes, respectively. These findings underscore the potential for deploying MLAs in the identification of less common etiologies within an acute emergency clinical setting.

Financial Disclosure(s)

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

目的利用 OCT 数据证明深度学习模型检测视网膜中央动脉闭塞（CRAO）的能力，CRAO 是一种临床急需的视网膜病变。方法通过深度学习分类分析，对两家机构的 OCT 和临床基线数据进行回顾性外部验证研究。研究对象在德国图宾根大学医学中心和汉堡-埃彭多夫大学医学中心就诊的患者。方法对CRAO患者、伴有（亚）急性视力丧失（视网膜中央静脉闭塞、糖尿病性黄斑水肿、非动脉缺血性视神经病变）的鉴别诊断患者以及对照组的OCT数据进行专家分级，并将其分为3组。主要结果测量曲线下面积（AUC）。结果我们的算法在使用 30 个历元时达到最佳性能，并辅以早期停止机制以防止过度拟合。我们的模型采用了多类方法，区分了 3 个不同的类别：对照、CRAO 和鉴别诊断。评估采用了 "一个与所有 "接收者操作特征曲线下面积（AUC）法。结果显示，每个类别的 AUC 分别为 0.96（95% 置信区间 [CI]，± 0.01）、0.99（95% CI，± 0.00）和 0.90（95% CI，± 0.03）。这些发现强调了在急诊临床环境中使用 MLA 识别不常见病因的潜力。

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引用次数: 0

The Optical Nature of Myopic Changes in Retinal Vessel Caliber 视网膜血管口径近视变化的光学性质

IF 3.2 Q1 OPHTHALMOLOGY

Ophthalmology science

Pub Date : 2024-10-10 DOI: 10.1016/j.xops.2024.100631

Fabian Yii BSc , Niall Strang MCOptom, PhD , Colin Moulson BSc, MCOptom , Baljean Dhillon FRCPS, FRCOphth , Miguel O. Bernabeu PhD , Tom MacGillivray PhD

<div><h3>Purpose</h3><div>Dimensional measures of retinal features are subject to the optical influence of ocular magnification. We examined the impact of ocular magnification on the association between axial length (AL) and measurements of retinal vessel caliber in fundus photographs.</div></div><div><h3>Design</h3><div>Cross-sectional study.</div></div><div><h3>Participants</h3><div>Eighty-two normal right eyes from healthy participants aged 16 to 31 years.</div></div><div><h3>Methods</h3><div>Central retinal arteriolar and venular equivalents (CRAE and CRVE) were derived from color fundus photographs using semiautomated software. Ordinary least squares linear regression was used to assess the influence of AL (independent variable) on CRAE and CRVE, controlling for age, sex, and ethnicity, both before and after magnification correction using different formulae. These formulae estimate magnification based on different ocular parameters: AL only (Bennnett’s formula), refractive error only (Bengtsson’s formula), and refractive error combined with keratometry (Littmann’s formula). Previous research has primarily relied on Bengtsson’s formula, which is less accurate than Bennett’s formula. We also examined the impact of treating the nontelecentric fundus camera used in this study as telecentric when applying these magnification correction formulae.</div></div><div><h3>Main Outcome Measures</h3><div>Central retinal arteriolar and venular equivalents (in pixels).</div></div><div><h3>Results</h3><div>Before magnification correction, increasing AL was associated with decreasing CRAE (β: −0.49, 95% confidence intervals: −0.89 to −0.09, <em>P</em> = 0.02) and CRVE (β: −0.91, 95% confidence intervals: −1.62 to −0.20, <em>P</em> = 0.01). After magnification correction, this observation was no longer evident, regardless of the correction formula applied. When inappropriately assuming the fundus camera to be telecentric, we observed a bias toward increasing magnification-corrected CRAE and CRVE with increasing AL (β coefficients were positive or became more positive), reaching statistical significance (<em>P</em> < 0.05) for CRAE corrected using Bennett’s or Littmann’s formula, and for CRVE corrected using Bennett’s formula.</div></div><div><h3>Conclusions</h3><div>Failing to correct for ocular magnification results in apparent narrowing of vessels in longer eyes, while inappropriate assumptions about telecentricity during magnification correction introduce an optical artifact that causes apparent widening of vessels. These findings suggest that myopic changes in retinal vessel caliber are optical (not biological) in nature. Proper correction of this effect to accurately derive dimensional measures is a crucial—yet often overlooked—methodological consideration in “oculomics” research investigating retinal biomarkers of systemic conditions.</div></div><div><h3>Financial Disclosure(s)</h3><div>Proprietary or commercial disclosure may be found in the Footnote

