Progress in Retinal and Eye Research最新文献_第9页

Cellular component transfer between photoreceptor cells of the retina 视网膜感光细胞之间的细胞成分转移。

IF 18.6 1区医学 Q1 OPHTHALMOLOGY

Progress in Retinal and Eye Research

Pub Date : 2024-11-16 DOI: 10.1016/j.preteyeres.2024.101317

Joyce Wang , Patrick O. Nnoromele , Ying V. Liu , Robert J. Johnston Jr. , Mandeep S. Singh

Photoreceptor transplantation is a potential therapeutic strategy for degenerative retinal diseases. Studies on mechanisms contributing to retinal regeneration and vision repair identified cellular components transfer (CCT) as playing a role, in addition to somatic augmentation (referred to as “cell replacement” in this paper). In CCT, donor photoreceptors shuttle proteins, RNA, and mitochondria to host photoreceptors through intercellular connections. The discovery of CCT in the transplantation context triggered a re-interpretation of prior transplantation studies that generally did not include specific CCT assays and thereby broadly emphasized the cell replacement model, reflecting the prevailing understanding of retinal transplantation biology at that time. In addition to clarifying our understanding of photoreceptor biology, CCT has raised the possibility of developing treatments to replenish molecular deficiencies in diseased photoreceptor cells. As the CCT field evolves, investigators have used diverse terminology, and implemented different CCT assays following transplantation in animal models. The non-standardized terminology of CCT and absent minimal assay standards for detection can hinder communication between investigators and comparison between studies. In this review, we discuss the current understanding of CCT, provide an overview of transplantation and regeneration studies in small and large animals, and propose terminology and a minimal assay standard for CCT. Further research on CCT may eventually provide new avenues to treat a range of hereditary and acquired retinopathies while illuminating mechanisms of cell-cell interaction in the retina.

光感受器移植是一种潜在的视网膜退化性疾病治疗策略。对视网膜再生和视力修复机制的研究发现，除了体细胞增殖（本文中称为 "细胞替代"）外，细胞成分转移（CCT）也发挥着作用。在CCT中，供体感光细胞通过细胞间连接将蛋白质、核糖核酸和线粒体穿梭到宿主感光细胞。CCT在移植中的发现引发了对之前移植研究的重新解读，之前的移植研究一般不包括特定的CCT检测，因此广泛强调细胞置换模型，这反映了当时对视网膜移植生物学的普遍理解。除了澄清我们对感光细胞生物学的认识外，CCT 还为开发治疗方法以补充病变感光细胞的分子缺陷提供了可能性。随着CCT领域的发展，研究人员使用了不同的术语，并在动物模型移植后实施了不同的CCT检测。CCT 术语的非标准化和缺乏最低检测标准会阻碍研究者之间的交流和研究之间的比较。在这篇综述中，我们讨论了目前对 CCT 的理解，概述了小动物和大动物的移植和再生研究，并提出了 CCT 的术语和最低检测标准。对CCT的进一步研究最终可能为治疗一系列遗传性和获得性视网膜病变提供新的途径，同时阐明视网膜中细胞-细胞相互作用的机制。

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引用次数: 0

Role of epigenetics in corneal health and disease 表观遗传学在角膜健康和疾病中的作用。

IF 18.6 1区医学 Q1 OPHTHALMOLOGY

Progress in Retinal and Eye Research

Pub Date : 2024-11-14 DOI: 10.1016/j.preteyeres.2024.101318

Swati Sood , Anil Tiwari , Jyoti Sangwan , Mehak Vohra , Nishant R. Sinha , Ratnakar Tripathi , Virender S. Sangwan , Rajiv R. Mohan

Epigenetics plays a vital role in corneal health and diseases. Epigenetic changes regulate the expression of genes by altering the accessibility of chromatin via histone modifications, DNA methylation and miRNAs without altering DNA sequence. Ocular trauma and infections are common causes of corneal damage, vision impairment, and mono/bilateral blindness worldwide. Mounting literature shows that epigenetic modifications can modulate corneal clarity, function, and pathogenesis including inflammation, wound healing, fibrosis, and neovascularization. Additionally, epigenetic modifications can be targeted to reverse corneal pathologies and develop interventional therapies. However, current understanding on how epigenetic modifications lead to corneal abnormalities and diseases is limited. This review provides in-depth knowledge and mechanistic understanding of epigenetics alterations in corneal pathogenesis, and information on potential epigenetic targets for treatment of corneal diseases.

