2024年4月 第39卷 第4期

主管:中华人民共和国教育部
主办:中山大学
承办:中山大学中山眼科中心
主编:林浩添
论著

双模态全视场光学相干层析技术的角膜缘高分辨率成像

High-resolution imaging of limbus tissue with dual-mode full-field optical coherence tomography

:169-179
 
目的:开发细胞级高分辨率、结构与功能一体化的双模态全视场光学相干层析系统(full-field optical coherence tomography,FFOCT),实现角膜缘组织的双模态FFOCT成像。方法:基于Linnik干涉成像原理,利用高数值孔径显微物镜(NA=0.8)及高速平面互补金属氧化物半导体(complementary metal oxide semiconductor,CMOS)相机,设计搭建高分辨率的组织静态结构和内源动态功能成像一体化双模态FFOCT系统;构建基于四相位调制结构影像提取及时域干涉信号动态频谱分析的功能影像重建算法;对人供体角膜缘组织开展各深度层的双模式FFOCT成像有效性验证。结果:搭建的双模态FFOCT成像系统可实现横向分辨率0.5 μ m,轴向分辨率1.7 μ m,成像视野320 μ m×320 μ m,相机采集速度100 Hz。系统实现角膜缘组织无外源标记情况下的细胞级分辨率三维结构和内源功能成像,FFOCT静态结构影像清晰显示角膜缘上皮、Vogt栅栏、隐窝、基质、血管及淋巴管等结构,FFOCT动态功能影像突出显示了代谢活跃细胞(角膜缘上皮细胞、免疫细胞等)。结论:双模态FFOCT高分辨率成像系统可提供角膜缘微观结构和活细胞无标记内源功能可视化信息,将为角膜缘疾病的研究及临床诊疗提供全新的成像分析技术。
Objective: To develop a cellular-level, high-resolution, integrated dual-modal full-field optical coherence tomography (FFOCT) system capable of simultaneously imaging the structure and function of limbus tissue. Methods: Utilizing the Linnik interference imaging principle, a high-resolution dual-modal FFOCT system was designed and constructed using a high numerical aperture (NA=0.8) microscope objective and a high-speed flat CMOS camera. A functional imaging reconstruction algorithm based on four-phase modulation structure image extraction and dynamic frequency spectrum analysis of temporal interference signals was developed. The effectiveness of dual-mode FFOCT imaging at various depth layers of human corneal limbal tissue was validated. Results: The constructed dual-modal FFOCT imaging system achieved lateral resolution of 0.5 μ m, axial resolution of 1.7 μ m, imaging field of view of 320 μ m × 320 μ m, and camera acquisition speed of 100 Hz. The system enabled cellular-level resolution three-dimensional structural and intrinsic functional imaging of corneal limbal tissue without exogenous labeling. Static structural FFOCT images clearly displayed limbal epithelium, palisades of Vogt, crypts, stroma, blood vessels, and lymphatic vessels, while dynamic functional FFOCT images highlighted metabolically active cells (limbal epithelial cells, immune cells, etc.). Conclusion: The dual-modal FFOCT high-resolution imaging system provides visualization of corneal limbal microstructural and live cell intrinsic functional information without labeling, offering a novel imaging analysis technique for research and clinical diagnosis and treatment of limbal diseases.

利用可穿戴设备监测学龄儿童量化用眼行为并定量分析近视发生相关因素

Wearable device in monitoring children's quantitative visual behavior and quantitative analysis of risks related to myopia