目的视网膜特征的尺寸测量受眼球放大倍数的光学影响。我们研究了眼球放大倍数对轴向长度（AL）和眼底照片中视网膜血管口径测量值之间关联的影响。方法使用半自动软件从彩色眼底照片中得出视网膜中央动脉和静脉等值（CRAE 和 CRVE）。使用普通最小二乘法线性回归评估 AL（自变量）对 CRAE 和 CRVE 的影响，同时控制年龄、性别和种族，并在使用不同公式进行放大校正之前和之后进行校正。这些公式根据不同的眼参数估算放大倍数：仅 AL（Bennnett 公式）、仅屈光不正（Bengtsson 公式）和屈光不正与角膜测量相结合（Littmann 公式）。以往的研究主要依赖 Bengtsson 公式，但其准确性不如 Bennett 公式。结果在放大校正前，AL 的增加与 CRAE（β：-0.49，95% 置信区间：-0.89 至 -0.09，P = 0.02）和 CRVE（β：-0.91，95% 置信区间：-1.62 至 -0.20，P = 0.01）的减少相关。放大校正后，无论采用何种校正公式，这一观察结果都不再明显。当不适当地假设眼底照相机为远心时，我们观察到随着 AL 的增加，放大校正后的 CRAE 和 CRVE 有所增加（β 系数为正或变得更正），使用 Bennett 或 Littmann 公式校正的 CRAE 和使用 Bennett 公式校正的 CRVE 达到了统计学意义（P < 0.05）。结论未对眼球放大率进行校正会导致长眼血管明显变窄，而在放大率校正过程中对远心的不恰当假设则会引入光学假象，导致血管明显变宽。这些发现表明，近视眼视网膜血管口径的变化本质上是光学的（而非生物的）。在研究全身性疾病的视网膜生物标志物的 "眼科组学 "研究中，适当纠正这种效应以准确得出尺寸测量值是一个至关重要但却经常被忽视的方法学考虑因素。

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引用次数: 0

ReCLAIM-2: A Randomized Phase II Clinical Trial Evaluating Elamipretide in Age-related Macular Degeneration, Geographic Atrophy Growth, Visual Function, and Ellipsoid Zone Preservation ReCLAIM-2：一项随机 II 期临床试验，评估艾拉格雷在老年性黄斑变性、地理萎缩生长、视觉功能和椭球带保留方面的作用

IF 3.2 Q1 OPHTHALMOLOGY

Ophthalmology science

Pub Date : 2024-10-09 DOI: 10.1016/j.xops.2024.100628

Justis P. Ehlers MD , Allen Hu MD , David Boyer MD , Scott W. Cousins MD , Nadia K. Waheed MD , Philip J. Rosenfeld MD, PhD , David Brown MD , Peter K. Kaiser MD , Anthony Abbruscato PharmD , Gui Gao PhD , Jeffrey Heier MD

Objective

This study evaluated the safety and efficacy of elamipretide in dry age-related macular degeneration (AMD) with noncentral geographic atrophy (GA).

Design

ReCLAIM-2 was a prospective, phase II, randomized, placebo-controlled, double-masked, multicenter trial (NCT03891875).

Subjects

Patients aged ≥55 years with ≥1 eye with dry AMD with GA were enrolled.

Methods

Administration of daily subcutaneous elamipretide 40 mg was investigated in subjects for 48 weeks followed by a 4-week follow-up period.