表观遗传学在角膜健康和疾病中发挥着至关重要的作用。表观遗传学变化通过组蛋白修饰、DNA 甲基化和 miRNA 改变染色质的可及性，从而调节基因的表达，而不改变 DNA 序列。眼外伤和感染是全球角膜损伤、视力损伤和单/双侧失明的常见原因。越来越多的文献表明，表观遗传修饰可调节角膜的清晰度、功能和发病机制，包括炎症、伤口愈合、纤维化和新生血管。此外，表观遗传修饰可作为逆转角膜病变和开发介入疗法的靶点。然而，目前对表观遗传修饰如何导致角膜异常和疾病的了解还很有限。本综述将深入介绍表观遗传学改变在角膜发病机制中的作用和机理，并介绍治疗角膜疾病的潜在表观遗传学靶点。

引用次数: 0

Dual inheritance patterns: A spectrum of non-syndromic inherited retinal disease phenotypes with varying molecular mechanisms 双重遗传模式：具有不同分子机制的非综合征遗传性视网膜疾病表型谱。

IF 18.6 1区医学 Q1 OPHTHALMOLOGY

Progress in Retinal and Eye Research

Pub Date : 2024-10-31 DOI: 10.1016/j.preteyeres.2024.101308

Lara K. Holtes, Suzanne E. de Bruijn, Frans P.M. Cremers, Susanne Roosing

Inherited retinal diseases (IRDs) encompass a variety of disease phenotypes and are known to display both clinical and genetic heterogeneity. A further complexity is that for several IRD-associated genes, pathogenic variants have been reported to cause either autosomal dominant (AD) or autosomal recessive (AR) diseases. The possibility of dual inheritance can create a challenge for variant interpretation as well as the genetic counselling of patients. This review aims to determine whether the molecular mechanisms behind the dual inheritance of each IRD-associated gene is well established, not yet properly understood, or if the association is questionable. Each gene is discussed individually in detail due to different protein structures and functions, but there are overlapping characteristics. For example, eight genes only have a limited number of reported pathogenic variants or a hotspot region implicated in the second inheritance pattern. Whereas CRX and RP1 display distinct spatial patterns for AR and AD pathogenic variants based on the variant type and/or location. The genes with a questionable dual inheritance, namely AIPL1, CRB1, and RCBTB1 highlight the importance of carefully considering allele frequency data. Finally, the crucial role relevant functional studies in animal and cell models play in validating a variant's biochemical or molecular effect is emphasised.

遗传性视网膜疾病（IRDs）包括多种疾病表型，已知其临床和遗传均具有异质性。更复杂的是，据报道，一些 IRD 相关基因的致病变异可导致常染色体显性（AD）或常染色体隐性（AR）疾病。双重遗传的可能性给变异解释和患者遗传咨询带来了挑战。本综述旨在确定每个 IRD 相关基因的双重遗传背后的分子机制是已经确立，还是尚未得到正确理解，或者这种关联是否值得怀疑。由于每个基因的蛋白质结构和功能各不相同，我们将逐一对其进行详细讨论，但每个基因都有重叠的特点。例如，有 8 个基因只报告了数量有限的致病变体或与第二种遗传模式有关的热点区域。而 CRX 和 RP1 则根据变异类型和/或位置显示出 AR 和 AD 致病变异的不同空间模式。AIPL1、CRB1 和 RCBTB1 等具有可疑双重遗传性的基因凸显了仔细考虑等位基因频率数据的重要性。最后，强调了动物和细胞模型中的相关功能研究在验证变异体的生化或分子效应方面所起的关键作用。

