Progress in Retinal and Eye Research最新文献_第6页

Understanding glaucoma as astrocyte-driven neurodegeneration in the optic nerve head: an integrative clinicopathological perspective 理解青光眼作为视神经头星形细胞驱动的神经变性：一个综合的临床病理观点

IF 18.6 1区医学 Q1 OPHTHALMOLOGY

Progress in Retinal and Eye Research

Pub Date : 2025-07-01 Epub Date: 2025-06-13 DOI: 10.1016/j.preteyeres.2025.101379

Eun Jung Lee , Do Young Park , Jong Chul Han , Changwon Kee

Glaucoma is characterized by the progressive loss of retinal ganglion cells (RGCs), primarily driven by axonal degeneration within the optic nerve head (ONH). Recent advances in neurodegeneration and neuroinflammation research have opened new astrocyte-centered perspectives on glaucoma pathogenesis. Critical evaluation of emerging evidence suggests that ONH astrocyte changes may serve as the primary driver of pathogenesis, with loss of astrocytic support playing a substantial role. Evidence from experimental glaucoma models reveals that early intraocular pressure (IOP)-induced remodeling of the ONH astrocyte network precedes RGC axonal damage, potentially mediated by impaired astrocytic control of electrophysiological homeostasis within the surrounding extracellular space. Furthermore, the heterogeneous glia-neuron ratio (GNR) across the normal human ONH lamina cribrosa exhibits an inverse topographic association with the spatiotemporal pattern of regional vulnerability observed clinically in glaucoma, suggesting that regional variations in the astrocyte-to-neuron ratio, reflecting astrocytic support reserve, may critically determine local tissue susceptibility to glaucomatous stress. Recent optical coherence tomography–based insights into the regional vulnerability in human glaucoma are discussed. This clinicopathological interpretation may offer a comprehensive framework that coherently integrates diverse neurodegenerative mechanisms into a unified clinical entity, bridge the conventional mechanical and ischemic theories of glaucoma by highlighting astrocyte changes as a common primary target of risk factors, and ultimately redefine glaucoma as astrocyte-driven neurodegeneration in the biomechanically and bioenergetically vulnerable ONH.

青光眼的特点是视网膜神经节细胞（RGCs）的进行性丧失，主要是由视神经头（ONH）内的轴突变性引起的。神经变性和神经炎症研究的最新进展为以星形胶质细胞为中心的青光眼发病机制开辟了新的视角。对新证据的批判性评估表明，ONH星形胶质细胞的变化可能是发病机制的主要驱动因素，星形胶质细胞支持的丧失起着重要作用。来自青光眼实验模型的证据表明，早期眼压（IOP）诱导的ONH星形胶质细胞网络重塑先于RGC轴突损伤，可能是由周围细胞外空间星形胶质细胞对电生理稳态的控制受损介导的。此外，在青光眼临床观察中，正常人ONH网层的异质胶质-神经元比率（GNR）与区域易感性时空模式呈负相关，表明星形细胞-神经元比率的区域差异反映了星形细胞支持储备，可能在很大程度上决定了局部组织对青光眼应激的易感性。最近的光学相干断层扫描为基础的见解，在人类青光眼的区域脆弱性进行了讨论。这种临床病理解释可能提供一个全面的框架，将多种神经退行性机制整合到一个统一的临床实体中，通过突出星形细胞变化作为危险因素的共同主要目标，将青光眼的传统力学和缺血性理论联系起来，并最终将青光眼重新定义为生物力学和生物能量易感的ONH中星形细胞驱动的神经退行性变。

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引用次数: 0

Pachychoroid disease spectrum: how multimodal imaging and OCT angiography have improved our knowledge 厚脉络膜疾病谱：多模态成像和OCT血管造影如何提高我们的知识。

IF 18.6 1区医学 Q1 OPHTHALMOLOGY

Progress in Retinal and Eye Research

Pub Date : 2025-07-01 Epub Date: 2025-05-23 DOI: 10.1016/j.preteyeres.2025.101372

Pasquale Viggiano , Giacomo Boscia , Elham Sadeghi , Gemmy Cheung , Enrico Borrelli , Giovanni Alessio , Jay Chhablani , Francesco Boscia

