Ophthalmology science最新文献

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。

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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。

{"title":"Systemic Treatment with the Janus Kinase Inhibitor Baricitinib in Ocular Chronic Graft-versus-Host Disease","authors":"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","doi":"10.1016/j.xops.2024.100627","DOIUrl":"10.1016/j.xops.2024.100627","url":null,"abstract":"<div><h3>Objective</h3><div>To investigate the effects of oral baricitinib on ocular surface disease (OSD) in patients with chronic graft-versus-host disease (cGVHD).</div></div><div><h3>Design</h3><div>Prospective phase 1 to 2 single institution trial.</div></div><div><h3>Subjects</h3><div>Eighteen patients with ocular graft-versus-host-disease (oGVHD) and systemic steroid-refractory cGVHD.</div></div><div><h3>Methods</h3><div>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.</div></div><div><h3>Main Outcome Measures</h3><div>Improvement in NIH oGVHD score, COS, TBUT, and ST results in patients with and without conjunctival fibrosis at 6 months.</div></div><div><h3>Results</h3><div>At 6 months, the NIH oGVHD score significantly improved (<em>P</em> = 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 (<em>P</em> = 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.</div></div><div><h3>Conclusions</h3><div>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.</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 100627"},"PeriodicalIF":3.2,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142655032","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

Intraretinal Retinal Pigment Epithelium Cells in Age-Related Macular Degeneration 老年性黄斑变性中的视网膜内视网膜色素上皮细胞

IF 3.2 Q1 OPHTHALMOLOGY

Ophthalmology science

Pub Date : 2024-09-30 DOI: 10.1016/j.xops.2024.100626

Songhomitra Panda-Jonas MD , Rahul A. Jonas MD , Jie Xu MD , Ya Xing Wang MD , Jost B. Jonas MD

Purpose

To examine intraretinally migrated retinal pigment epithelium cells (iRPECs) in enucleated human eyes with various retinal conditions and corresponding intraretinal hyperreflective bodies (iHRBs) in a large cohort of patients with age-related macular degeneration (AMD) in China.

Design

Population-based study and histomorphometric investigation.

Participants

Participants of the population-based Beijing Eye Study and enucleated human eyes.

Methods

OCT-based and fundus photography-based examination of the macula of the Beijing Eye Study participants and light-microscopical histomorphometry of enucleated human eyes.

Main Outcome Measures

Presence and location of iRPECs and iHRBs.

Results

In the Beijing Eye Study (6551 eyes; 3301 participants), the prevalence of intermediate AMD and late AMD was 331 (5.1%) and 44 (0.6%), respectively. All 42 eyes with intermediate AMD and macular hyperpigmentation had iHRBs at locations corresponding spatially with macular hyperpigmentation on the fundus photographs. Among all eyes with intermediate AMD (n = 331), iHRBs were detected in 262 (79.2%) eyes. The most internal location of the iHRBs was at the ellipsoid zone in 46 (13.9%) eyes, at the external limiting membrane (ELM) in 45 (13.6%) eyes, and in the outer nuclear layer in 145 (43.8%) eyes. Out of the 262 eyes with iHRBs, 186 (71.0%) eyes showed a corresponding defect in the ellipsoid zone, and 128 (48.9%) eyes showed a defect in the ELM. The eyes with an iHRB located beneath the ELM did not show an ELM defect. The iHRBs were associated with a plume-like appearance and with a smoke-like appearance in 20 (7.6%) eyes and 137 (52.3%) eyes, respectively. All iHRBs did not have a shadow on the OCT images. Similar findings were obtained in the eyes with late AMD. Among 237 eyes examined histologically, 21 globes showed iRPECs: 8 eyes in parapapillary α zone/β zone; 5 eyes with myopic patchy atrophies, and 3 eyes with AMD. The iRPECs were spatially associated with an ELM defect and were not surrounded by a basal membrane.

Conclusions

Intraretinal hyperreflective bodies can be found in 3 out of 4 eyes with intermediate AMD, correlate histologically with intraretinally located (migrated) retinal pigment epithelium cells, and correspond spatially with localized defects of the ellipsoid zone and ELM.