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引用次数: 0

Eye on the horizon: The metabolic landscape of the RPE in aging and disease 地平线上的眼睛：老化和疾病中 RPE 的代谢状况。

IF 18.6 1区医学 Q1 OPHTHALMOLOGY

Progress in Retinal and Eye Research

Pub Date : 2024-10-19 DOI: 10.1016/j.preteyeres.2024.101306

David S. Hansman , Jianhai Du , Robert J. Casson , Daniel J. Peet

To meet the prodigious bioenergetic demands of the photoreceptors, glucose and other nutrients must traverse the retinal pigment epithelium (RPE), a polarised monolayer of cells that lie at the interface between the outer retina and the choroid, the principal vascular layer of the eye. Recent investigations have revealed a metabolic ecosystem in the outer retina where the photoreceptors and RPE engage in a complex exchange of sugars, amino acids, and other metabolites. Perturbation of this delicate metabolic balance has been identified in the aging retina, as well as in age-related macular degeneration (AMD), the leading cause of blindness in the Western world. Also common in the aging and diseased retina are elevated levels of cytokines, oxidative stress, advanced glycation end-products, increased growth factor signalling, and biomechanical stress – all of which have been associated with metabolic dysregulation in non-retinal cell types and tissues. Herein, we outline the role of these factors in retinal homeostasis, aging, and disease. We discuss their effects on glucose, mitochondrial, lipid, and amino acid metabolism in tissues and cell types outside the retina, highlighting the signalling pathways through which they induce these changes. Lastly, we discuss promising avenues for future research investigating the roles of these pathological conditions on retinal metabolism, potentially offering novel therapeutic approaches to combat age-related retinal disease.

为了满足光感受器巨大的生物能需求，葡萄糖和其他营养物质必须穿过视网膜色素上皮（RPE），RPE 是位于视网膜外层和脉络膜（眼睛的主要血管层）之间的极化单层细胞。最近的研究揭示了视网膜外层的新陈代谢生态系统，感光器和 RPE 在其中进行着复杂的糖、氨基酸和其他代谢物的交换。这种微妙的新陈代谢平衡已在老化的视网膜以及老年性黄斑变性（AMD）中被发现受到干扰，而老年性黄斑变性是西方世界失明的主要原因。在老化和患病的视网膜中，细胞因子、氧化应激、高级糖化终产物、生长因子信号增加和生物力学应激水平升高也很常见，所有这些都与非视网膜细胞类型和组织的代谢失调有关。在此，我们将概述这些因素在视网膜稳态、衰老和疾病中的作用。我们将讨论它们对视网膜以外组织和细胞类型中葡萄糖、线粒体、脂质和氨基酸代谢的影响，并重点介绍它们诱导这些变化的信号通路。最后，我们讨论了未来研究这些病理条件对视网膜新陈代谢的作用的前景广阔的途径，这有可能为防治与年龄有关的视网膜疾病提供新的治疗方法。

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引用次数: 0

Pathobiology of the crystalline lens in Stickler syndrome 施蒂克勒综合征晶状体的病理生物学。

IF 18.6 1区医学 Q1 OPHTHALMOLOGY

Progress in Retinal and Eye Research

Pub Date : 2024-09-29 DOI: 10.1016/j.preteyeres.2024.101304

Martin P. Snead , Frank J. Lovicu , Thomas RW. Nixon , Allan J. Richards , Howard Martin

Purpose

The Stickler syndromes are a group of connective tissue disorders characterised by congenital myopia, giant retinal tear and retinal detachment, cleft palate, hearing loss and premature arthropathy. Patients with Stickler syndrome are also susceptible to abnormalities of the crystalline lens. Since neither type II or type XI collagen (those typically affected in the vast majority of Stickler patients) are highly expressed in the lens, this observational cohort study explores potential alternative mechanisms to explain why patients frequently exhibit such unusual but characteristic types of cataract.

Methods

Author observations drawn from a cohort of over 1800 patients with genetically confirmed Stickler syndrome.