Pachychoroid spectrum disorders (PSDs) represent a group of chorioretinal disorders characterized by abnormal choroidal thickening and various pathological changes in the choroid, retinal pigment epithelium, and retina. This review provides a comprehensive analysis of current multimodal imaging techniques in the diagnosis and management of PSDs. We examine the role of various imaging modalities including optical coherence tomography (OCT), OCT angiography (OCTA), en face OCT, fluorescein angiography (FA), indocyanine green angiography (ICGA), infrared imaging (IR), and fundus autofluorescence (FAF) in evaluating PSDs. Each imaging modality provides unique insights: OCT reveals characteristic choroidal thickening and structural changes; OCTA demonstrates alterations in choroidal flow and neovascularization; en face OCT allows detailed visualization of choroidal vasculature and intervortex anastomoses; FA shows patterns of leakage; ICGA reveals choroidal hyperpermeability and pachyvessels; IR imaging assists in RPE evaluation; and FAF highlights RPE dysfunction. The integration of these imaging techniques has enhanced our understanding of the pathophysiology of PSDs and improved our ability to diagnose, monitor, and treat these conditions. This review particularly emphasizes how OCTA has advanced our knowledge of choroidal circulation and neovascularization in PSDs. We also discuss future directions in imaging technology and their potential impact on personalized therapeutic approaches, including optimized photodynamic therapy based on imaging biomarkers. The synergistic use of multimodal imaging represents a cornerstone in the management of PSDs, enabling more precise diagnosis and tailored treatment strategies.

厚脉络膜谱系疾病（psd）是一组以脉络膜异常增厚和脉络膜、视网膜色素上皮和视网膜的各种病理改变为特征的脉络膜视网膜疾病。本文综述了目前多模态成像技术在psd诊断和治疗中的应用。我们研究了各种成像方式的作用，包括光学相干断层扫描（OCT）、OCT血管造影（OCTA）、表面OCT、荧光素血管造影（FA）、吲哚菁绿血管造影（ICGA）、红外成像（IR）和眼底自身荧光（FAF）在评估psd中的作用。每种成像方式都提供了独特的见解：OCT显示特征性脉络膜增厚和结构变化；OCTA显示脉络膜血流和新生血管的改变；正面OCT可以详细显示脉络膜血管系统和漩涡间吻合；FA显示渗漏模式；ICGA显示脉络膜高通透性和血管粗大；红外成像有助于RPE评估；FAF则突出了RPE功能障碍。这些成像技术的整合增强了我们对psd病理生理学的理解，提高了我们诊断、监测和治疗这些疾病的能力。这篇综述特别强调了OCTA如何提高了我们对psd脉络膜循环和新生血管的认识。我们还讨论了成像技术的未来方向及其对个性化治疗方法的潜在影响，包括基于成像生物标志物的优化光动力治疗。多模态成像的协同使用是psd管理的基石，可以实现更精确的诊断和量身定制的治疗策略。

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引用次数: 0

Pericytes in the optic nerve head 视神经头的周细胞。

IF 18.6 1区医学 Q1 OPHTHALMOLOGY

Progress in Retinal and Eye Research

Pub Date : 2025-07-01 Epub Date: 2025-05-29 DOI: 10.1016/j.preteyeres.2025.101375

Susannah Waxman , Deborah Villafranca-Baughman , Julie Phillippi , Tatjana C. Jakobs , Luis Alarcon-Martinez , Adriana Di Polo , Ian A. Sigal

Pericytes are a unique population of contractile mural cells and are an essential part of the microvasculature. In the retina and brain, pericytes play crucial roles in regulating blood flow, maintaining the blood-brain barrier, signaling with neighboring cells, and depositing extracellular matrix. Pericyte dysfunction is an early process in a variety of neurodegenerative conditions. However, remarkably little is known about pericytes at an early site of neurodegeneration in glaucoma, the optic nerve head (ONH). This work summarizes the current understanding of pericyte contributions to ONH physiology, identifies potential roles in glaucomatous pathophysiology, and uncovers open questions at the intersection of these areas. We surveyed the literature to identify the roles of ONH pericytes in the context of health and glaucoma. Additionally, we probed for the presence of pericytes along microvasculature in mouse, nonhuman primate, and human donor ONH tissues. We identified an association between factors influencing ONH dysfunction in glaucoma and factors influencing pericyte dysfunction in other neurodegenerative conditions. Pericytes exist in the mouse, nonhuman primate, and human ONH, implicating their capacity for local function. ONH pericytes represent a promising but underexplored target for treating microvascular impairment in glaucoma. Investigating the contribution of pericytes in both healthy and disease states can help inform mechanisms of dysfunction in glaucomatous pathology, paving the way for the development of novel therapeutic strategies.