Financial Disclosure(s)

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

目的研究中国一大批年龄相关性黄斑变性（AMD）患者的去核人眼中视网膜内移行的视网膜色素上皮细胞（irpecs）以及相应的视网膜内高反射体（iHRBs）。主要结果测量iRPECs和iHRBs的存在和位置。结果在北京眼科研究（6551只眼睛；3301名参与者）中，中期AMD和晚期AMD的患病率分别为331（5.1%）和44（0.6%）。所有 42 只患有中期 AMD 和黄斑色素沉着的眼睛都在眼底照片上与黄斑色素沉着相对应的位置出现了 iHRB。在所有患有中度 AMD 的眼睛（n = 331）中，有 262 只眼睛（79.2%）检测到了 iHRB。46只（13.9%）眼的iHRB位于椭圆形区，45只（13.6%）眼的iHRB位于外缘膜（ELM），145只（43.8%）眼的iHRB位于核外层。在 262 只出现 iHRB 的眼睛中，186 只（71.0%）眼睛的椭圆形区出现了相应的缺损，128 只（48.9%）眼睛的 ELM 出现了缺损。iHRB位于ELM下方的眼球未显示ELM缺损。分别有 20 只（7.6%）眼睛和 137 只（52.3%）眼睛的 iHRB 与羽状外观和烟雾状外观有关。所有 iHRB 在 OCT 图像上都没有阴影。晚期 AMD 患者也有类似的发现。在接受组织学检查的237只眼球中，有21只眼球出现了iRPECs：8只眼球位于毛旁α区/β区；5只眼球患有近视斑片状萎缩；3只眼球患有AMD。iRPECs在空间上与ELM缺损相关，周围没有基底膜。结论在4只患有中度AMD的眼睛中，有3只眼睛可以发现视网膜超反射体，在组织学上与视网膜内定位（移行）的视网膜色素上皮细胞相关，在空间上与椭圆形区和ELM的局部缺损相对应。

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引用次数: 0

Relationship of Inflammatory Mediators (Interleukin and Cortisol Concentrations) with Corneal Epithelial Quantifiable Metrics 炎症介质（白细胞介素和皮质醇浓度）与角膜上皮量化指标的关系

IF 3.2 Q1 OPHTHALMOLOGY

Ophthalmology science

Pub Date : 2024-09-19 DOI: 10.1016/j.xops.2024.100624

Marcony R. Santhiago MD, PhD , Larissa R. Stival MD, PhD , Daniella C. Araujo PhD , Rosalia Antunes-Foschini MD, PhD , Marcia C. Toledo MD , Ianne L.S. Nunes MS , Claudia R. Morgado MD , Newton Kara-Junior MD, PhD