:180-187
 
目的:探索一种无创的、智能可穿戴设备监测学龄儿童量化的用眼行为,并定量分析近视发生的相关因素。方法:招募佛山市禅城区石湾第二小学三年级及狮城中学小学部五年级的年龄为7~11岁部分学生共171例。所有受试者均按照非睫状肌麻痹主觉验光结果分为近视组108例和非近视组63例,所有受试者均佩戴智能可穿戴设备“云夹”,进行为期10 d(2022年9月21日—2022年10月2日)的用眼行为数据(近距离用眼距离、近距离用眼时间、近距离环境光照、有效户外时间)采集。采用t检验比较近视组与非近视组儿童在用眼行为数据之间的差异,并应用Logistic回归分析用眼行为与近视发生的相关性。绘制受试者操作特征(receiver operating characteristic curve,ROC)曲线,并计算曲线下面积(area undercurve,AUC)分析用眼行为习惯对近视发生的预测价值。结果:学龄期儿童近视患病率为63.2%。近视组与非近视组在每天用眼时间、单次用眼时间、用眼距离、白天用眼光照、晚上用眼光照、每天户外活动时间及每天有效户外活动暴露次数比较差异均有统计学意义(均P<0.05)。Logistic回归分析显示,单次用眼时间、每天用眼时间是近视发生的危险因素。Spearman相关性分析显示,单次用眼时间及每天用眼时间均与近视发生呈正相关(均P<0.05)。单次用眼时间预测近视发生的ROC曲线下面积为0.939。结论:可穿戴设备“云夹”可量化学龄期儿童用眼行为;学龄期儿童近视发生可能与近距离用眼时间有一定相关性;预测模型可结合儿童屈光发育档案,量化近视发生风险,对儿童实现分类管理,及时采取个性化干预。
Objective: To investigate a non-invasive,smart device capable of monitoring the quantitative visual behavior of school age children, and to analyze quantitatively the relationship between visual behavior and the occurrence of myopia. Methods: This study recruited 171 subjects aged between 7 and 11 years from the third grade of Shiwan SecondPrimary School and the fifth grade of Shicheng Middle School in Chancheng District, Foshan City. Participants werecategorized into a myopia group (108 subjects) and a non-myopia group (63 subjects) based on results from non-ciliary muscle paralysis optometry. All subjects wore "clips" to track their near-work distance, near-work duration, lighting conditions during near-work, and time spent on outdoor activities between September 21, 2020, and October 10, 2020. Differences in these habits between the myopia and non-myopia groups were compared, and logistic regression analysis was conducted to assess the impact of habitual eye use on myopia. Results: The prevalence of myopia was found to be 63.2%. Statistically significant differences (all P<0.05) were observed between the myopic and non-myopic groups regarding average daily near-work time, average single near-work session duration, average near-work distance, average daytime and nighttime near-work lighting conditions, average daily outdoor activity time, and average daily effective outdoor activity exposure. Logistic regression analysis indicated that longer average single near-work sessions and increased average daily near-work time were risk factors for myopia. Spearman correlation analysis further supported these findings, showing a positive correlation between average single near-work session duration and average daily  near-work time with the occurrence of myopia (all P<0.05). The predictive accuracy of a model combining average single near-work session duration and average daily near-work time for myopia occurrence was high, with an area under the curve of 0.939. Conclusions: The wearable device "Cloud clip" effectively monitors the visual behavior of school-age children. The occurrence of myopia in this age group may be associated with increased near-work activities. A predictive model incorporating refractive development in myopic children can assess the quantitative risk of myopia, enabling the classification and management of school-age children. Personalized interventions may serve as protective factors against myopia.

Hallermann-Streiff 综合征继发青光眼:病例系列报告与文献回顾

Glaucoma in Hallermann-Streiff syndrome: case series report and literature review