Main Outcome Measures

The primary efficacy end points were the mean change from baseline (BL) in low-luminance best-corrected visual acuity (LL BCVA) and the change in square root (Sqrt) converted GA area from BL as measured by OCT. Additional predefined end points included ellipsoid zone (EZ) integrity preservation assessment and categorical changes in LL BCVA. The primary safety end point was the incidence and severity of adverse events.

Results

Of the 176 patients randomized, there were 117 and 59 patients in the elamipretide and placebo groups, respectively. Although elamipretide did not meet statistical significance for the primary end points (mean change in LL BCVA and mean change in Sqrt converted GA area), elamipretide produced a 43% reduction in the mean progression from BL in the macular percentage of total EZ attenuation/loss (i.e., complete loss of EZ band; nominal P = 0.0034) and 47% reduction in the mean progression of macular percentage of partial EZ attenuation/degradation (i.e., EZ-retinal pigment endothelium thickness of ≤20 microns; nominal P = 0.0040) versus placebo at week 48. Elamipretide treatment was also associated with significantly more patients experiencing a ≥10 letter gain in LL BCVA versus placebo (14.6% vs. 2.1%; nominal P = 0.0404). Adverse events were reported in 86% of those receiving elamipretide and 71% of the placebo group with the most common events being injection site reactions (e.g., pruritus, injection site pain, bruising, and erythema).

Conclusions

While the primary end points were not met in this phase II study, elamipretide treatment was associated with a slowing of progressive EZ degradation/loss, a surrogate for photoreceptor damage. These findings have important clinical relevance since EZ attenuation/photoreceptor loss precedes and predicts the progressive pathological changes associated with vision loss and AMD. The EZ attenuation/loss end point will serve as the regulatory approved primary end point in the elamipretide phase III clinical development program.

Financial Disclosure(s)

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

研究对象年龄≥55岁且有≥1只眼睛患有干性AMD并伴有GA的患者。方法每天皮下注射艾拉莫雷特40毫克，持续48周，然后进行4周随访。主要结果测量主要疗效终点是低照度最佳校正视力（LL BCVA）与基线（BL）相比的平均变化，以及OCT测量的GA面积与基线相比的平方根（Sqrt）转换变化。其他预定义终点包括椭圆体区 (EZ) 完整性保存评估和 LL BCVA 的分类变化。主要的安全性终点是不良事件的发生率和严重程度。结果在随机抽取的176名患者中，艾拉米雷特组和安慰剂组分别有117名和59名患者。虽然艾拉莫雷特在主要终点（LL BCVA 平均变化和 Sqrt 转换 GA 面积平均变化）上未达到统计学意义，但艾拉莫雷特使黄斑总 EZ 衰减/损失百分比从 BL 开始的平均进展减少了 43%（即 EZ 带完全损失；名义 P=0.05）、第 48 周时，与安慰剂相比，黄斑部分 EZ 衰减/退化（即 EZ-视网膜色素内皮厚度≤20 微米；标称 P = 0.0040）的平均进展减少了 47%。与安慰剂相比，更多患者的LL BCVA增加了≥10个字母（14.6%对2.1%；标称P = 0.0404）。接受艾拉米雷特治疗的患者中有86%出现了不良反应，而安慰剂组中有71%出现了不良反应，其中最常见的不良反应是注射部位反应（如瘙痒、注射部位疼痛、瘀伤和红斑）。结论虽然这项II期研究没有达到主要终点，但艾拉米雷特治疗与减缓EZ的进行性降解/丧失有关，EZ是光感受器损伤的替代物。这些发现具有重要的临床意义，因为EZ衰减/光感受器损失先于并预示着与视力下降和老年性黄斑变性相关的渐进性病理变化。EZ衰减/损失终点将作为艾拉米雷肽III期临床开发计划中经监管部门批准的主要终点。

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引用次数: 0

Interplay between Lipids and Complement Proteins—How Multiomics Data Integration Can Help Unravel Age-related Macular Degeneration Pathophysiology: A Proof-of-concept Study 脂质与补体蛋白之间的相互作用--多组学数据整合如何帮助揭示老年性黄斑变性的病理生理学：概念验证研究

IF 3.2 Q1 OPHTHALMOLOGY

Ophthalmology science

Pub Date : 2024-10-01 DOI: 10.1016/j.xops.2024.100629

Simon Nusinovici PhD , Lei Zhou PhD , Lavanya Raghavan MD , Yih Chung Tham PhD , Hengtong Li MS , Danny Cheung MD , Xiaomeng Wang PhD , Chui Ming Gemmy Cheung MD, PhD , Tien Yin Wong MD, PhD , Usha Chakravarthy MD, PhD , Ching-Yu Cheng MD, PhD

Objective

Our objectives were to identify correlation patterns between complement and lipid pathways using a multiomics data integration approach and to determine how these interconnections affect age-related macular degeneration (AMD).