Results

3 distinct lens pathologies were identified. Firstly, a congenital quadrantic lamellar opacity. This can be present in both type 1 (COL2A1) and type 2 (COL11A1) Stickler syndrome. Secondly, early onset Pantone 557 C blue-green nuclear cataract. Thirdly, congenital lens coloboma associated with localised zonule deficiency.

Conclusions

The characteristic quadrantic lamellar lens opacity can be helpful in alerting to the possible diagnosis, particularly in sub-groups with an ocular-only phenotype.

Temporal and spatial signalling pathways shared embryologically by both the developing vitreous body and crystalline lens suggest an ancillary role of the fibrillar collagens in cell signalling beyond their basic structural function. A common pathway of TGFβ/BMP super-family dysregulation may be shared with allied disorders associated with both retinal detachment and cataract as well as the pathobiology linking retinal detachment and cataract in the population at large.

Congenital lens coloboma associated with localised zonule deficiency can increase the difficulty and risks of cataract surgery. Strategies to mitigate such risks are presented.

目的：斯蒂克勒综合征是一组结缔组织疾病，其特征是先天性近视、巨大视网膜撕裂和视网膜脱离、腭裂、听力损失和早发性关节病。斯蒂克勒综合征患者还容易出现晶状体异常。由于 II 型或 XI 型胶原蛋白（绝大多数斯蒂克勒综合征患者的典型患病类型）在晶状体中的表达量都不高，因此本观察性队列研究探讨了潜在的替代机制，以解释为什么患者经常表现出这种不寻常但具有特征性的白内障类型：作者从 1800 多名经基因证实的斯蒂克勒综合征患者中进行观察：结果：发现了三种不同的晶状体病变。首先是先天性四联片状混浊。1 型（COL2A1）和 2 型（COL11A1）Stickler 综合征患者都可能出现这种情况。第二，早发性 Pantone 557 C 蓝绿色核白内障。第三，先天性晶状体软骨瘤，伴有局部小叶缺失：结论：特征性的四象限片状晶状体不透明有助于警惕可能的诊断，尤其是在仅有眼部表型的亚组中。发育中的玻璃体和晶状体在胚胎学上共享的时间和空间信号通路表明，纤维胶原在细胞信号传导中发挥着基本结构功能之外的辅助作用。TGFb/BMP超家族失调的共同途径可能与视网膜脱离和白内障的相关疾病以及视网膜脱离和白内障的病理生物学相关。先天性晶状体色素瘤伴有局部小叶缺失，会增加白内障手术的难度和风险。本文介绍了降低此类风险的策略。

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引用次数: 0

AI in the clinical management of GA: A novel therapeutic universe requires novel tools 人工智能在 GA 临床管理中的应用：新的治疗领域需要新的工具。

IF 18.6 1区医学 Q1 OPHTHALMOLOGY

Progress in Retinal and Eye Research

Pub Date : 2024-09-27 DOI: 10.1016/j.preteyeres.2024.101305

Gregor S. Reiter, Julia Mai, Sophie Riedl, Klaudia Birner, Sophie Frank, Hrvoje Bogunovic, Ursula Schmidt-Erfurth

Regulatory approval of the first two therapeutic substances for the management of geographic atrophy (GA) secondary to age-related macular degeneration (AMD) is a major breakthrough following failure of numerous previous trials. However, in the absence of therapeutic standards, diagnostic tools are a key challenge as functional parameters in GA are hard to provide. The majority of anatomical biomarkers are subclinical, necessitating advanced and sensitive image analyses. In contrast to fundus autofluorescence (FAF), optical coherence tomography (OCT) provides high-resolution visualization of neurosensory layers, including photoreceptors, and other features that are beyond the scope of human expert assessment. Artificial intelligence (AI)-based methodology strongly enhances identification and quantification of clinically relevant GA-related sub-phenotypes. Introduction of OCT-based biomarker analysis provides novel insight into the pathomechanisms of disease progression and therapeutic, moving beyond the limitations of conventional descriptive assessment. Accordingly, the Food and Drug Administration (FDA) has provided a paradigm-shift in recognizing ellipsoid zone (EZ) attenuation as a primary outcome measure in GA clinical trials. In this review, the transition from previous to future GA classification and management is described. With the advent of AI tools, diagnostic and therapeutic concepts have changed substantially in monitoring and screening of GA disease. Novel technology combined with pathophysiological knowledge and understanding of the therapeutic response to GA treatments, is currently opening the path for an automated, efficient and individualized patient care with great potential to improve access to timely treatment and reduce health disparities.

