视网膜微循环与脑小血管具有相似的特征。视网膜被认为是可检测到的“窗口”，以检测在神经退行性疾病中发生的微血管损伤。光学相干断层扫描血管造影(optical coherence tomography angiography，OCTA)是一种非侵入性成像方式，可提供视网膜、脉络膜和视神经中血流的深度分辨图像。现总结有关OCTA在与眼科相关的阿尔茨海默病、帕金森病、多发性硬化症及视神经退行性疾病等神经系统疾病中的应用，并讨论其可否作为早期诊断和监测神经退行性疾病的重要工具。
Retinal microcirculation shares similar features with cerebral small blood vessels. Thus, the retina may be considered as an accessible ‘window’ to detect the microvascular damage occurred during the development and progression of neurodegenerative disorders. Optical coherence tomography angiography (OCTA) is a non-invasive imaging modality providing in-depth and high-resolved images of blood flow in the retina, choroid,and optic nerve. In this review, we summarize the current advances in the application of OCT-A in neurological diseases associated with ophthalmology such as Alzheimer’s disease, Parkinson’s disease, multiple sclerosis and optic nerve degenerative diseases. Future directions for evaluating whether OCTA can be used as an important tool to early diagnose and monitor the neurodegenerative disorders are also discussed.
光学相干断层扫描血管成像(optical coherence tomography angiography，OCTA)是一种非接触、无创的、快速的血管造影技术，它通过检测红细胞在血管内的光学相干断层扫描(optical coherence tomography，OCT)信号的变化来提供血管影像。由于这项技术不需要注射血管造影剂，使得它比传统的眼科血管造影技术更安全。在前节疾病的检查中，OCTA不仅能够量化前节血管的范围和密度，还显示出良好的成像质量，为临床监测疾病的病程和对治疗的反应提供客观的评价。
Optical coherence tomography angiography (OCTA) is a noncontact, noninvasive, and rapid angiography technique. It provides vascular images by detecting changes in the optical coherence tomography (OCT) signal of red blood cells in the blood vessel. Since this technique does not require injection of angiography, it is safer than traditional ophthalmic angiography. In the examination of anterior segment diseases, OCTA can not only quantify the range and density of anterior segment blood vessels, but also shows good imaging quality, providing an objective evaluation for clinical monitoring of the disease course and response to treatment.
光学相干断层扫描血管成像术(optical coherence tomography angiography，OCTA)作为一项新兴的检查手段，现已被广泛应用于眼科临床及科研工作中。鉴于OCTA在血管成像方面的独特优势，近年来关于其在眼前段的临床应用和研究也愈发得到关注。关于OCTA对结膜、巩膜、角膜以及虹膜的血管和相关眼表疾病的研究日益增多，其在眼前段应用潜力巨大。
As a new examination method, optical coherence tomography angiography (OCTA) has been increasingly used in ophthalmology clinical work and scientific research. In view of the unique advantages of OCTA in angiography,the clinical application and research of OCTA in the anterior segment have attracted more and more attention in recent years. Studies of OCTA in vessels of conjunctiva, sclera, cornea, iris, and related ocular surface diseases have shown great potential for its application in the anterior segment.
目的：应用Cirrus HD-OCT 5000对正常眼黄斑及视盘血流参数进行血管成像测量，评估其可重复性及再现性。方法：纳入40只正常眼进行前瞻性研究。操作者A于一周内3天的同一时段(T1，T2，T3)对正常受试者的同一眼黄斑及视盘进行3次血管成像扫描，扫描过程中均开启FastTracTM图像跟踪功能，操作者B在T 2时间点再次对受试者同一眼进行相同程序扫描，使用Angio PlexMetrixTM量化软件(版本10.0)自动测量黄斑和视盘的血管长度密度(vessel length density，VD)和血管灌注密度(vascular perfusion density，PD)。应用单因素方差分析或非参数检验比较3次扫描的VD、PD是否有差异。采用组内相关系数(intraclass correlation coefficient，ICC)、变异系数(coefficient of variation，CV)评价操作者A的可重复性，采用一致性相关系数(consistent correlation coefficient，CCC)、重复性系数(repeatability coefficient，CR)、C V评价操作者间的再现性。结果：操作者A对黄斑及视盘各区域3次扫描的V D、P D之间差异无统计学意义(P >0.05)。操作者A对黄斑和视盘V D、PD 3次扫描的ICC值分别为0.260~0.517、0.362~0.898，黄斑及视盘各区域V D、P D的C V值均<8.1%。黄斑和视盘V D、P D的操作者间CCC值分别为0.3130~0.5665、0.5149~0.7801；黄斑VD和PD的CR值分别为3.2212~4.6399、0.0574~0.0832；视盘VD和PD的CR值分别为2.0675~4.0630、0.0447~0.0730。黄斑CV值均<9.0%，视盘CV值均<6.9%。结论：非同日的同一时段视盘浅层血流参数具有较好的重复性及再现性，黄斑浅层血流参数的重复性及再现性相对较差。