周细胞是一种独特的可收缩壁细胞群，是微血管系统的重要组成部分。在视网膜和大脑中，周细胞在调节血流、维持血脑屏障、与邻近细胞传递信号和沉积细胞外基质等方面起着至关重要的作用。周细胞功能障碍是各种神经退行性疾病的早期过程。然而，对于青光眼神经退行性变的早期部位——视神经头（ONH）的周细胞，我们所知甚少。这项工作总结了目前对周细胞对ONH生理的贡献的理解，确定了青光眼病理生理的潜在作用，并揭示了这些领域交叉的开放性问题。我们调查了文献，以确定ONH周细胞在健康和青光眼的背景下的作用。此外，我们在小鼠、非人灵长类动物和人类ONH供体组织中检测了微血管周围细胞的存在。我们发现影响青光眼ONH功能障碍的因素与影响其他神经退行性疾病周细胞功能障碍的因素之间存在关联。周细胞存在于小鼠、非人灵长类动物和人类ONH中，暗示它们具有局部功能的能力。ONH周细胞是治疗青光眼微血管损伤的一个有希望但尚未开发的靶点。研究周细胞在健康和疾病状态下的作用可以帮助了解青光眼病理功能障碍的机制，为开发新的治疗策略铺平道路。

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引用次数: 0

The march to harmonized imaging standards for retinal imaging 视网膜成像统一成像标准的推进。

IF 18.6 1区医学 Q1 OPHTHALMOLOGY

Progress in Retinal and Eye Research

Pub Date : 2025-07-01 Epub Date: 2025-05-11 DOI: 10.1016/j.preteyeres.2025.101363

Nayoon Gim , Alina N. Ferguson , Marian Blazes , Cecilia S. Lee , Aaron Y. Lee

The adoption of standardized imaging protocols in retinal imaging is critical to overcoming challenges posed by fragmented data formats across devices and manufacturers. The lack of standardization hinders clinical interoperability, collaborative research, and the development of artificial intelligence (AI) models that depend on large, high-quality datasets. The Digital Imaging and Communication in Medicine (DICOM) standard offers a robust solution for ensuring interoperability in medical imaging. Although DICOM is widely utilized in radiology and cardiology, its adoption in ophthalmology remains limited. Retinal imaging modalities such as optical coherence tomography (OCT), fundus photography, and OCT angiography (OCTA) have revolutionized retinal disease management but are constrained by proprietary and non-standardized formats.

This review underscores the necessity for harmonized imaging standards in ophthalmology, detailing DICOM standards for retinal imaging including ophthalmic photography (OP), OCT, and OCTA, and their requisite metadata information. Additionally, the potential of DICOM standardization for advancing AI applications in ophthalmology is explored. A notable example is the Artificial Intelligence Ready and Equitable Atlas for Diabetes Insights (AI-READI) dataset, the first publicly available standards-compliant DICOM retinal imaging dataset. This dataset encompasses diverse retinal imaging modalities, including color fundus photography, infrared, autofluorescence, OCT, and OCTA. By leveraging multimodal retinal imaging, AI-READI provides a transformative resource for studying diabetes and its complications, setting a blueprint for future datasets aimed at harmonizing imaging formats and enabling AI-driven breakthroughs in ophthalmology. Our manuscript also addresses challenges in retinal imaging for diabetic patients, retinal imaging-based AI applications for studying diabetes, and potential advancements in retinal imaging standardization.