<div><h3>Purpose</h3><div>To investigate the relationship of inflammatory biomarkers with corneal epithelial quantifiable metrics in patients with keratoconus and in healthy eyes.</div></div><div><h3>Design</h3><div>Prospective observational comparative study.</div></div><div><h3>Participants</h3><div>This study included 100 eyes of 100 patients: 48 eyes of 48 patients with keratoconus and 52 healthy eyes of 52 healthy controls.</div></div><div><h3>Methods</h3><div>The concentrations of tear cytokines were investigated in both groups: interleukin (IL) 1B, IL6, IL8, IL10, IL12p70, and tumor necrosis factor α (TNFα) were obtained by capillary flow and measured using flow cytometer. Cortisol concentrations were determined in both groups from the most proximal hair segment as an index of cumulative secretion and measured by liquid chromatography mass spectrometry. Epithelial variables were obtained with OCT. Pearson correlation (r) was used to measure linear dependence between 2 different variables.</div></div><div><h3>Main Outcome Measures</h3><div>Investigating the existence, strength, and significance of any correlation between inflammatory biomarkers (IL1B, IL6, IL8, IL10, IL12p70, TNFα, and hair cortisol concentration) and OCT corneal epithelial quantifiable variables such as minimum and maximum epithelial thickness of the map, difference between the minimum and maximum (Epithelial Min-Max) and standard deviation of the epithelial thickness of the map (Epithelial Std Dev), and average epithelial thickness of the superior and inferior regions of the map.</div></div><div><h3>Results</h3><div>Eyes with keratoconus presented statistically significantly higher levels of IL1b (<em>P</em> = 0.02), IL6 (<em>P</em> < 0.0001), IL8 (<em>P</em> < 0.0001), and TNFα (<em>P</em> < 0.0001) and hair cortisol concentration (<em>P</em> = 0.01) compared with healthy controls.</div><div>There was a significant correlation between IL6 and measurement Epithelium Min-Max [Pearson = −0.59 (−0.69, −0.47); <em>P</em> < 0.0001] and Epithelial Std Dev (Pearson = +0.56 [0.44, 0.67]; <em>P</em> < 0.0001). There was a significant correlation between hair cortisol concentration and Epithelium Min-Max (Pearson = −0.27 [−0.42, −0.1]; <em>P</em> < 0.0001]) and Epithelium Std Dev groups (Pearson = +0.2 [0.03, 0.36]; <em>P</em> = 0.021). There was also a significant correlation between TNFα and Epithelial Max (Pearson = −0.37 [−0.55, 0.17]; <em>P</em> < 0.0001). We found no significant correlation between the concentration of IL1b, IL8, IL10, and IL2p70 with any epithelium parameters.</div></div><div><h3>Conclusions</h3><div>The higher concentration of inflammatory markers (IL6 and hair cortisol) in eyes with keratoconus present a significant correlation with OCT metrics identifying epithelial variability, such as Epithelial Min-Max and Std Dev. These findings demonstrate the role of chronic inflammation in eyes with keratoconus, and that these epithelial change

目的研究角膜炎患者和健康眼的炎症生物标志物与角膜上皮量化指标的关系：方法对两组患者的泪液细胞因子浓度进行调查：白细胞介素（IL）1B、IL6、IL8、IL10、IL12p70和肿瘤坏死因子α（TNFα）通过毛细管流动获得，并使用流式细胞仪进行测量。通过液相色谱质谱法测定两组毛发的皮质醇浓度，作为累积分泌的指标。上皮变量通过 OCT 获得。皮尔逊相关性（r）用于测量两个不同变量之间的线性关系。主要结果测量调查炎症生物标记物（IL1B、IL6、IL8、IL10、IL12p70、TNFα和毛发皮质醇浓度）与 OCT 角膜上皮量化变量（如地图的最小和最大上皮厚度）之间是否存在相关性、相关性的强度和意义、上皮厚度最小值和最大值之差（Epithelial Min-Max）和上皮厚度标准偏差（Epithelial Std Dev），以及上、下角膜上皮厚度的平均值。结果与健康对照组相比，角膜炎患者的 IL1b (P = 0.02)、IL6 (P < 0.0001)、IL8 (P < 0.0001)、TNFα (P < 0.0001) 和毛发皮质醇浓度（P = 0.与健康对照组相比，IL6与测量上皮最小值-最大值（Pearson = -0.59 (-0.69, -0.47)；P <；0.0001）和上皮标准偏差（Pearson = +0.56 [0.44, 0.67]；P <；0.0001）之间存在显著相关性。）毛发皮质醇浓度与上皮最小值组（Pearson = -0.27 [-0.42, -0.1]；P <；0.0001]）和上皮标准差组（Pearson = +0.2 [0.03, 0.36]；P = 0.021）之间存在明显相关性。TNFα 与上皮最大值之间也存在明显的相关性（Pearson = -0.37 [-0.55, 0.17]；P < 0.0001）。结论角膜炎患者眼部炎症标志物（IL6 和毛发皮质醇）浓度较高，与识别上皮变异性的 OCT 指标（如上皮最小值-最大值和 Std Dev）存在明显相关性。这些研究结果表明了慢性炎症在角膜炎患者眼中的作用，而且用 OCT 检测到的这些上皮变化对这一炎症过程非常敏感。

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引用次数: 0

Finite Element Analysis of Mechanical Ocular Sequelae from Badminton Shuttlecock Projectile Impact 羽毛球毽弹丸冲击眼部机械后遗症的有限元分析