Objective: To evaluate the repeatability and reproducibility of quantification of macular and peri-papillary superficial capillaries in normal eyes using Cirrus HD-OCT 5000 angiography. Methods: Forty normal eyes were included in this prospective study. Angiography 3 mm × 3 mm scan protocol centered on the disc or macula of the same eye was repeated 3 times by operator A in the same period on 3 days (T1, T2, T3) within 1 week,and the FastTracTM image tracking function was turned on during the scan. Operator B repeated the same scan independently at T2 after operator A. Angio Plex MetrixTM quantification software (version 10.0) was used to automatically measure the vessel length density (VD) and vascular perfusion density (PD) of macular and peri-papillary superficial capillaries. One-way analysis of variance or nonparametric test was used to compare the VD and PD measurements of the 3 scans. The intraclass correlation coefficient (ICC) and coefficient of variation (CV)were calculated to evaluate the intra-operator repeatability. Consistent correlation coefficient (CCC), repeatability coefficient (CR), and CV were calculated to evaluate the inter-operator reproducibility. Results: There was no statistically significant difference in the measurements of VD and PD between the 3 scans of the macular and peri-papillary superficial capillaries by operator A (P>0.05). The ICC values for the 3 scans of VD and PD of the macular and peri-papillary superficial capillaries by operator A were 0.260–0.517 and 0.362~0.898, respectively.The CV values of the VD and PD of the macular and peri-papillary superficial capillaries were all <8.1%. The inter-operator CCC values of the macular and peri-papillary superficial capillaries were 0.3130–0.5665 and 0.5149~0.7801,respectively; the CR values of the VD and PD of macula were 3.2212–4.6399 and 0.0574–0.0832, respectively; the CR values of the VD and PD of optic disc were 2.0675–4.0630 and 0.0447–0.0730, respectively. The CV values of macular were all <9.0%, and the CV values of optic disc were all <6.9%. Conclusion:The macular and peri-papillary superficial capillaries parameters in the same period on different days have a good repeatability and reproducibility,while the superficial macular blood flow parameters have relatively poor repeatability and reproducibility.
目的：探讨光学相干断层扫描血管成像(optical coherence tomography angiography，OCTA)扫描信号强度对视盘周围血管密度的影响。方法：本研究为单中心横断面研究，所有受试者分别接受了身高、体重、血压、眼压、眼轴及视盘OCTA检查，利用广义估计方程分析OCTA扫描信号强度对视盘周围血管密度的影响。结果：共186人359眼纳入本研究，年龄为(47.86±17.86)岁，视盘周围血管密度为(17.75±1.99)mm?1 。单因素分析显示视盘周围血管密度与眼轴呈负相关(β=?0.5120，P<0.001)，与扫描信号强度呈正相关(β=1.0240，P<0.001)。在校正了年龄、性别、视盘面积及眼轴后的多因素分析中，OCTA扫描信号强度依然与视盘周围血管密度显著正相关(β=0.9721，P<0.001)。结论：视盘周围血管密度不仅与眼轴和视盘面积显著负相关，而且与OCTA扫描信号强度显著正相关，在临床应用或研究中，需要考虑其影响。
Objective: To explore the effect of scanning signal intensity on the peripapillary vessel density measured by optical coherence tomography angiography (OCTA). Methods: This study was a single-center cross-sectional study. All the participants received comprehensive examinations including height, weight, blood pressure,intraocular pressure, axial length, and OCTA scan of the optic disc. The effect of OCTA scanning signal intensity on the peripapillary vessel density was analyzed using the generalized estimation equation. Results: A total of 186 participants with 359 eyes were included in this study. The mean age of all the participants was (47.86±17.86)years old, and the average peripapillary vessel density was (17.75±1.99)mm?1. In a univariate analysis,peripapillary vessel density was associated with the axial length (β=?0.5120, P<0.001) and the scanning signal intensity (β=1.0240, P<0.001). After adjusting for age, gender, axial length, and optic disc area in the multivariate analysis, the OCTA scanning signal intensity was still significantly associated with the peripapillary vessel density (β=0.9721, P<0.001). Conclusion: The peripapillary vessel density is significantly negatively associated with the axial length and optic disc area, significantly positively associated with the scanning signal intensity. In clinical practice, the influence needs to be considered.