首批两种治疗老年性黄斑变性（AMD）继发性地理萎缩（GA）的药物获得了监管部门的批准，这是继之前多项试验失败后的又一重大突破。然而，在缺乏治疗标准的情况下，诊断工具是一项关键挑战，因为很难提供 GA 的功能参数。大多数解剖生物标志物都是亚临床的，需要先进而灵敏的图像分析。与眼底自动荧光（FAF）相比，光学相干断层扫描（OCT）可提供神经感觉层（包括光感受器）的高分辨率可视化，以及超出人类专家评估范围的其他特征。基于人工智能（AI）的方法大大提高了临床相关 GA 亚表型的识别和量化能力。基于 OCT 的生物标记分析为疾病进展和治疗的病理机制提供了新的见解，超越了传统描述性评估的局限性。因此，美国食品和药物管理局（FDA）将椭球带（EZ）衰减作为GA临床试验的主要结果测量指标，实现了范式的转变。在这篇综述中，描述了从以前到未来的 GA 分类和管理的转变。随着人工智能工具的出现，在监测和筛查 GA 疾病方面，诊断和治疗理念发生了重大变化。新技术与病理生理学知识和对 GA 治疗反应的理解相结合，目前正在为自动化、高效和个性化的患者护理开辟道路，在提高及时治疗的可及性和减少健康差异方面具有巨大潜力。

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引用次数: 0

The relationship between intraocular pressure and glaucoma: An evolving concept 眼压与青光眼的关系：一个不断演变的概念。

IF 18.6 1区医学 Q1 OPHTHALMOLOGY

Progress in Retinal and Eye Research

Pub Date : 2024-09-19 DOI: 10.1016/j.preteyeres.2024.101303

Sanjay G. Asrani , Elyse J. McGlumphy , Lama A. Al-Aswad , Craig J. Chaya , Shan Lin , David C. Musch , Ian Pitha , Alan L. Robin , Barbara Wirostko , Thomas V. Johnson

Intraocular pressure (IOP) is the most important modifiable risk factor for glaucoma and fluctuates considerably within patients over short and long time periods. Our field's understanding of IOP has evolved considerably in recent years, driven by tonometric technologies with increasing accuracy, reproducibility, and temporal resolution that have refined our knowledge regarding the relationship between IOP and glaucoma risk and pathogenesis. The goal of this article is to review the published literature pertinent to the following points: 1) the factors that determine IOP in physiologic and pathologic states; 2) technologies for measuring IOP; 3) scientific and clinical rationale for measuring diverse IOP metrics in patients with glaucoma; 4) the impact and shortcomings of current standard-of-care IOP monitoring approaches; 5) recommendations for approaches to IOP monitoring that could improve patient outcomes; and 6) research questions that must be answered to improve our understanding of how IOP contributes to disease progression. Retrospective and prospective data, including that from landmark clinical trials, document greater IOP fluctuations in glaucomatous than healthy eyes, tendencies for maximal daily IOP to occur outside of office hours, and, in addition to mean and maximal IOP, an association between IOP fluctuation and glaucoma progression that is independent of mean in-office IOP. Ambulatory IOP monitoring, measuring IOP outside of office hours and at different times of day and night, provides clinicians with discrete data that could improve patient outcomes. Eye care clinicians treating glaucoma based on isolated in-office IOP measurements may make treatment decisions without fully capturing the entire IOP profile of an individual. Data linking home blood pressure monitors and home glucose sensors to dramatically improved outcomes for patients with systemic hypertension and diabetes and will be reviewed as they pertain to the question of whether ambulatory tonometry is positioned to do the same for glaucoma management. Prospective randomized controlled studies are warranted to determine whether remote tonometry-based glaucoma management might reduce vision loss and improve patient outcomes.