IF 3.2 Q1 OPHTHALMOLOGY

Ophthalmology science

Pub Date : 2024-09-19 DOI: 10.1016/j.xops.2024.100625

John D. Hong PhD , Jose A. Colmenarez MS , Elliot H. Choi MD, PhD , Alex Suh BS , Andrew Suh BS , Matthew Lam MD , Annette Hoskin PhD , Don S. Minckler MD, MS , Ken Y. Lin MD, PhD , Kourosh Shahraki MD , Rupesh Agrawal MD , Pengfei Dong PhD , Linxia Gu PhD , Donny W. Suh MD, MBA

Purpose

With the growing popularity of badminton worldwide, the incidence of badminton-related ocular injuries is expected to rise. The high velocity of shuttlecocks renders ocular traumas particularly devastating, especially with the possibility of permanent vision loss. This study investigated the mechanism behind ocular complications through simulation analyses of mechanical stresses and pressures upon shuttlecock impact.

Design

Computational simulation study.

Participants

None.

Methods

A 3-dimensional human eye model was reconstructed based on the physiological and biomechanical properties of various ocular tissues. Finite element analysis simulations involved a frontal collision with a shuttlecock projectile at 128.7 km/hour (80 mph). Intraocular pressure (IOP) changes and tissue stress were mapped and quantified in the following ocular structures: the limbus, ciliary body, zonular fibers, ora serrata, retina, and optic nerve head.

Main Outcome Measures

Intraocular pressure and tissue stress.

Results

Upon shuttlecock impact, compressive force was transferred to the anterior pole of the cornea, propagating posteriorly to the optic nerve head. Deflection of forces anteriorly contributed to refractory oscillations of compressive and tensile stress of ocular tissue. Initial impact led to a momentary (<1 ms) spike in IOP 5.66 MPa (42.5 × 10³ mmHg) that radially distributed for a very brief instance (<1 ms) of pressure at the trabecular meshwork of the iridocorneal angle of 1.25 MPa (9.4 × 10³ mmHg). The lens had a maximal posterior displacement of 1.5 mm with peak zonular fiber tensile strain of 52%. The limbus, ciliary body, and ora serrata had a peak tensile stress of 5.16 MPa, 1.90 MPa, and 0.62 MPa, respectively. Compressive force from the sclera concentrated at the optic nerve head for a peak stress of 5.97 MPa while peak pressure from vitreous humor was 7.99 MPa.

Conclusions

Shuttlecock impact led to a very brief, substantial rise in pressure and stress significant for tissue damage and subsequent complications, such as secondary glaucoma, angle recession, lens subluxation, hyphema, or retinal dialysis. Our findings offer valuable mechanistic insights into how ocular structures are affected by shuttlecock projectile impact to inform clinical assessments and treatment strategies, while highlighting the importance of protective eyewear in racket sports.

Financial Disclosures

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

目的随着羽毛球运动在世界范围内的日益普及，与羽毛球运动相关的眼部损伤的发生率预计会上升。高速旋转的羽毛球使眼部创伤尤其具有破坏性，特别是有可能造成永久性视力丧失。本研究通过对毽子撞击时的机械应力和压力进行模拟分析，研究眼部并发症背后的机理。有限元分析模拟了以 128.7 公里/小时（80 英里/小时）的速度与毽子弹丸的正面碰撞。主要结果测量眼压和组织应力。结果毽子撞击时，压缩力传递到角膜前极，并向后传播到视神经头。力向前方的偏转导致眼组织的压应力和拉应力发生折返性振荡。最初的撞击导致眼压瞬时（1 毫秒）飙升至 5.66 兆帕（42.5 × 103 毫米汞柱），在虹膜角小梁网的压力为 1.25 兆帕（9.4 × 103 毫米汞柱）的极短时间内（1 毫秒），压力呈放射状分布。晶状体的最大后移量为 1.5 毫米，晶状体纤维拉伸应变的峰值为 52%。角膜缘、睫状体和血清口的拉伸应力峰值分别为 5.16 兆帕、1.90 兆帕和 0.62 兆帕。来自巩膜的压迫力集中在视神经头，峰值应力为 5.97 兆帕，而来自玻璃体的峰值压力为 7.99 兆帕。我们的研究结果为了解毽球弹射物如何影响眼部结构提供了宝贵的机理见解，为临床评估和治疗策略提供了依据，同时强调了在球拍类运动中佩戴防护眼镜的重要性。