Design

Nested case-control study.

Subjects and Controls

The analyses were performed in a subset of the Singapore Indian Eye Study. We randomly selected 155 AMD cases and age- and sex-matched them with 155 controls.

Methods

Firstly, a multiomics data integration method was used to identify correlation patterns between the omics data. Then, we tested possible interactions between the lipids and complement proteins using logistic regression models.

Main Outcome Measures

Age-related macular degeneration was determined according to the Beckman classification system. We measured in serum samples 35 complement proteins and 66 lipids, and used 9 genetic variants.

Results

Among the 155 AMD cases, 93 (60.0%) had early and 62 (40.0%) intermediate AMD. Firstly, we identified 2 clusters between complement proteins and lipids involving (1) mannan-binding lectin serine protease 1 and several different high-density lipoprotein particles, and (2) complement factor H-related protein 1, carboxypeptidase N subunit 2 and complement component C8 gamma chain, and sphingomyelin and different cholesterol. Secondly, we identified 1 interaction between complement protein 1R and sphingomyelin with an odds of AMD 2 times higher for individuals with low levels of sphingomyelin and complement protein 1R (odds ratio = 2.13 [1.09, 4.17]).

Conclusions

We report here, using a cutting-edge multiomics integration approach, the complex interconnections between genetic, metabolomics, and proteomic data. This method permitted us to obtain a holistic picture and identify multiomics signature of AMD pathophysiology. These results advocate for a personalized therapeutic approach that accounts for multiple pathways. However, these results need to be validated in larger studies with different ethnic groups.

Financial Disclosure(s)

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

目标我们的目标是利用多组学数据整合方法确定补体和脂质通路之间的相关模式，并确定这些相互联系如何影响年龄相关性黄斑变性（AMD）。我们随机选取了 155 例 AMD 病例，并将其与 155 例对照组进行了年龄和性别匹配。主要结果测量根据贝克曼分类系统确定年龄相关性黄斑变性。我们测量了血清样本中的 35 种补体蛋白和 66 种脂质，并使用了 9 种遗传变异。结果在 155 例 AMD 病例中，93 例（60.0%）为早期 AMD，62 例（40.0%）为中期 AMD。首先，我们在补体蛋白和脂质之间发现了2个群集，涉及（1）甘露结合凝集素丝氨酸蛋白酶1和几种不同的高密度脂蛋白颗粒，以及（2）补体因子H相关蛋白1、羧肽酶N亚基2和补体成分C8γ链，以及鞘磷脂和不同的胆固醇。其次，我们在补体蛋白 1R 和鞘磷脂之间发现了一种相互作用，鞘磷脂和补体蛋白 1R 含量低的个体患老年痴呆症的几率要高出 2 倍（几率比 = 2.13 [1.09, 4.17]）。通过这种方法，我们获得了一个整体图像，并确定了 AMD 病理生理学的多组学特征。这些结果为考虑多种途径的个性化治疗方法提供了依据。然而，这些结果还需要在不同种族群体的大型研究中得到验证。