眼内压（IOP）是青光眼最重要的可改变风险因素，在患者体内的短期和长期波动都很大。近年来，眼压测量技术的准确性、可重复性和时间分辨率不断提高，完善了我们对眼压与青光眼风险和发病机制之间关系的认识。本文旨在回顾与以下几点相关的已发表文献：1) 生理和病理状态下决定眼压的因素；2) 测量眼压的技术；3) 测量青光眼患者各种眼压指标的科学和临床依据；4) 当前标准护理眼压监测方法的影响和不足；5) 可改善患者预后的眼压监测方法建议；6) 必须回答的研究问题，以提高我们对眼压如何导致疾病进展的认识。回顾性和前瞻性数据（包括来自具有里程碑意义的临床试验的数据）显示，青光眼患者的眼压波动比健康眼更大，每日最大眼压往往发生在非诊室时间，而且除了平均和最大眼压外，眼压波动与青光眼进展之间也存在关联，这种关联与诊室平均眼压无关。非卧床眼压监测可在非办公时间、白天和晚上的不同时段测量眼压，为临床医生提供离散数据，从而改善患者的治疗效果。眼科临床医生在治疗青光眼时，可能会根据诊室内的孤立眼压测量结果做出治疗决定，而无法全面了解患者的整个眼压状况。将家用血压计和家用血糖传感器与显著改善全身性高血压和糖尿病患者的治疗效果联系起来的数据，将与非卧床眼压测量是否能为青光眼治疗带来同样效果的问题联系起来进行审查。有必要进行前瞻性随机对照研究，以确定基于远程眼压测量的青光眼管理是否可以减少视力损失并改善患者的治疗效果。

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引用次数: 0

Ocular adverse events associated with antibody-drug conjugates used in cancer: Focus on pathophysiology and management strategies 与癌症中使用的抗体药物共轭物相关的眼部不良反应：病理生理学和管理策略。

IF 18.6 1区医学 Q1 OPHTHALMOLOGY

Progress in Retinal and Eye Research

Pub Date : 2024-09-18 DOI: 10.1016/j.preteyeres.2024.101302

Eric E. Gabison , Antoine Rousseau , Marc Labetoulle , Anas Gazzah , Benjamin Besse

Antibody-drug conjugates (ADCs) are designed to maximize cancer cell death with lower cytotoxicity toward noncancerous cells and are an increasingly valuable option for targeted cancer therapies. However, anticancer treatment with ADCs may be associated with ocular adverse events (AEs) such as dry eye, conjunctivitis, photophobia, blurred vision, and corneal abnormalities. While the pathophysiology of ADC-related ocular AEs has not been fully elucidated, most ocular AEs are attributed to off-target effects. Product labelling for approved ADCs includes drug-specific guidance for dose modification and management of ocular AEs; however, limited data are available regarding effective strategies to minimize and mitigate ocular AEs. Overall, the majority of ocular AEs are reversible through dose modification or supportive care. Eye care providers play key roles in monitoring patients receiving ADC therapy for ocular signs and symptoms to allow for the early detection of ADC-related ocular AEs and to ensure the timely administration of appropriate treatment. Therefore, awareness is needed to help ophthalmologists to identify treatment-related ocular AEs and provide effective management in collaboration with oncologists as part of the patient's cancer care team. This review provides an overview of ocular AEs that may occur with approved and investigational ADC anticancer treatments, including potential underlying mechanisms for ADC-related ocular AEs. It also discusses clinical management practices relevant to ophthalmologists for prevention, monitoring, and management of ADC-related ocular AEs. In collaboration with oncologists, ophthalmologists play a vital role in caring for patients with cancer by assisting with the prompt recognition, mitigation, and management of treatment-related ocular AEs.