:188-198
 
目的:分析Hallermann-Streiff综合征(Hallermann-Streiff syndrome,HSS)继发性青光眼的临床表现,探讨其治疗方法。方法:采用病例系列研究与文献回顾方法,记录3例确诊为HSS继发性青光眼患者的视力、眼压、裂隙灯、超声生物显微镜、相干光断层扫描、角膜地形图、A超、B超、X线眼眶大小测量等检查结果。随访患者药物治疗、周边虹膜切除术、小梁切除术或青光眼阀植入术的疗效。结果:3例患者年龄分别为9、29和47岁,其中女性2例、男性1例。最佳矫正视力为0.04-0.5,平均屈光度为+12.1D,平均眼压为37.7 mmHg,平均角膜直径为9.1 mm,平均中央前房深度为2.43 mm,平均眼轴长度为18.13 mm,角膜地形图示平均K1值为56.97 D,平均K2值为60.65 D。眼眶水平径为28.86~31.40 mm,垂直径为30.16~32.90 mm。2例年轻患者为无晶状体眼,伴葡萄膜炎、瞳孔区纤维膜、视盘旁脉络膜萎缩弧。年长患者表现为蓝色巩膜、白内障、房角关闭,眼底表现为青光眼性视杯凹陷。3例患者平均身高143 cm,伴头发及眉毛稀疏、额头前凸、鼻子呈喙状、牙齿发育不全、下颌发育不全。术后平均随访47.7个月(范围:11~84个月),眼压控制,视力与术前一致,无治疗相关并发症出现。结论:HSS继发性青光眼的眼部病变可表现为小眼眶、小眼球、小角膜、蓝色巩膜、无晶状体、瞳孔区纤维膜、葡萄膜炎、继发性青光眼及视盘旁脉络膜萎缩。对HSS继发性青光眼的患者,个性化地选择治疗方案,可以获得较好的治疗效果。
Objective: To demonstrate the clinical characteristics and surgical effects of glaucoma in Hallermann-Streiff syndrome(HSS). Methods: Observational case series and literature review. The results of ophthalmic examinations of three patients diagnosed as glaucoma with HSS were recorded, including visual acuity, intraocular pressure (IOP), slit-lamp microscopy, ultrasound biomicroscopy, optical coherence tomography, corneal topography, A-scan and B-scan ultrasonography, and orbital size measurement by X-ray. Peripheral iridectomy, glaucoma drainage device implantation or trabeculectomy, were performed in these patients. Results: Three HSS patients were 9, 29 and 47 years old, respectively, including 2 females and 1 male. The best corrected visual acuity was 0.04-0.5. The mean spherical equivalent refraction was +12.1 D. The average IOP was 37.7 mm Hg, and the average corneal diameter was 9.1 mm. The average central anterior chamber depth was 2.43mm. The average axial length was 18.13mm. Keratometry showed average K1 of 56.97 degrees, and K2 of 60.65 degrees. Two younger patients were aphakic bilaterally with uveitis, pupillary fibrous membrane and peripapillary choroidal atrophy. The older patient showed blue sclera, cataract, and anterior chamber angle closure. The horizontal orbital diameter was 28.76-31.40 mm, and vertical orbital diameter was 30.16-32.90 mm. All patients were proportionate nanism, with an average height of 143 cm. Craniofacial manifestations included dyscephalia and “bird-like” face, hypotrichosis, dental anomalies, and mandibular hypoplasia. They were followed up for an average of 47.7 months(range:11-84 months) after surgery. The IOPs were all controlled, and the visual acuities remained unchanged. No treatment-related complications occurred. Conclusions: HSS patients with glaucoma may present as small orbit, microphthalmia, microcornea, blue sclera, aphakia, pupillary fibrous membrane, uveitis, with atrophic chorioretinal changes. For these patients, personalized treatment may help to achieve better therapeutic effects.

近 20 年热休克蛋白在眼科中的研究进展及趋势:文献计量学研究

Advances and trends of heat shock proteins in ophthalmology in the past 20 years

:199-209
 
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。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(=394)是发文量最多的国家,Investigative Ophthalmology & Visual Science(=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 (=394) was the leading contributor among countries. Investigative Ophthalmology & Visual Science (=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.
综述

碳点的特性及其在眼科疾病诊治中的研究进展

Research progress in the application of carbon dots in the diagnosis and treatment of ocular diseases