在视网膜成像中采用标准化成像协议对于克服设备和制造商之间碎片化数据格式带来的挑战至关重要。缺乏标准化阻碍了临床互操作性、协作研究以及依赖于大型高质量数据集的人工智能（AI）模型的开发。医学数字成像和通信（DICOM）标准为确保医学成像的互操作性提供了一个强大的解决方案。虽然DICOM在放射学和心脏病学中得到了广泛的应用，但在眼科中的应用仍然有限。视网膜成像方式，如光学相干断层扫描（OCT）、眼底摄影和OCT血管造影（OCTA）已经彻底改变了视网膜疾病的管理，但受到专有和非标准化格式的限制。这篇综述强调了协调眼科成像标准的必要性，详细介绍了包括眼科摄影（OP）、OCT和OCTA在内的视网膜成像DICOM标准及其必要的元数据信息。此外，还探讨了DICOM标准化在推进人工智能在眼科应用方面的潜力。一个值得注意的例子是糖尿病洞察人工智能准备和公平地图集（AI-READI）数据集，这是第一个公开可用的符合标准的DICOM视网膜成像数据集。该数据集包含多种视网膜成像方式，包括彩色眼底摄影，红外，自体荧光，OCT和OCTA。通过利用多模态视网膜成像，AI-READI为研究糖尿病及其并发症提供了变革性的资源，为未来的数据集制定了蓝图，旨在协调成像格式，并使人工智能驱动的眼科突破成为可能。我们的手稿还讨论了糖尿病患者视网膜成像的挑战，基于视网膜成像的人工智能应用于糖尿病研究，以及视网膜成像标准化的潜在进展。

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引用次数: 0

Genetic architecture of congenital cataracts: correlation of pathogenic variants with morphology and clinical outcomes 先天性白内障的遗传结构：致病变异与形态学和临床结果的相关性。

IF 18.6 1区医学 Q1 OPHTHALMOLOGY

Progress in Retinal and Eye Research

Pub Date : 2025-07-01 Epub Date: 2025-05-29 DOI: 10.1016/j.preteyeres.2025.101373

Dongwei Guo , Yi Jiang , Yuxi Zheng , Shiqiang Li , Guangming Jin , Xueshan Xiao , Xiaoyun Jia , Wenmin Sun , Danying Zheng , James Fielding Hejtmancik , Qingjiong Zhang

Congenital cataract (CC) refers to lens opacity presented at birth, posing considerable challenges to early childhood visual development and lifelong visual impairment. Although a substantial proportion of CC cases arise from genetic defects, significant gaps remain in the understanding of the genotype-phenotype correlations and the characteristics of potentially pathogenic variants associated with this condition. In the current study, the genetic architecture of CC was investigated by a comparative literature review of 39 known CC-associated genes from Cat-map and HGMD, within an in-house cohort of 150 CC families, complemented by comparing with in-house exome sequencing data from 10,530 families with various eye conditions as well as data from the gnomAD database. Comparative analysis revealed: 1) The in-house genetic diagnostic yield was 63.3% (95/150); 2) Variants in specific genes were correlated with distinct phenotypes, especially for variants in BFSP2, MIP, GJA3, PITX3 and CRYGD; 3) GJA3 variants were often associated with high myopia, and CRYGC variants were often linked to microcornea or microphthalmia; 4) A predominance of CRYAA, LIM2 and MIP variants involve arginine to cysteine changes, and CRYGD variants involve proline to threonine changes; 5) The interpretation of variant pathogenicity is a great challenge. Uncertain variants in CC are present in up to 56.0% of the general population. In conclusion, identified monogenic variants contribute to approximately two-thirds of CC, which has been underestimated as one-third before. These findings broaden the current understanding of the genotype-phenotype relationships in CC and underscore the importance of precise genetic classification for effective diagnosis and management. Further exploration of these genetic factors may provide new insights into prevention and treatment strategies for CC.

先天性白内障（Congenital cataract， CC）是指出生时晶状体混浊，对儿童早期视力发育和终身视力损害构成相当大的挑战。尽管很大一部分CC病例是由遗传缺陷引起的，但在了解基因型-表型相关性以及与此相关的潜在致病变异的特征方面仍存在重大差距。在目前的研究中，通过比较文献综述来自Cat-map和HGMD的39个已知CC相关基因，在150个CC家族的内部队列中，通过比较10530个不同眼病家族的内部外显子组测序数据以及gnomAD数据库的数据，研究了CC的遗传结构。对比分析表明：1)内部遗传诊断率为63.3% (95/150)；2)特定基因的变异与不同的表型相关，特别是BFSP2、MIP、GJA3、PITX3和CRYGD的变异；3) GJA3变异常与高度近视相关，CRYGC变异常与小角膜或小眼相关；4) CRYAA、LIM2和MIP变异主要涉及精氨酸到半胱氨酸的变化，CRYGD变异主要涉及脯氨酸到苏氨酸的变化；5)变异致病性的解释是一个巨大的挑战。不确定的CC变异存在于高达56.0%的普通人群中。总之，确定的单基因变异贡献了大约三分之二的CC，这在以前被低估为三分之一。这些发现拓宽了目前对CC基因型-表型关系的理解，并强调了精确的遗传分类对有效诊断和管理的重要性。进一步探索这些遗传因素可能为CC的预防和治疗策略提供新的见解。