{"title":"Finite Element Analysis of Mechanical Ocular Sequelae from Badminton Shuttlecock Projectile Impact","authors":"John D. Hong PhD , Jose A. Colmenarez MS , Elliot H. Choi MD, PhD , Alex Suh BS , Andrew Suh BS , Matthew Lam MD , Annette Hoskin PhD , Don S. Minckler MD, MS , Ken Y. Lin MD, PhD , Kourosh Shahraki MD , Rupesh Agrawal MD , Pengfei Dong PhD , Linxia Gu PhD , Donny W. Suh MD, MBA","doi":"10.1016/j.xops.2024.100625","DOIUrl":"10.1016/j.xops.2024.100625","url":null,"abstract":"<div><h3>Purpose</h3><div>With the growing popularity of badminton worldwide, the incidence of badminton-related ocular injuries is expected to rise. The high velocity of shuttlecocks renders ocular traumas particularly devastating, especially with the possibility of permanent vision loss. This study investigated the mechanism behind ocular complications through simulation analyses of mechanical stresses and pressures upon shuttlecock impact.</div></div><div><h3>Design</h3><div>Computational simulation study.</div></div><div><h3>Participants</h3><div>None.</div></div><div><h3>Methods</h3><div>A 3-dimensional human eye model was reconstructed based on the physiological and biomechanical properties of various ocular tissues. Finite element analysis simulations involved a frontal collision with a shuttlecock projectile at 128.7 km/hour (80 mph). Intraocular pressure (IOP) changes and tissue stress were mapped and quantified in the following ocular structures: the limbus, ciliary body, zonular fibers, ora serrata, retina, and optic nerve head.</div></div><div><h3>Main Outcome Measures</h3><div>Intraocular pressure and tissue stress.</div></div><div><h3>Results</h3><div>Upon shuttlecock impact, compressive force was transferred to the anterior pole of the cornea, propagating posteriorly to the optic nerve head. Deflection of forces anteriorly contributed to refractory oscillations of compressive and tensile stress of ocular tissue. Initial impact led to a momentary (<1 ms) spike in IOP 5.66 MPa (42.5 × 10<sup>3</sup> mmHg) that radially distributed for a very brief instance (<1 ms) of pressure at the trabecular meshwork of the iridocorneal angle of 1.25 MPa (9.4 × 10<sup>3</sup> mmHg). The lens had a maximal posterior displacement of 1.5 mm with peak zonular fiber tensile strain of 52%. The limbus, ciliary body, and ora serrata had a peak tensile stress of 5.16 MPa, 1.90 MPa, and 0.62 MPa, respectively. Compressive force from the sclera concentrated at the optic nerve head for a peak stress of 5.97 MPa while peak pressure from vitreous humor was 7.99 MPa.</div></div><div><h3>Conclusions</h3><div>Shuttlecock impact led to a very brief, substantial rise in pressure and stress significant for tissue damage and subsequent complications, such as secondary glaucoma, angle recession, lens subluxation, hyphema, or retinal dialysis. Our findings offer valuable mechanistic insights into how ocular structures are affected by shuttlecock projectile impact to inform clinical assessments and treatment strategies, while highlighting the importance of protective eyewear in racket sports.</div></div><div><h3>Financial Disclosures</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 100625"},"PeriodicalIF":3.2,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142655115","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

Barriers to Extracting and Harmonizing Glaucoma Testing Data: Gaps, Shortcomings, and the Pursuit of FAIRness 提取和统一青光眼检测数据的障碍：差距、不足和对公平性的追求

