阿尔茨海默病(Alzheimer’s disease，AD)是发生于老年期或老年前期的中枢神经系统退行性病变，以进行性认知功能障碍为特征。随着社会老龄化加剧，AD已成为全球公共卫生问题，亟需研发更敏感、便捷和经济的筛查技术进行早期防控。眼球运动与认知功能密切相关，且眼球运动检查有非侵入性、成本低、检查时间短等优点。研究眼球运动异常和认知功能障碍之间的相关性，有助于研发更简便易操作的认知功能障碍筛查工具。随着人工智能技术的发展，机器学习算法强大的特征提取和计算能力对处理眼球运动检查结果有显著优势。本文对既往AD患者与眼球运动异常之间的相关性研究进行综述，并对机器学习算法模型辅助下，基于眼球运动异常模式进行认知功能障碍早期筛查技术开发的研究前景予以展望。
Alzheimer’s disease (AD) is a degenerative disease of the central nervous system that occurs in old age or early old age. It is characterized by progressive cognitive dysfunction. With the world population aging, AD has become a global public health problem. The development of a more sensitive, convenient, and economic screening technology for AD is urgently needed. The eye movement function is closely related to cognitive function. Moreover, eye movement examination has advantages including non-invasiveness, low cost, and short examination time. Researches on the correlation between abnormal eye movement and cognitive dysfunction can help to develop a simple and easy-to-use screening tool for cognitive dysfunction. With the development of artificial intelligence technology, the dominant feature extraction and computing capabilities of machine learning algorithms have a significant advantage in processing eye movement inspection results. This article reviews the correlation between AD and eye movement abnormalities aiming to provide the research prospects of early screening technology development for cognitive dysfunction based on abnormal eye movement with the application of machine learning models.
神经营养性角膜病变是一种与角膜神经退行性改变有关的疾病，表现为角膜神经的知觉和营养功能受损，导致角膜上皮缺损、角膜溃疡和角膜穿孔。目前对神经营养性角膜病变的主要治疗方式有药物治疗、非手术干预治疗和手术治疗，但是对于重度病变患者行药物治疗、非手术干预治疗通常效果不佳。对未恢复角膜神经营养功能的患者行角膜移植术，可能导致角膜移植术后上皮持续不愈合，因此恢复角膜神经营养功能是该类患者复明的重要前提。角膜神经移植术是重度神经营养性角膜病变患者恢复角膜神经营养功能，提高角膜知觉，改善角膜透明度的重要和有效的治疗方法。角膜神经移植术通过将具有正常功能的供体神经移植到麻痹眼角膜缘周围，使神经末梢重新长入角膜基质，恢复角膜知觉功能。随着角膜神经移植术的术式的不断改进，其良好的术后效果和优点已经渐渐凸显。文章基于作者结合团队在角膜神经移植术方面经验结合近年研究进展阐述了神经营养性角膜病变的治疗手段和不同术式在角膜神经移植术中的应用，并进行展望。
Neurotrophic keratopathy is a disease related to degenerative changes in corneal nerves, resulting in impaired sensory and nutritive functions of corneal nerves. This leads to corneal epithelial defects, corneal ulcers, and corneal perforation. Currently, the main treatment modalities include pharmacotherapy, non-surgical interventions, and surgical treatment. However, drug therapy and non-surgical interventions often yield unsatisfactory results for severe neurotrophic keratopathy patients. Performing corneal transplantation in patients with unrecovered corneal sensation may result in persistent epithelial defect. Therefore, the restoration of corneal sensation is a crucial prerequisite for visual rehabilitation. Corneal neurotization emerges as an important and effective therapeutic approach for severe cases of neurotrophic keratopathy, aiming to restore corneal sensation and enhance corneal transparency. The procedure involves transplanting nerves from a donor with normal sensory function to the paralyzed sub-Tenon perilimbal space, allowing nerve endings to regenerate into the corneal stroma and restoring corneal sensory function. With continuous improvements in the technique of corneal neurotization, its favorable postoperative outcomes and advantages are becoming increasingly evident. This article, based on the team's experience in corneal neurotization, elaborates on the treatment modalities for neurotrophic keratopathy and the application and prospects of various surgical techniques in corneal neurotization.