抗体-药物共轭物（ADCs）旨在最大程度地杀死癌细胞，同时降低对非癌细胞的细胞毒性，是一种越来越有价值的癌症靶向疗法。然而，使用 ADCs 进行抗癌治疗可能会引起眼部不良反应（AEs），如干眼症、结膜炎、畏光、视力模糊和角膜异常。虽然 ADC 相关眼部不良反应的病理生理学尚未完全阐明，但大多数眼部不良反应可归因于脱靶效应。已获批准的 ADC 的产品标签包括剂量调整和眼部 AE 管理的特定药物指导；然而，有关最大限度减少和缓解眼部 AE 的有效策略的数据有限。总体而言，通过剂量调整或支持性护理，大多数眼部 AE 是可逆的。眼科护理人员在监测接受 ADC 治疗的患者的眼部体征和症状方面发挥着关键作用，以便及早发现 ADC 相关的眼部 AE，并确保及时给予适当的治疗。因此，我们需要提高认识，帮助眼科医生识别与治疗相关的眼部 AE，并与作为患者癌症护理团队一部分的肿瘤科医生合作提供有效的管理。本综述概述了已批准和正在研究的 ADC 抗癌治疗可能出现的眼部 AE，包括 ADC 相关眼部 AE 的潜在潜在机制。它还讨论了眼科医生在预防、监测和管理 ADC 相关眼部 AE 方面的临床管理实践。眼科医生与肿瘤科医生合作，通过协助及时识别、缓解和管理与治疗相关的眼部 AE，在护理癌症患者方面发挥着重要作用。

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引用次数: 0

The role of CFTR in the eye, and the effect of early highly effective modulator treatment for cystic fibrosis on eye health CFTR 在眼睛中的作用，以及早期高效调节剂治疗囊性纤维化对眼睛健康的影响。

IF 18.6 1区医学 Q1 OPHTHALMOLOGY

Progress in Retinal and Eye Research

Pub Date : 2024-09-06 DOI: 10.1016/j.preteyeres.2024.101299

Elena K. Schneider-Futschik , Yimin Zhu , Danni Li , Mark D. Habgood , Bao N. Nguyen , Ines Pankonien , Margarida D. Amaral , Laura E. Downie , Holly R. Chinnery

Cystic fibrosis transmembrane conductance regulator (CFTR) is a protein that plays a crucial role in various human organs, including the respiratory and digestive systems. Dysfunctional CFTR is the key variant of the lethal genetic disorder, cystic fibrosis (CF). In the past decade, highly effective CFTR modulator therapies, including elexacaftor-tezacaftor-ivacaftor, have revolutionised CF management by correcting the underlying molecular defect to improve patient outcomes and life expectancy. Despite demonstrating multiorgan efficacy, clinical studies have largely overlooked the potential for ocular disturbances with CFTR modulator therapy, with the exception of a few case studies reporting the presence of crystalline lens pathologies in young children on CFTR modulators, and in breastfed infants born to individuals who were on CFTR modulator treatment during pregnancy. CFTR is present in multiple tissues during embryonic development, including the eye, and its expression can be influenced by genetic and environmental factors. This review summarises the role of CFTR in the eye, and the potential impact of CFTR on eye function and vision later in life. This information provides a framework for understanding the use and possible effects of CFTR-modulating therapeutics in the context of eye health, including the potential to leverage the eye for non-invasive and accessible diagnostic and monitoring capabilities in patients with CF.

囊性纤维化跨膜传导调节因子（CFTR）是一种蛋白质，在呼吸系统和消化系统等多个人体器官中发挥着至关重要的作用。CFTR 功能失调是致命性遗传疾病囊性纤维化（CF）的关键变体。在过去十年中，包括 elexacaftor-tezacaftor-ivacaftor 在内的高效 CFTR 调节器疗法通过纠正潜在的分子缺陷，改善了患者的预后和预期寿命，从而彻底改变了 CF 的治疗方法。尽管CFTR调节剂具有多器官疗效，但临床试验在很大程度上忽视了CFTR调节剂治疗可能导致的眼部病变，只有少数病例研究报告了服用CFTR调节剂的幼儿和孕期服用CFTR调节剂的母乳喂养婴儿出现晶状体病变。在胚胎发育过程中，CFTR 存在于包括眼睛在内的多种组织中，其表达会受到遗传和环境因素的影响。本综述总结了 CFTR 在眼球发育过程中可能发挥的作用，以及 CFTR 对日后眼球功能和视力的潜在影响。这些信息提供了一个框架，有助于了解在眼部健康方面使用调节 CFTR 的疗法及其可能产生的影响，包括利用眼部对 CF 患者进行非侵入性、无障碍诊断和监测的潜力。