{"title":"Interplay between Lipids and Complement Proteins—How Multiomics Data Integration Can Help Unravel Age-related Macular Degeneration Pathophysiology: A Proof-of-concept Study","authors":"Simon Nusinovici PhD , Lei Zhou PhD , Lavanya Raghavan MD , Yih Chung Tham PhD , Hengtong Li MS , Danny Cheung MD , Xiaomeng Wang PhD , Chui Ming Gemmy Cheung MD, PhD , Tien Yin Wong MD, PhD , Usha Chakravarthy MD, PhD , Ching-Yu Cheng MD, PhD","doi":"10.1016/j.xops.2024.100629","DOIUrl":"10.1016/j.xops.2024.100629","url":null,"abstract":"<div><h3>Objective</h3><div>Our objectives were to identify correlation patterns between complement and lipid pathways using a multiomics data integration approach and to determine how these interconnections affect age-related macular degeneration (AMD).</div></div><div><h3>Design</h3><div>Nested case-control study.</div></div><div><h3>Subjects and Controls</h3><div>The analyses were performed in a subset of the Singapore Indian Eye Study. We randomly selected 155 AMD cases and age- and sex-matched them with 155 controls.</div></div><div><h3>Methods</h3><div>Firstly, a multiomics data integration method was used to identify correlation patterns between the omics data. Then, we tested possible interactions between the lipids and complement proteins using logistic regression models.</div></div><div><h3>Main Outcome Measures</h3><div>Age-related macular degeneration was determined according to the Beckman classification system. We measured in serum samples 35 complement proteins and 66 lipids, and used 9 genetic variants.</div></div><div><h3>Results</h3><div>Among the 155 AMD cases, 93 (60.0%) had early and 62 (40.0%) intermediate AMD. Firstly, we identified 2 clusters between complement proteins and lipids involving (1) mannan-binding lectin serine protease 1 and several different high-density lipoprotein particles, and (2) complement factor H-related protein 1, carboxypeptidase N subunit 2 and complement component C8 gamma chain, and sphingomyelin and different cholesterol. Secondly, we identified 1 interaction between complement protein 1R and sphingomyelin with an odds of AMD 2 times higher for individuals with low levels of sphingomyelin and complement protein 1R (odds ratio = 2.13 [1.09, 4.17]).</div></div><div><h3>Conclusions</h3><div>We report here, using a cutting-edge multiomics integration approach, the complex interconnections between genetic, metabolomics, and proteomic data. This method permitted us to obtain a holistic picture and identify multiomics signature of AMD pathophysiology. These results advocate for a personalized therapeutic approach that accounts for multiple pathways. However, these results need to be validated in larger studies with different ethnic groups.</div></div><div><h3>Financial Disclosure(s)</h3><div>Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.</div></div>","PeriodicalId":74363,"journal":{"name":"Ophthalmology science","volume":"5 1","pages":"Article 100629"},"PeriodicalIF":3.2,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142655031","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

Systemic Treatment with the Janus Kinase Inhibitor Baricitinib in Ocular Chronic Graft-versus-Host Disease 用 Janus 激酶抑制剂 Baricitinib 对眼部慢性移植物抗宿主病进行全身治疗

IF 3.2 Q1 OPHTHALMOLOGY

Ophthalmology science

Pub Date : 2024-09-30 DOI: 10.1016/j.xops.2024.100627

Taylor McManus BS, MS , Noa G. Holtzman MD , Aaron Zhao BS , Chantal Cousineau-Krieger MD , Susan Vitale PhD, MHS , Edmond J. FitzGibbon MD , Debbie Payne BS, MBA , Janine Newgen COT , Celestina Igbinosun BSN, RN , Annie P. Im MD , Cody Peer MS, PhD , William Douglas Figg Sr. Pharm D , Edward W. Cowen MD , Jacqueline W. Mays DDS, PhD , Steven Pavletic MD, PhD , M.Teresa Magone MD

Objective

To investigate the effects of oral baricitinib on ocular surface disease (OSD) in patients with chronic graft-versus-host disease (cGVHD).

Design

Prospective phase 1 to 2 single institution trial.

Subjects

Eighteen patients with ocular graft-versus-host-disease (oGVHD) and systemic steroid-refractory cGVHD.

Methods

Oral baricitinib (2 mg and 4 mg) was administered daily for up to 12 months in an intrapatient dose-escalation design. National Institutes of Health (NIH) oGVHD score, vision, corneal Oxford staining (COS), tear break-up time (TBUT), Schirmer I test (ST) without anesthesia, and microliter tear equivalent conversion were assessed at baseline, 6 months (primary efficacy end point), and 12 months if patients remained on the drug.