糖尿病性黄斑水肿(diabetic macular edema, DME)是糖尿病最常见和最严重的并发症之一，也是中青年劳动人群常见的致盲原因。DME病理生理机制复杂，是多种因素相互作用的结果，控制这些危险因素是降低发病率的关键。DME是全身病相关性眼病，其发生与发展受众多危险因素的影响，但此前文献对其总结不足，本文从全身因素及眼部因素两个方面就DME的危险因素进行综述。全身危险因素主要包括血糖控制欠佳、糖尿病病程长、高血压、血脂代谢紊乱、肥胖、肾功能异常、妊娠状态、降糖药物使用、贫血、阻塞性睡眠呼吸暂停低通气综合征、遗传因素、吸烟、饮酒、高血钙、低血镁等；而其眼部危险因素主要包括白内障、青光眼及玻璃体切割术、全视网膜激光光凝术、合并视网膜静脉阻塞和相关细胞因子等。深入认识和理解这些危险因素，有助于更好地预防和早期治疗DME，同时为治疗糖尿病视网膜病变过程中控制DME进展提供指引和参考。但是，其中一部分因素还存在一定争议，更多的DME危险因素仍有待进一步探索，期望在不久的将来，更多基础和前瞻性临床研究为DME危险因素及治疗提供高质量的证据。
Diabetic macular edema (DME) is one of the most common and severe complications of diabetes, and it is a leading cause of blindness in the working-age population. The pathophysiology of DME is complex, resulting from the interplay of various factors. Controlling these risk factors is crucial in reducing the incidence of DME. As a systemic diseaserelated ocular condition, the onset and progression of DME are influenced by numerous risk factors. However, previous literature has provided insufficient summaries of these factors. This review aims to summarize the risk factors for DME from both systemic and ocular perspectives. The systemic risk factors primarily include poor glycemic control, prolonged duration of diabetes, hypertension, dyslipidemia, obesity, renal dysfunction, pregnancy, the use of hypoglycemic medications, anemia, obstructive sleep apnea-hypopnea syndrome, genetic factors, smoking, alcohol consumption, hypercalcemia, and hypomagnesemia. On the other hand, ocular risk factors include cataracts, glaucoma and vitrectomy, panretinal photocoagulation, coexisting retinal vein occlusion, and related cytokines. A deeper understanding of these risk factors will aid in the better prevention and early treatment of DME, while also providing guidance and reference for controlling the progression of DME during the treatment of diabetic retinopathy. However, some of these factors remain controversial, and additional DME risk factors still need to be explored. It is hoped that, in the near future, morefoundational and prospective clinical studies will provide high-quality evidence on DME risk factors and treatments.