IF 3.2 Q1 OPHTHALMOLOGY

Ophthalmology science

Pub Date : 2024-09-14 DOI: 10.1016/j.xops.2024.100621

Niloofar Radgoudarzi BS, Shahin Hallaj MD, Michael V. Boland MD, PhD, Brian Stagg MD, Sophia Y. Wang MD, MS, Benjamin Xu MD, PhD, Swarup S. Swaminathan MD, Eric N. Brown MD, PhD, Aiyin Chen MD, Catherine Q. Sun MD, Dilru C. Amarasekera MD, Jonathan S. Myers MD, Murtaza Saifee MD, William Halfpenny MB BChir, MEng, Keri Dirkes MPH, Linda Zangwill PhD, Kerry E. Goetz PhD, MS, Michelle Hribar PhD, MS, Sally L. Baxter MD, MSc

引用次数: 0

An Eye on Extracellular Vesicles: Trends and Clinical Translations in Vision Research 细胞外囊泡：视觉研究的趋势和临床应用

IF 3.2 Q1 OPHTHALMOLOGY

Ophthalmology science

Pub Date : 2024-09-12 DOI: 10.1016/j.xops.2024.100619

Rahul M. Dhodapkar MD , Eric Jung MD , Sun Young Lee MD, PhD

Purpose

To perform a review of research, funding, and clinical translation efforts for extracellular vesicles (EVs) within vision science.

Design

Retrospective analysis of publication, funding, and clinical trials data.

Methods

A pretrained large language model (Jina2) was used to create semantic embeddings for 41 282 abstracts from articles related to EVs archived on EMBASE and published between January 1966 and January 2024. The articles were projected and clustered according to semantic embedding similarity, and research subdomains for EVs were determined through inspection of term frequency-inverse document frequency weighted word clouds. Mann–Kendall trend analysis was performed to identify current areas of growth within EV research. Additionally, National Institutes of Health funding data from RePORT Expenditures and Results and clinical trials data from ClinicalTrials.gov were analyzed to correlate publication trends with funding support and clinical translation efforts.

Results

Unsupervised clustering and Mann–Kendall trend analysis identified wound healing/regeneration (P = 0.030) and neurodegenerative disease (P = 0.049) as significantly accelerating in growth of publication over time. Ophthalmology-restricted subset analysis identified that publications in age-related macular degeneration (P = 0.191) and clinical applications (P = 0.086) are no longer growing at a significant rate. Analysis of funding data identified that the National Cancer Institute was the top funding institution overall, but that the National Institute on Aging is rapidly advancing in terms of funding EV research and trials. Analysis of ClinicalTrials.gov data highlights a dearth of clinical trials within ophthalmology despite a growing number of studies in other medical subfields.

Conclusions

Extracellular vesicles remain a promising substrate for both the identification and treatment of vision-threatening diseases. A better understanding of the current landscape of research and funding trends should help to inform future funding and translational efforts.

Financial Disclosures

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

目的对视觉科学中细胞外囊泡（EVs）的研究、资助和临床转化工作进行回顾。方法使用预先训练好的大型语言模型（Jina2）为EMBASE归档的、1966年1月至2024年1月期间发表的与EVs相关的41282篇文章摘要创建语义嵌入。根据语义嵌入相似性对文章进行投影和聚类，并通过检查词频-反文档频率加权词云确定 EVs 的研究子域。通过 Mann-Kendall 趋势分析，确定了当前电动汽车研究的增长领域。此外，还分析了来自 RePORT Expenditures and Results 的美国国立卫生研究院资金数据和来自 ClinicalTrials.gov 的临床试验数据，以将论文发表趋势与资金支持和临床转化工作联系起来。结果无监督聚类和 Mann-Kendall 趋势分析发现，随着时间的推移，伤口愈合/再生（P = 0.030）和神经退行性疾病（P = 0.049）的论文发表增长速度明显加快。眼科限制子集分析发现，年龄相关性黄斑变性（P = 0.191）和临床应用（P = 0.086）方面的论文不再显著增长。对资助数据的分析表明，美国国立癌症研究所是总体资助最多的机构，但美国国立老龄化研究所在资助EV研究和试验方面进展迅速。对 ClinicalTrials.gov 数据的分析表明，尽管其他医学子领域的研究数量在不断增加，但眼科领域的临床试验却十分匮乏。更好地了解当前的研究和资助趋势应有助于为未来的资助和转化工作提供信息。财务披露专利或商业披露可参见本文末尾的脚注和披露。