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引用次数: 0

Unravelling CYP4V2: Clinical features, genetic insights, pathogenic mechanisms and therapeutic strategies in Bietti crystalline corneoretinal dystrophy 解开CYP4V2: Bietti晶体角膜视网膜营养不良的临床特征、遗传见解、致病机制和治疗策略

IF 18.6 1区医学 Q1 OPHTHALMOLOGY

Progress in Retinal and Eye Research

Pub Date : 2025-07-01 Epub Date: 2025-06-05 DOI: 10.1016/j.preteyeres.2025.101377

Ruixuan Jia , Shaohong Chen , Wang Li , Jinlu Zhang , Baoyuan Qu , Jing Qiao , Xiang Meng , Shicheng Yu , Xiaozhen Liu , Boling Xu , Tianjin Chen , Xiuping Shen , Wenmin Sun , Hongliang Dou , Vinit B. Mahajan , Qiongjiong Zhang , Liping Yang

Inherited retinal dystrophies (IRDs) comprise a spectrum of disease phenotypes with genetic heterogeneity and clinical phenotypic diversity. Bietti crystalline corneoretinal dystrophy (BCD) represents a distinct IRD subtype characterized by crystalline deposits in the retina. Although rare in Western populations, BCD ranks among the most prevalent IRDs in East Asia, affecting an estimated 124,000 to 377,000 individuals worldwide. As a severe type of IRD, BCD demonstrates accelerated progression and currently lacks effective treatment. The BCD disease is caused by a biallelic mutation in the CYP4V2 gene. With a coding sequence (CDS) of 1,578 bp, CYP4V2 can be effectively encapsulated into adeno-associated virus (AAV) vectors. As a hydroxylase, CYP4V2 is mainly expressed in retinal pigment epithelial (RPE) cells, which can be transduced by AAVs and are suitable for gene augmentation therapy that replaces the function of mutant proteins. Given the large patient population, severe visual impairment, and feasibility of gene therapy, several research groups are interested in developing gene therapy products for BCD, and two products entering Phase III clinical trials have made significant progress. This review outlines the clinical features, genetic insights and pathogenic mechanisms of BCD and discusses the ongoing gene therapy clinical trials, including efficacy and concerns. This knowledge will help us bridge the gap between molecular studies and clinical treatments, facilitating translation from bench to bedside. We believe that advancements in BCD gene therapy will inform the treatment of other IRDs.

遗传性视网膜营养不良症（IRDs）包括一系列具有遗传异质性和临床表型多样性的疾病表型。Bietti结晶性角膜视网膜营养不良（BCD）是一种独特的IRD亚型，其特征是视网膜中的结晶沉积。虽然在西方人群中很少见，但BCD是东亚最常见的鸟类之一，全球估计有12.4万至37.7万人受到影响。作为一种严重的IRD类型，BCD表现出加速进展，目前缺乏有效的治疗方法。BCD疾病是由CYP4V2基因的双等位基因突变引起的。CYP4V2编码序列（CDS）为1578 bp，可以有效地封装到腺相关病毒（AAV）载体中。CYP4V2作为一种羟化酶，主要表达于视网膜色素上皮（RPE）细胞中，可被aav转导，适用于替代突变蛋白功能的基因增强治疗。鉴于BCD患者群体大、视力障碍严重以及基因治疗的可行性，多个研究小组对开发BCD基因治疗产品感兴趣，有两个产品已进入III期临床试验，取得了重大进展。本文综述了BCD的临床特点、遗传学见解和致病机制，并讨论了正在进行的基因治疗临床试验，包括疗效和关注的问题。这些知识将帮助我们弥合分子研究和临床治疗之间的差距，促进从实验室到床边的转化。我们相信BCD基因治疗的进展将为其他ird的治疗提供参考。