目的：探讨2003—2023年热休克蛋白(heat shock proteins,HSP)在眼科领域中的研究进展及前沿趋势。方法：利用Web of Science数据库检索2003年1月—2023年12月26日HSP在眼科领域的文献，采用文献计量学方法、应用VOSviewer及CiteSpaces软件对发文量、国家、机构、期刊、作者、关键词以及学科领域等数据进行定量分析及可视化。结果：共纳入1 079篇HSP在眼科领域的相关文献，总体发文量处于波动状态。美国(n =394)是发文量最多的国家，Investigative Ophthalmology & Visual Science(n =80)是发表相关文献最多的期刊。研究热点主要分为三部分，分别为青光眼发病机制、白内障发病机制及HSP在基因层面的眼科疾病机制研究。研究的前沿主题是青光眼、胆固醇、分子伴侣。生物化学与分子生物学、多学科材料科学和细胞生物学学科领域具有最高的中介中心性值，分别为0.60、0.28和0.26。多学科化学(爆发年份：2017—2023年；强度为6.3)是该领域研究前沿涉及的学科。结论：HSP在眼科领域的研究重点是揭示疾病的遗传背景，探究其在青光眼及白内障中的分子机制以及治疗应用。该领域分子机制研究的进展有赖于多学科的合作。
Objective: To investigate the advances and trends of heat shock proteins (HSP) in ophthalmology published from 2003 to 2023. Methods: The Web of Science database was used to retrieve the literature on heat shock proteins in ophthalmology published from January 1, 2003 to December 26, 2023. Bibliometric methods and VOSviewer and CiteSpaces software were used to analyze and visualize data, including publication count, countries, organizations, journals, authors, keywords and subject categories. Results: A total of 1079 publications related to HSP in ophthalmology were included, and the overall number of publications was fluctuating. The United States (n =394) was the leading contributor among countries. Investigative Ophthalmology & Visual Science (n =80) was the journal with the largest number of publications. The pathogenesis of glaucoma, the pathogenesis of cataract and the mechanism of ophthalmic diseases at the genetic level of HSP were identified as the research hotspots. Glaucoma, cholesterol, and molecular chaperones were identified as frontier research topics. Biochemistry & molecular biology, multidisciplinary materials science, and cell biology have the highest betweenness centrality values of 0.60, 0.28, and 0.26, respectively. Multidisciplinary chemistry (burst years: 2017 to 2023; strength = 6.3) was a subject involved in the research frontier of this field. Conclusion: Research on heat shock proteins in ophthalmology mainly focuses on revealing the genetic background of the diseases and exploring the molecular mechanisms and therapeutic applications in glaucoma and cataracts. The advance in the study on molecular mechanisms in this field depends on multidisciplinary collaboration.
铁离子在维持角膜细胞正常代谢、DNA合成和修复等生理活动中发挥关键作用，但过量的铁离子可能引发铁稳态失衡继而导致细胞毒性损伤和死亡。圆锥角膜是最常见的扩张性角膜疾病，其典型的Fleischer环是铁稳态失衡的直接证据。圆锥角膜与铁代谢相关的前期研究显示，铁稳态失衡有可能是诱发圆锥角膜发生和发展的潜在致病机制。文章总结了人体及角膜中正常的铁代谢循环以及圆锥角膜铁稳态失衡的证据，并从维持铁稳态角度出发探索可能的治疗策略，为扩张性眼病治疗提供新的思路。
Iron ions are essential for normal metabolism, DNA synthesis, and cellular repair in corneal cells. Nevertheless, an excess of these ions can disrupt iron homeostasis, leading to cellular toxicity, damage, and death. Keratoconus, the most prevalent ectatic corneal disorder, is often marked by the Fleischer ring, which indicates an imbalance in iron homeostasis. A review of early studies on keratoconus and iron metabolism suggests that this imbalance may be a potential pathogenic mechanism contributing to the onset and progression of the disease. This article aims to provide a comprehensive overview of normal iron metabolism in the human body and cornea, highlighting the evidence of iron homeostasis imbalance in keratoconus. It also explores potential therapeutic strategies focused on maintaining iron homeostasis, thereby offering novel insights into the treatment of ectatic eye diseases.
肥厚型脉络膜谱系疾病(pachychoroid disease spectrum,PCD)包括肥厚型脉络膜色素上皮病变(pachychoroid pigment epitheliopathy,PPE)、中心性浆液性脉络膜视网膜病变(central serous chorioretinopathy,CSC)、肥厚型脉络膜新生血管病变(pachychoroid neovasculopathy,PNV)、息肉样脉络膜血管病变(polypoidal choroidal vasculopathy,PCV)、局灶性脉络膜凹陷(focal choroidal excavation,FCE)和盘周肥厚型脉络膜综合征(peripapillary pachychoroid syndrome,PPS)。有学者将PCD看作脉络膜功能障碍引发的一系列连续疾病过程，但关于PCD的发病机制、形态改变尚未明确。该文对PCD的脉络膜、涡静脉及巩膜相关改变做一综述。
Pachychoroid disease spectrum include pachychoroid pigment epitheliopathy, central serous chorioretinopathy, pachychoroid neovasculopathy, polypoidal choroidal vasculopathy, focal choroidal excavation, and peripapillary pachychoroid syndrome. Currently, some scholars regard pachychoroid disease spectrum as a series of continuous disease processes caused by choroidal dysfunction, but the pathogenesis and morphological changes of pachychoroid disease spectrum are not yet clear. This paper reviews the changes of choroid, vortex veins and sclera in pachychoroid disease spectrum.