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引用次数: 0

Optical coherence tomography angiography of the retina and choroid in systemic diseases 系统性疾病中视网膜和脉络膜的光学相干断层血管造影。

IF 18.6 1区医学 Q1 OPHTHALMOLOGY

Progress in Retinal and Eye Research

Pub Date : 2024-08-30 DOI: 10.1016/j.preteyeres.2024.101292

Jacqueline Chua , Bingyao Tan , Damon Wong , Gerhard Garhöfer , Xin Wei Liew , Alina Popa-Cherecheanu , Calvin Woon Loong Chin , Dan Milea , Christopher Li-Hsian Chen , Leopold Schmetterer

Optical coherence tomography angiography (OCTA) has transformed ocular vascular imaging, revealing microvascular changes linked to various systemic diseases. This review explores its applications in diabetes, hypertension, cardiovascular diseases, and neurodegenerative diseases. While OCTA provides a valuable window into the body's microvasculature, interpreting the findings can be complex. Additionally, challenges exist due to the relative non-specificity of its findings where changes observed in OCTA might not be unique to a specific disease, variations between OCTA machines, the lack of a standardized normative database for comparison, and potential image artifacts. Despite these limitations, OCTA holds immense potential for the future. The review highlights promising advancements like quantitative analysis of OCTA images, integration of artificial intelligence for faster and more accurate interpretation, and multi-modal imaging combining OCTA with other techniques for a more comprehensive characterization of the ocular vasculature. Furthermore, OCTA's potential future role in personalized medicine, enabling tailored treatment plans based on individual OCTA findings, community screening programs for early disease detection, and longitudinal studies tracking disease progression over time is also discussed. In conclusion, OCTA presents a significant opportunity to improve our understanding and management of systemic diseases. Addressing current limitations and pursuing these exciting future directions can solidify OCTA as an indispensable tool for diagnosis, monitoring disease progression, and potentially guiding treatment decisions across various systemic health conditions.

光学相干断层血管成像（OCTA）改变了眼部血管成像，揭示了与各种系统性疾病相关的微血管变化。这篇综述探讨了它在糖尿病、高血压、心血管疾病和神经退行性疾病中的应用。虽然 OCTA 为观察人体微血管提供了一个宝贵的窗口，但解释这些发现可能很复杂。此外，由于 OCTA 研究结果的相对非特异性（在 OCTA 中观察到的变化可能并非特定疾病所独有）、OCTA 机器之间的差异、缺乏用于比较的标准化标准数据库以及潜在的图像伪影等原因，OCTA 的研究也面临着挑战。尽管存在这些局限性，OCTA 在未来仍有巨大潜力。这篇综述强调了一些很有前景的进展，如对 OCTA 图像进行定量分析，整合人工智能以实现更快、更准确的解读，以及将 OCTA 与其他技术相结合的多模式成像，以更全面地描述眼部血管的特征。此外，还讨论了 OCTA 未来在个性化医疗中的潜在作用，即根据个人的 OCTA 检查结果、社区早期疾病检测筛查计划和随时间推移跟踪疾病进展的纵向研究，提供量身定制的治疗方案。总之，OCTA 为提高我们对全身性疾病的认识和管理提供了一个重要机会。解决目前的局限性并寻求这些令人兴奋的未来发展方向，可以使 OCTA 成为诊断、监测疾病进展和指导各种系统性健康问题治疗决策的不可或缺的工具。

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