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引用次数: 0

Association of Hyperautofluorescence Signals with Geographic Atrophy Progression in the METformin for the MINimization of Geographic Atrophy Progression Trial 高荧光信号与 METformin-MINimization of Geographic Atrophy Progression 试验中地理萎缩进展的关系

IF 3.2 Q1 OPHTHALMOLOGY

Ophthalmology science

Pub Date : 2024-09-12 DOI: 10.1016/j.xops.2024.100620

Abu Tahir Taha BS , Liangbo Linus Shen MD , Antonio Diaz BS , Noor Chahal BS , Jasmeet Saroya BS , Mengyuan Sun PhD , Michael J. Allingham MD, PhD , Sina Farsiu PhD , Glenn Yiu MD, PhD , Jeremy D. Keenan MD, MPH , Jay M. Stewart MD

Purpose

To investigate the association between rim area focal hyperautofluorescence (RAFH) signals and geographic atrophy (GA) growth rates, as well as the impact of oral metformin on the longitudinal change of RAFH.

Design

Secondary analysis of a randomized controlled trial.

Participants

Seventy-one eyes from 44 participants with GA and ≥6 months of follow-up in the METformin for the MINimization of geographic atrophy progression study.

Methods

Fundus autofluorescence images were captured using a 488 nm excitation wavelength. Two masked graders identified and measured RAFH lesions using proprietary semiautomatic segmentation software and ImageJ. We calculated RAFH by dividing the areas of hyperautofluorescence within a 450-μm rim circumscribing the GA by the total area enclosed within this rim.

Main Outcome Measures

Longitudinal changes in RAFH and GA area.

Results

Baseline RAFH was positively associated with the baseline square root of GA area 0.065/year (P < 0.001). In the entire study cohort, higher baseline RAFH was associated with a faster GA area growth rate in mm²/year (Spearman’s ρ = 0.53; P < 0.001). The association became weaker in square root-transformed GA area growth (ρ = 0.19, P = 0.11) and perimeter-adjusted GA growth rate (ρ = 0.28, P = 0.02), achieving statistical significance only in the latter. When this analysis was stratified into 3 baseline GA tertiles, the first and second tertiles showed weak to moderate association with statistical significance in all 3 modes of GA growth rates. Rim area focal hyperautofluorescence increased slightly but significantly over time at 0.020/year (P < 0.01). Rim area focal hyperautofluorescence increased slightly but significantly over time at 0.020/year (P < 0.01). The use of oral metformin was not significantly associated with the change in RAFH over time compared with the observation group (0.023/year vs. 0.016/year; P = 0.29).

Conclusions

Increased baseline RAFH is associated with faster GA area progression. However, the effect size of this association may depend on the baseline GA lesion size such that small to medium-sized GA lesions display this relationship regardless of the mode of the calculation of GA growth rate.

Financial Disclosures

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

目的研究边缘区局灶性高自荧光（RAFH）信号与地理萎缩（GA）生长率之间的关联，以及口服二甲双胍对RAFH纵向变化的影响。方法使用488 nm激发波长采集Fundus自荧光图像。两名蒙面分级人员使用专有的半自动分割软件和 ImageJ 识别并测量 RAFH 病变。我们计算 RAFH 的方法是，将环绕 GA 的 450 微米边缘内的高荧光区域除以该边缘内的总面积。结果基线 RAFH 与 GA 面积的基线平方根 0.065/年呈正相关（P < 0.001）。在整个研究队列中，基线 RAFH 越高，GA 面积的增长速度越快，单位为 mm2/年（Spearman's ρ = 0.53; P <0.001）。这种关联在经平方根转换的 GA 面积增长率（ρ = 0.19，P = 0.11）和周长调整后的 GA 增长率（ρ = 0.28，P = 0.02）中变得较弱，仅在后者中达到统计学意义。当该分析被分为 3 个基线 GA 三等分时，第一和第二等分显示出弱到中等程度的关联性，在所有 3 种 GA 增长率模式中均有统计学意义。边缘区局灶性高自荧光随着时间的推移略有增加，但显著性为 0.020/年（P < 0.01）。边缘区局灶性高自荧光略有增加，但随着时间的推移显著增加，0.020/年（P <0.01）。与观察组相比，口服二甲双胍与 RAFH 随时间的变化无显著相关性（0.023/年 vs. 0.016/年；P = 0.29）。然而，这种关联的效应大小可能取决于基线GA病变的大小，因此无论GA生长率的计算模式如何，中小型GA病变都会显示出这种关系。