:210-219
 
碳点是一种新型荧光碳纳米材料,直径一般小于10 nm,具有自发荧光、高生物组织相容性、易于修饰、成本低廉等优点,在生物医学领域拥有广阔的应用前景。眼球因其独特的屏障结构,常规药物停留时间短、穿透性差,通过局部滴眼到达病灶的药物浓度有限,需要增加给药频次以保持药效。另外,糖尿病性黄斑水肿(diabetic macular edema,DME)、脉络膜新生血管(diabetic macular edema,CNV)等疾病的治疗给药则需依赖于玻璃体腔注射,该方法属于有创操作,有引起潜在并发症的可能,且需多次注射,给患者造成了沉重的心理和经济负担。优化眼部给药方法一直是眼科学领域的研究热点。基于碳点的优异特性,碳点在眼部药物递送、眼部成像、眼疾病诊疗中已展现出优秀的应用潜力。本综述将综合介绍碳点的特点及近十年来碳点在眼科疾病诊疗中的研究进展,旨在提供关于碳点在眼科应用现状的系统性认识,为未来研究提供方向。
Carbon dots is a new type of fluorescent carbon nanomaterial, which the diameter is generally less than 10 nm, has the advantages of self-fluorescence, remarkable biocompatibility, easy modification, low cost and so on, has a broad application prospect in the biomedical field. Due to the unique barrier of the eye, conventional drugs have a short residence time and poor penetration, so the concentration of drugs that can reach the lesions through local eye drops is limited, and for what to increase the frequency of administration to maintain efficacy. Up to now, the treatment of posterior eye diseases, such as diabetic macular edema (DME), choroidal neovascularization (CNV) and other diseases still rely on repeated vitreous injection, which is an invasive procedure with potential complications, and need multiple injections, causing a heavy psychological and economic burden on patients. Optimizing the method of ocular drug delivery has always been a hot topic in the field of ophthalmology. Carbon dots have shown excellent application potential in the ocular drug delivery, ocular imaging, and diagnosis and treatment of ocular disease based on its excellent characteristics. This review will systematically introduce the characteristics of carbon dots and the application of carbon dots in the diagnosis and treatment of eye diseases, aiming to provide a comprehensive understanding of the current situation of the application of carbon dots in ophthalmology and provide directions for future research.

糖基化蛋白修饰在眼部疾病的研究进展

Research progress on protein glycosylation modification in ocular diseases

:220-228
 
糖基化是一种重要的蛋白质翻译后修饰,通常发生在内质网和高尔基体的特定位置。N-糖基化和O-糖基化是最常见的糖基化修饰类型。与其他翻译后修饰相比,糖基化具有独特的生物学意义,包括结构的复杂多样性,生物功能的重要性以及进化上的保守性。糖基化修饰对于蛋白质稳定性、细胞黏附与识别、细胞内信号传导和表观遗传学具有重要影响,从而参与调节细胞生物学和发病机制。近年来,越来越多的研究揭示了糖基化参与眼部疾病的发生和发展,包括眼表疾病、圆锥角膜、青光眼、年龄相关性黄斑变性、视网膜色素变性、糖尿病视网膜病变等。眼部蛋白糖基化异常可通过诱发新生血管形成、炎症反应、氧化应激、异常免疫应答等改变细胞的结构与功能,进而影响各种眼病的发生发展。通过深入研究糖基化在不同眼部疾病中的作用机制,可以为相关眼部疾病的早期诊断和治疗提供新的思路和方法。现综述糖基化在眼部疾病的研究进展,以探究调控蛋白质糖基化对眼部疾病的诊疗意义。
Glycosylation is an important post-translational modification of proteins that usually occurs at specific locations within the endoplasmic reticulum and Golgi apparatus. N-glycosylation and O-glycosylation are the most common types of glycosylation modifications. Compared to other post-translational modifications, glycosylation has unique biological significance, including structural complexity and diversity, crucial biological functions, and evolutionary conservation. Glycosylation modifications significantly impact protein stability, cell adhesion and recognition, intracellular signal transduction, and epigenetics, thereby regulating cellular biology and pathogenesis. In recent years, an increasing amount of research has revealed the involvement of glycosylation in the occurrence and development of ocular diseases, including ocular surface diseases, keratoconus, glaucoma, age-related macular degeneration, retinitis pigmentosa, and diabetic retinopathy. Abnormal glycosylation of ocular proteins can induce changes in cell structure and function through mechanisms such as neovascularization, inflammatory response, oxidative stress, and abnormal immune response, thereby influencing the occurrence and development of various eye diseases. By deeply studying the mechanisms of glycosylation in different ocular diseases, new insights and methods can be provided for the early diagnosis and treatment of related ocular diseases. This review summarizes the research progress of glycosylation in ocular diseases to explore the diagnostic and therapeutic significance of regulating protein glycosylation in ocular diseases.
封面简介