Main Outcome Measures

Improvement in NIH oGVHD score, COS, TBUT, and ST results in patients with and without conjunctival fibrosis at 6 months.

Results

At 6 months, the NIH oGVHD score significantly improved (P = 0.014) with all OSD parameters also showing improvement, though not statistically significant. COS baseline, 2.17 to 0.95; TBUT baseline, 6.66 to 8.18 seconds, Schirmer I baseline, 3.86 mm (2.6 μl) to 5.56 mm (3.9 μl). For patients continuing treatment at 12 months improvements persisted compared with the baseline but remained statistically nonsignificant. Corneal Oxford staining decreased to 0.94; TBUT increased to 8.95 seconds, and ST improved to 10.19 mm (7.2 μL). Conjunctival fibrosis was present in 39% (n = 7) of the patients at baseline. The greatest improvement was observed in the 11 patients without prior conjunctival fibrosis compared with the baseline: COS 1.84, TBUT 6.32 seconds, ST 4.07 mm (2.1 μl); 6 months: COS 0.25 (P = 0.018), TBUT 8.62 seconds, ST 9.12 mm (5.4 μl); 12 months: COS 0, TBUT 10.29 seconds, ST 16.88 mm (10.6 μl). Vision was stable in all groups. Two patients developed asymptomatic, self-limited conjunctival papillomas, and 1 patient developed uncomplicated bacterial conjunctivitis twice. No dose limiting toxicity was observed. Severe adverse events with hospitalizations for possible drug-related systemic infections occurred in 5 patients.

Conclusions

Systemic baricitinib was well-tolerated, improved NIH oGVHD scores and OSD parameters in patients with oGVHD, with the greatest benefits observed in patients without pre-existing conjunctival fibrosis. Conjunctival fibrosis may affect outcomes and should be considered in patient selection for clinical trials.

Financial Disclosure(s)

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

目的研究口服巴利昔尼对慢性移植物抗宿主病（cGVHD）患者眼表疾病（OSD）的影响。方法采用患者内剂量递增设计，每天口服巴利昔尼（2 毫克和 4 毫克）长达 12 个月。美国国立卫生研究院（NIH）oGVHD评分、视力、角膜牛津染色（COS）、泪液破裂时间（TBUT）、无麻醉施尔默I试验（ST）和微升泪液当量转换分别在基线、6个月（主要疗效终点）和12个月时进行评估（如果患者继续用药）。结果6个月时，NIH oGVHD评分显著改善（P = 0.014），所有OSD参数也有所改善，但无统计学意义。COS基线从2.17秒降至0.95秒；TBUT基线从6.66秒降至8.18秒；Schirmer I基线从3.86毫米（2.6微升）升至5.56毫米（3.9微升）。与基线相比，继续治疗 12 个月的患者病情仍有改善，但在统计学上仍无显著性。角膜牛津染色降至 0.94；TBUT 增至 8.95 秒，ST 增至 10.19 毫米（7.2 μL）。基线时，39% 的患者（n = 7）出现结膜纤维化。与基线值相比，11 名没有结膜纤维化的患者的病情改善最大：COS 1.84，TBUT 6.32 秒，ST 4.07 毫米（2.1 μl）；6 个月：与基线相比：COS 1.84，TBUT 6.32 秒，ST 4.07 毫米（2.1 微升）；6 个月：COS 0.25（P = 0.018），TBUT 8.62 秒，ST 9.12 毫米（5.4 微升）；12 个月：12 个月：COS 0，TBUT 10.29 秒，ST 16.88 毫米（10.6 μl）。各组患者的视力均保持稳定。两名患者出现了无症状的自限性结膜乳头状瘤，一名患者出现了两次无并发症的细菌性结膜炎。没有观察到限制剂量的毒性。结论系统性巴利昔尼耐受性良好，可改善oGVHD患者的NIH oGVHD评分和OSD参数，无结膜纤维化的患者获益最大。结膜纤维化可能会影响治疗效果，在选择患者进行临床试验时应加以考虑。

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引用次数: 0