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引用次数: 0

Advances and therapeutic opportunities in visual cycle modulation 视觉周期调节的进展和治疗机会

IF 18.6 1区医学 Q1 OPHTHALMOLOGY

Progress in Retinal and Eye Research

Pub Date : 2025-05-01 Epub Date: 2025-04-23 DOI: 10.1016/j.preteyeres.2025.101360

Jordan Zaluski , Marco Bassetto , Philip D. Kiser , Gregory P. Tochtrop

The visual cycle is a metabolic pathway that enables continuous vision by regenerating the 11-cis-retinal chromophore for photoreceptors opsins. Although integral to normal visual function, the flux of retinoids through this cycle can contribute to a range of retinal pathologies, including Stargardt disease, age-related macular degeneration, and diabetic retinopathy. In such conditions, intermediates and byproducts of the visual cycle, such as bisretinoid components of lipofuscin, can accumulate, concomitant with cellular damage and eventual photoreceptor loss. This has inspired efforts to modulate the visual cycle, aiming to slow or prevent the formation of these toxic intermediates and thus preserve retinal structure and function. Over the past two decades, multiple strategies to modulate the visual cycle have emerged. These include both intrinsic approaches, targeting key enzymes, retinoid-binding proteins, or receptors within the pigment epithelium or photoreceptors (e.g., RPE65, CRBP1, and rhodopsin inhibitors/antagonists) and extrinsic strategies that indirectly alter retinoid availability within the retina (e.g., RBP4 antagonists). Many of these agents have shown promise in animal models of visual cycle-associated retinal diseases, reducing pathological changes, and improving retinal survival. Several have advanced into clinical studies, although none are currently FDA-approved. Challenges remain in optimizing drug specificity and duration of action while minimizing side effects such as nyctalopia. In this review, we comprehensively examine current and emerging visual cycle modulators, discuss their medicinal chemistry, mechanisms of action, efficacy in preclinical and clinical studies, and highlight future opportunities for drug discovery aimed at safely and effectively preserving vision through modulation of this biochemical pathway.

视觉循环是一种代谢途径，通过再生光感受器视蛋白的11-顺式视网膜发色团来实现连续视觉。尽管类维甲酸是正常视觉功能的组成部分，但在这个循环中，类维甲酸的流动可导致一系列视网膜病变，包括Stargardt病、年龄相关性黄斑变性和糖尿病性视网膜病变。在这种情况下，视觉循环的中间体和副产物，如脂褐素的类双维甲酸成分，可以积累，伴随细胞损伤和最终的光感受器丧失。这激发了调节视觉周期的努力，旨在减缓或阻止这些有毒中间体的形成，从而保持视网膜的结构和功能。在过去的二十年里，出现了多种调节视觉周期的策略。这些方法包括内在方法，针对关键酶、类视黄酮结合蛋白或色素上皮或光感受器内的受体（例如，RPE65、CRBP1和视紫红质抑制剂/拮抗剂）和间接改变视网膜内类视黄酮可用性的外在策略（例如，RBP4拮抗剂）。许多这些药物在视觉周期相关视网膜疾病的动物模型中显示出希望，减少病理改变，提高视网膜存活率。有几种已经进入临床研究，尽管目前没有一种获得fda批准。挑战仍然是优化药物特异性和作用时间，同时尽量减少副作用，如夜盲症。在这篇综述中，我们全面研究了当前和新兴的视觉周期调节剂，讨论了它们的药物化学、作用机制、临床前和临床研究中的疗效，并强调了未来通过调节这一生化途径安全有效地保护视力的药物发现机会。

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引用次数: 0

En face OCT: Breakthroughs in understanding the pathoanatomy of retinal disease and clinical applications En face OCT：视网膜疾病病理解剖及临床应用的突破。

IF 18.6 1区医学 Q1 OPHTHALMOLOGY

Progress in Retinal and Eye Research

Pub Date : 2025-05-01 Epub Date: 2025-03-05 DOI: 10.1016/j.preteyeres.2025.101351

Alessandro Feo , Prithvi Ramtohul , Andrea Govetto , Enrico Borrelli , Riccardo Sacconi , Giulia Corradetti , Giuseppe Querques , Mario R. Romano , Philip J. Rosenfeld , Richard F. Spaide , K Bailey Freund , SriniVas Sadda , David Sarraf