双模态全视场光学相干层析技术的角膜缘高分辨率成像

High-resolution imaging of limbus tissue with dual-mode full-field optical coherence tomography

:03-03
 
角膜缘的细胞,特别是角膜缘干细胞,对于维持角膜的透明和健康至关重要。基于影像技术对角膜缘进行高精度可视化评价是相关疾病诊疗的重要手段。眼科临床使用的裂隙灯显微镜、共聚焦显微镜、眼前节光学相干断层扫描仪(optical coherence tomography,OCT)等成像技术,因低分辨、低对比度、侵入性等原因,限制了其在角膜缘细胞结构及功能影像评估中的应用。本团队创新研发新型双模态全视场光学相干断层扫描仪(full-field OCT,FFOCT),成功实现了无标记的角膜缘细胞级分辨率结构及功能成像。FFOCT基于空间非相干光平面干涉原理提取组织内部散射光,获得微米级分辨率三维结构成像;通过FFOCT原始相干信号的高时空分辨率采集及动态特征解析,实现源于活细胞新陈代谢运动的无标记细胞功能影像可视化。双模态FFOCT创新性地整合了高分辨率、无标记的结构及功能成像模态,不仅清晰获取角膜缘组织的高精结构特征如Vogt栅栏、角膜缘隐窝、血管壁等,同时还能捕捉不同角膜缘细胞内的代谢活性动态变化,无需使用外源荧光染料或标记剂,为角膜缘生物学及疾病机制研究提供全新细胞水平结构及功能成像方法,具有广泛应用前景。
角膜缘的细胞,特别是角膜缘干细胞,对于维持角膜的透明和健康至关重要。基于影像技术对角膜缘进行高精度可视化评价是相关疾病诊疗的重要手段。眼科临床使用的裂隙灯显微镜、共聚焦显微镜、眼前节光学相干断层扫描仪(optical coherence tomography,OCT)等成像技术,因低分辨、低对比度、侵入性等原因,限制了其在角膜缘细胞结构及功能影像评估中的应用。本团队创新研发新型双模态全视场光学相干断层扫描仪(full-field OCT,FFOCT),成功实现了无标记的角膜缘细胞级分辨率结构及功能成像。FFOCT基于空间非相干光平面干涉原理提取组织内部散射光,获得微米级分辨率三维结构成像;通过FFOCT原始相干信号的高时空分辨率采集及动态特征解析,实现源于活细胞新陈代谢运动的无标记细胞功能影像可视化。双模态FFOCT创新性地整合了高分辨率、无标记的结构及功能成像模态,不仅清晰获取角膜缘组织的高精结构特征如Vogt栅栏、角膜缘隐窝、血管壁等,同时还能捕捉不同角膜缘细胞内的代谢活性动态变化,无需使用外源荧光染料或标记剂,为角膜缘生物学及疾病机制研究提供全新细胞水平结构及功能成像方法,具有广泛应用前景。
其他期刊
  • 眼科学报

    主管:中华人民共和国教育部
    主办:中山大学
    承办:中山大学中山眼科中心
    主编:林浩添
    主管:中华人民共和国教育部
    主办:中山大学
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  • Eye Science

    主管:中华人民共和国教育部
    主办:中山大学
    承办:中山大学中山眼科中心
    主编:林浩添
    主管:中华人民共和国教育部
    主办:中山大学
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