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引用次数: 0

Characterization of the Retinal Phenotype Using Multimodal Imaging in Novel Compound Heterozygote Variants of CYP2U1 利用多模态成像确定 CYP2U1 新型复合杂合子变异体视网膜表型的特征

IF 3.2 Q1 OPHTHALMOLOGY

Ophthalmology science

Pub Date : 2024-09-11 DOI: 10.1016/j.xops.2024.100618

Ferenc B. Sallo MD, PhD , Chantal Dysli MD, PhD , Franz Josef Holzer MD , Emmanuelle Ranza MD , Michel Guipponi MD , Stylianos E. Antonarakis MD , Francis L. Munier MD , Alan C. Bird MD , Daniel F. Schorderet MD , Beatrice Rossillion MD , Veronika Vaclavik MD

Purpose

To report the retinal phenotype in 2 patients simulating type 2 macular telangiectasis with new variants in CYP2U1 implicated in hereditary spastic paraplegia type 56 (HSP 56).

Design

Cross sectional case series study.

Participants

Five members of a non-consanguineous family (parents and 3 male children) were investigated.

Methods

All family members underwent a full ophthalmic evaluation and multimodal retinal imaging. Two family members demonstrating retinal anomalies underwent additional OCT angiography, dual wavelength autofluorescence and fluorescence lifetime imaging ophthalmoscopy, kinetic perimetry, fundus-correlated microperimetry, electroretinography, and electro-oculography. Whole-exome sequencing was performed in all 5 family members.

Main Outcome Measures

To characterize the retinal phenotype in affected patients with variants in CYP2U1, using multimodal imaging: dual-wavelength autofluorescence, fluorescence lifetime, OCT angiography.

Results

The 2 siblings with compound heterozygous novel variants c.452C>T; p.(Pro151Leu), c.943C>T; p.(Gln315Ter) in CYP2U1 demonstrated parafoveal loss of retinal transparency and hyperreflectivity to blue light, redistribution of macular pigment to the parafoveal edge, photoreceptor loss, and fluorescence lifetime imaging ophthalmoscopy anomalies: a pattern compatible with that seen in macular telangiectasia type 2 (MacTel). One had manifest neurological abnormalities since early childhood; the second had no neurological abnormalities. Each parent and the third sibling were heterozygous for 1 variant and were neurologically and ophthalmically normal.

Conclusions

These CYP2U1 variants are associated with a retinal phenotype very similar to that otherwise specific for MacTel, suggestive of possible links in the etiology and pathogenesis of these diseases.

Financial Disclosure(s)

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

目的报告 2 例类似 2 型黄斑毛细血管扩张症的患者的视网膜表型，这些患者体内的 CYP2U1 存在新变异，与遗传性痉挛性截瘫 56 型（HSP 56）有关。方法所有家庭成员都接受了全面的眼科评估和多模式视网膜成像。两个视网膜异常的家族成员接受了额外的 OCT 血管造影、双波长自发荧光和荧光寿命成像眼底镜检查、动力性视力测定、眼底相关显微视力测定、视网膜电图和眼底电图检查。主要结果通过多模态成像：双波长自发荧光、荧光寿命、OCT 血管造影，描述 CYP2U1 变异患者的视网膜表型。C>T;p.(Gln315Ter)的两个兄弟姐妹的视网膜视网膜透明度下降，对蓝光有高反射性，黄斑色素重新分布到视网膜视网膜边缘，感光器缺失，荧光寿命成像眼底镜检查异常：与黄斑毛细血管扩张症 2 型（MacTel）的模式一致。其中一人从幼年起就有明显的神经系统异常，而第二个兄弟姐妹则没有神经系统异常。结论这些CYP2U1变体与MacTel的视网膜表型非常相似，提示这些疾病的病因和发病机制可能存在联系。

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