En face optical coherence tomography (OCT) is a practical and informative imaging modality to noninvasively visualize distinct retinal and choroidal layers by providing coronal images using boundary-specific segmentation. Ongoing research with this method is generating breakthroughs in the illustration of new perspectives of retinal disease. The clinical value of en face OCT as an advanced retinal imaging tool is growing steadily and it has unveiled many new insights into the pathoanatomy of retinal disorders. Moreover, this modality can capture various en face OCT biomarkers that correspond to different cell or tissue subtypes, which were previously only identified through histological or electron microscopy methods, underscoring the significance of this technique in providing valuable pathoanatomical information.

In this comprehensive review, we will systematically summarize the en face OCT findings across a broad spectrum of retinal diseases, including disorders of the vitreoretinal interface and retinal vascular system (e.g. paracentral acute middle maculopathy or PAMM and diabetic retinopathy), in addition to the en face OCT features of other conditions such as age-related macular degeneration, pachychoroid disease spectrum, myopic degeneration, uveitis and inflammatory disorders, inherited retinal dystrophies, and drug toxicity. We will discuss and highlight the unique clinical and pathoanatomical findings uncovered with en face OCT of each these diseases mentioned above.

面部光学相干断层扫描（OCT）是一种实用且信息丰富的成像方式，通过使用边界特定分割提供冠状图像，可以无创地可视化不同的视网膜和脉络膜层。这种方法正在进行的研究在视网膜疾病的新视角方面取得了突破。作为一种先进的视网膜成像工具，正面OCT的临床价值正在稳步增长，并为视网膜疾病的病理解剖提供了许多新的见解。此外，这种模式可以捕获各种表面OCT生物标志物，这些生物标志物对应于不同的细胞或组织亚型，这些生物标志物以前只能通过组织学或电子显微镜方法识别，强调了该技术在提供有价值的病理解剖学信息方面的重要性。在这篇全面的综述中，我们将系统地总结广泛的视网膜疾病的表面OCT发现，包括玻璃体视网膜界面和视网膜血管系统疾病（如中央旁急性中黄斑病变或PAMM和糖尿病视网膜病变），以及其他疾病的表面OCT特征，如年龄相关性黄斑变性、厚脉络膜疾病谱、近视变性、葡萄膜炎和炎症性疾病。遗传性视网膜营养不良和药物毒性。我们将讨论并强调上述每种疾病的正面OCT所发现的独特临床和病理解剖结果。

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引用次数: 0

Gene Therapy-Associated Uveitis (GTAU): Understanding and mitigating the adverse immune response in retinal gene therapy 基因治疗相关性葡萄膜炎（GTAU）：了解和减轻视网膜基因治疗中的不良免疫反应。

IF 18.6 1区医学 Q1 OPHTHALMOLOGY

Progress in Retinal and Eye Research

Pub Date : 2025-05-01 Epub Date: 2025-03-14 DOI: 10.1016/j.preteyeres.2025.101354

Ryan Purdy , Molly John , Alissa Bray , Alison J. Clare , David A. Copland , Ying Kai Chan , Robert H. Henderson , Fanny Nerinckx , Bart P. Leroy , Paul Yang , Mark E. Pennesi , Robert E. MacLaren , M Dominik Fischer , Andrew D. Dick , Kanmin Xue

Retinal gene therapy using adeno-associated viral (AAV) vectors has been a groundbreaking step-change in the treatment of inherited retinal diseases (IRDs) and could also be used to treat more common retinal diseases such as age-related macular degeneration and diabetic retinopathy. The delivery and expression of therapeutic transgenes in the eye is limited by innate and adaptive immune responses against components of the vector product, which has been termed gene therapy-associated uveitis (GTAU). This is clinically important as intraocular inflammation could lead to irreversible loss of retinal cells, deterioration of visual function and reduced durability of treatment effect associated with a costly one-off treatment. For retinal gene therapy to achieve an improved efficacy and safety profile for treating additional IRDs and more common diseases, the risk of GTAU must be minimised. We have collated insights from pre-clinical research, clinical trials, and the real-world implementation of AAV-mediated retinal gene therapy to help understand the risk factors for GTAU. We draw attention to an emerging framework, which includes patient demographics, vector construct, vector dose, route of administration, and choice of immunosuppression regime. Importantly, we consider efforts to date and potential future strategies to mitigate the adverse immune response across each of these domains. We advocate for more targeted immunomodulatory approaches to the prevention and treatment of GTAU based on better understanding of the underlying immune response.