玻璃体替代物是玻璃体切割术后的必需品，用于填充玻璃体腔，恢复玻璃体的支撑视网膜、屈光和细胞屏障等功能。严重眼外伤及复杂视网膜脱离引起的视网膜/脉络膜脱离，如选用传统的玻璃体替代物(如硅油)填充，部分患者会出现硅油依赖眼或眼球萎缩，眼球难以保全。折叠式人工玻璃体球囊(foldable capsular vitreous body,FCVB)是我国独立研发的挽救眼球的人工玻璃体，属于国际首创，可以精细模拟自然玻璃体的结构，恢复玻璃体的部分功能。目前临床研究证实FCVB不仅可以有效避免硅油的并发症，还可以维持后房空间，缓慢恢复睫状体的功能，从而治疗硅油依赖眼，阻止眼球进一步萎缩。该文综述了FCVB的研究背景、结构特点、临床应用和拓展研究进展。
Vitreous substitutes are necessary after vitrectomy to fill the vitreous cavity and restore the vitreous to support retinal, refractive, and cellular barrier functions. Severe ocular trauma-induced retinal/choroidal detachment filled with traditional vitreous substitutes (e.g., silicone oil) can lead to silicone oil-dependent eyes and ocular atrophy in some patients, making it difficult to preserve the eye. Foldable capsular vitreous body (FCVB) is an artificial vitreous body independently developed in China to save the eye, which is the first of its kind in the world and can finely simulate the structure of natural vitreous body and restore some of the functions of vitreous body. It has been clinically proven that it can not only effectively avoid the complications of silicone oil, but also maintain the posterior chamber space and slowly restore the function of the ciliary body, thus treating silicone oil-dependent eyes and preventing further atrophy of the eye. This article reviews the research background, structural features, clinical applications and extended studies of FCVB.
随着光学相干断层扫描(optical coherence tomography,OCT)的快速发展和广泛应用，视盘周围高反射卵圆形团块样结构(peripapillary hyper-reflective ovoid mass-like structure,PHOMS)已成为神经眼科临床实践中OCT检查的常见征象之一。该结构是生理性改变还是病理性改变目前尚无定论，推测可能与视乳头轴浆瘀滞有关。该文针对PHOMS的形态特征做一综述，总结各种疾病相关的PHOMS，并提出一些针对PHOMS的疑点及研究方向，旨在为临床医生及早辨别PHOMS、早期治疗眼底疾病提供依据。
With the rapid development and widespread application of optical coherence tomography(OCT), peripapillary hyper-reflective ovoid mass-like structure (PHOMS) has become one of the common signs of OCT in neuro-ophthalmic clinical practice. Whether this structure is physiological or pathological has not been determined, and it is speculated that it may be related to the stagnation of the axial plasma of the optic papilla. In this review, we describe the morphological characteristics of PHOMS, summarize various diseases related to PHOMS, and proposes some doubtful points and research directions for PHOMS, aiming to provide evidence for clinicians to identify PHOMS as early as possible and treat fundus diseases in the early stage.