利用腺相关病毒（AAV）载体进行视网膜基因治疗是遗传性视网膜疾病（IRDs）治疗的突破性进展，也可用于治疗更常见的视网膜疾病，如年龄相关性黄斑变性和糖尿病性视网膜病变。治疗性转基因在眼内的传递和表达受到针对载体产物成分的先天和适应性免疫反应的限制，这被称为基因治疗相关性葡萄膜炎（GTAU）。这在临床上具有重要意义，因为眼内炎症可导致视网膜细胞不可逆转的丧失，视觉功能恶化，并且与昂贵的一次性治疗相关的治疗效果的持久性降低。为了使视网膜基因疗法在治疗更多的ird和更常见的疾病方面获得更好的疗效和安全性，必须将GTAU的风险降至最低。我们从临床前研究、临床试验和aav介导的视网膜基因治疗的实际实施中整理了见解，以帮助了解GTAU的危险因素。我们提请注意一个新兴的框架，其中包括患者人口统计学，载体结构，载体剂量，给药途径和免疫抑制方案的选择。重要的是，我们考虑了迄今为止的努力和潜在的未来策略，以减轻这些领域的不良免疫反应。我们提倡在更好地了解潜在免疫反应的基础上，采用更有针对性的免疫调节方法来预防和治疗GTAU。

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引用次数: 0

Glands of Moll: history, current knowledge and their role in ocular surface homeostasis and disease Moll腺体：历史、当前知识及其在眼表稳态和疾病中的作用

IF 18.6 1区医学 Q1 OPHTHALMOLOGY

Progress in Retinal and Eye Research

Pub Date : 2025-05-01 Epub Date: 2025-05-05 DOI: 10.1016/j.preteyeres.2025.101362

Michael Stopfer , Ingrid Zahn , Katharina Jüngert , Gerhard Aumüller , Frans L. Moll , Martin Schicht , Helen P. Makarenkova , Cintia S. de Paiva , Friedrich P. Paulsen

Over the last 20 years, research into the Meibomian glands of the eyelids has increased exponentially and is now widely recognized as a field of research. It is all the more astonishing that knowledge about another type of gland in the eyelids, the Moll glands or ciliary glands, has almost stagnated and there has been little to almost no progress, even though this type of gland as a whole takes up a relatively large volume in the upper and lower eyelids. There is not much information about the namesake Moll or the function of the glands although these are listed in nearly every textbook of anatomy, histology and ophthalmology. For this reason, we set out to compile the existing knowledge about the Moll glands of the eyelids in order to create a basis for follow-up studies and to stimulate research into this type of gland. In our literature research, we went back to the middle of the 19th century and made contact with a descendant of the Moll family and illustrate their relevance for the present. The structure of the secretory part of the Moll glands is very well described, a number of secretory products are known, but the current state of research allows only very rough speculations about their function. The overview provides numerous interesting insights, which, however, raise more questions than they provide answers.

在过去的20年里，对眼睑睑板腺的研究呈指数增长，现在被广泛认为是一个研究领域。更令人惊讶的是，关于眼睑中另一种腺体，即毛囊腺或纤毛腺的知识几乎停滞不前，几乎没有任何进展，尽管这种类型的腺体作为一个整体在上眼睑和下眼睑中占据了相对较大的体积。尽管几乎所有的解剖学、组织学和眼科学教科书都列出了与Moll同名的腺体或其功能，但关于这些腺体的信息并不多。出于这个原因，我们开始汇编关于眼睑的Moll腺的现有知识，以便为后续研究创造基础，并刺激对这种类型的腺体的研究。在我们的文献研究中，我们回到了19世纪中叶，并与Moll家族的一位后裔取得了联系，并说明了他们与现在的相关性。Moll腺分泌部分的结构被很好地描述，许多分泌产物是已知的，但目前的研究状态只允许对它们的功能进行非常粗略的推测。概述提供了许多有趣的见解，然而，这些见解提出的问题比提供的答案更多。

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引用次数: 0