眼部移植物抗宿主病发生在超过一半的慢性移植物抗宿主病患者中，涉及眼表持续的炎症以及纤维化改变，最常见的表现为干燥性角膜结膜炎。严重的眼部移植物抗宿主病不但影响患者的工作和生活质量，同时也增加了其他眼部并发症的风险。慢性眼部移植物抗宿主病的治疗主要包括局部应用人工泪液、血清类制剂、抗炎药物等药物治疗，佩戴隐形眼镜、睑板腺按摩等物理治疗、封闭泪点、重建眼表等手术治疗。随着对眼部移植物抗宿主病发病机制的深入研究，许多新的治疗药物和治疗手段涌现临床。总结目前慢性眼部移植物抗宿主病在药物治疗、物理治疗、手术治疗方面的最新研究进展，将有助于为慢性眼部移植物抗宿主病的治疗带来更多选择和更新的研究思路。
More than half of the patients developed chronic graft-versus-host disease after accepting allogeneic hematopoietic stem cell transplantation suffer from ocular graft-versus-host disease. Ocular graft-versus-host disease involves persistent inflammation and fibrosis of the ocular surface and keratoconjunctivitis sicca is the most common symptom. Severe ocular graft-versus-host disease not only affects patients’ life quality, but also increases the risk of other ocular complications. The treatment of chronic ocular graft-versus-host disease mainly includes drug treatment, such as local application of artificial tears, serum eye drops and anti-inflammatory drugs; physical treatment, such as wearing contact lenses and meibomian gland massage; surgical treatment, such as punctal occlusion and reconstructing ocular surface. With the in-depth study of the pathogenesis of ocular graft-versus-host disease, many new therapeutic drugs and methods have emerged. Summarizing the latest research progress in drug, physical and surgical therapy of chronic ocular graft-versus-host disease will give us insights into treatment options and hot spot of research.
慢性移植物抗宿主病(chronic graft-versus-host disease，cGVHD)是骨髓移植后最具有破坏性并发症之一。移植物抗宿主病(graft-versus-host disease，GVHD)发生在10%~80%的造血干细胞移植(hematopoietic stem cell transplantation)受者中，而眼睛是人身体最脆弱的器官之一，有40%~60%接受HSCT的患者发生眼部GVHD，它主要影响泪腺、睑板腺、角膜和结膜等。cGVHD相关性干眼(dry eye associated with chronic graft-versus-host disease，cGVHD-DE)是眼部GVHD最多见的表现形式。cGVHD-DE的长期治疗因涉及多学科、多重结合治疗，至今仍然具有挑战性，其除了全身免疫抑制和眼部润滑剂外，通常还使用局部类固醇、环孢霉素和他克莫司滴眼液。针对中度和重度cGVHD-DE的治疗干预包括使用自体血清滴眼液和佩戴巩膜镜等，新兴起的治疗方案包括重链透明质酸 (heavy chain-hvaluronan/穿透素(pentraxin 3)结膜下注射、间充质基质细胞静脉注射、抑制纤维化药物等。
Chronic graft-versus-host disease (cGVHD) is one of the most devastating complications following bone marrow transplantation. GVHD develops in 10–80% of patients after hematopoietic stem cell transplantation (HSCT). The eye is one of the most vulnerable organs of the human body. Ocular GVHD occurs in 40–60% of patients with GVHD undergoing HSCT, and it mostly affects the lacrimal glands, meibomian glands, cornea, and conjunctiva. The most common form of ocular GVHD is dry eye disease (DED). The long-term treatment of cGVHD-related dry eye syndrome remains challenging and involves a multidisciplinary approach. Besides systemic immunosuppression and ocular lubricants, topical steroids, topical cyclosporine, and topical tacrolimus are commonly prescribed. Newer therapeutic interventions for moderate and severe cGVHD-related DED include using serum eye drops and scleral contact lenses. Emerging treatment options include subconjunctival injection of heavy chain-hyaluronan (HC-HA)/ pentraxin 3 (PTX3), intravenous injection of mesenchymal stromal cells, antifibrotic drugs, etc. This article reviews the mechanisms, clinical findings, and treatment of cGVHD-related dry eye syndrome.