目的：探究特发性黄斑前膜(idiopathic macular epiretinal membrane，IMEM)患者在光学相干断层扫描(optical coherence tomography，OCT)的形态学改变与视力的相关性。方法：回顾性研究。基于OCT图像4级分级方案，纳入3级及以下的特发性黄斑前膜患者35例共37只眼进行OCT扫描，并借助第三方软件分析并获取每只眼在黄斑中心凹直径分别为1、3、6 mm共3个同心圆区域内视网膜各层的平均厚度值，并按照是否存在内核层(inner nuclear layer，INL)囊样改变分为两组。通过建立最小分辨角对数(minimum resolution angle in logarithmic，logMAR)最佳矫正视力(best corrected vision acuity，BCVA)与视网膜各层厚度值的多元线性回归方程，以及比较有INL囊样改变及无INL囊样改变两组的视力，分析视力与视网膜各层厚度值及INL囊样改变的关系。结果：多元线性回归分析显示，在直径1 mm的区域内，logMAR BCVA与神经纤维层(retina nerve fiber layer，RNFL)、INL的厚度值均呈正相关(均P<0.05)，而在直径3 mm和6 mm的区域内，logMAR BCVA仅与INL的厚度值呈正相关(均P<0.05)。与无INL囊样改变组相比，有INL囊样改变组视力及INL厚度差异均有统计学意义(均P<0.05)。结论：特发性黄斑前膜患者当前的视力主要与RNFL和INL厚度值相关。发生在INL层的囊样改变可能很好的提示INL增厚，其与视力具有相关性，具有这种囊样改变的患者往往视力也较差。
Objective: To investigate the morphological changes detected by spectral domain optical coherence tomography (OCT) and their relevance to vision in patients with idiopathic macular epiretinal membranes (IMEM). Methods: This is a retrospective study. OCT recorded 37 eyes with stage 3 and below IMEM according to the 4-level grading system based on OCT images among 35 patients. We managed to obtain thickness of all retina layers in three concentric circular regions with a diameter of 1 mm, 3 mm and 6 mm across macular fovea with the help of a third-party software. Plus we divided all 37 eyes into two groups according to whether there were cystic changes in the inner nuclear layer (INL). Multiple linear regression analyses were performed between thickness of all retina layers and current minimum resolution angle in logarithmic (logMAR) best corrected visual acuity (BCVA). The difference of BCVA between groups with cystic changes and without was also compared. Thus, the relationships between visual acuity and thickness of retina layers, cystic changes in INL were analyzed. Results: Multiple linear regression analyses revealed that thickness of both retina nerve fiber layer (RNFL) and inner nuclear layer have positive correlation with logMAR BCVA in the region with a diameter of 1 mm (P<0.05), while in regions of a diameter of 3 mm and 6 mm, only INL thickness remained positively relevant (all P<0.05). There were significant differences in BCVA and thickness of INL between groups with INL cystic changes and without (all P<0.05). Conclusion: Current visual acuity among preoperative IMEM patients was mostly associated with thickness of RNFL and INL. Cystic change in INL layer may be a good indicator of INL thickening and was visually correlated. Those with this change tend to have worse vision.
目的：观察急性中心性浆液性脉络膜视网膜病变(central serous chorioretinopathy，CSC)的自然病程中渗漏点的形态及变化。方法：本研究为前瞻性研究，使用光学相干断层扫描(optical coherence tomography，OCT)观察从发病到发病后5~13个月的CSC患者的渗漏点的OCT形态，测量并计算Hall层、脉络膜全层各自厚度及比值，并进行比较。结果：共20例患者[男14例，女6例，年龄33~59(中位数41)岁]纳入研究。随访时间为5~13个月。在19例患者中观察到微小视网膜色素上皮脱离(pigment epithelium detachment，PED)。1例患者可见视网膜色素上皮(retinal pigment epithelium， RPE)小凸起。在随访期间，仅1例患者的PED完全恢复，其他19例患者在视网膜下液被完全吸收时，RPE和Bruch膜之间仍存在微小分离。渗漏点处的Haller层/脉络膜厚度显著高于中央凹处(初诊时0.806±0.08 vs 0.863±0.06，P=0.003；最后1次随访时为0.801±0.07 vs 0.851±0.06，P=0.004)。结论：本研究观察到在急性CSC患者自然病程中，即使视网膜下液吸收，OCT显示渗漏点处仍存在持续的PED，更厚的Haller层及更薄的内层脉络膜，这些发现为CSC的发病机制提供了更多线索。
Objective: To observe the morphology and changes of leakage points in the natural course of acute central serous chorioretinopathy (CSC). Methods: This study was a prospective study, using optical coherence tomography to observe the OCT morphology of leakage points in CSC patients from onset to 5 to 13 months after onset, measuring the thickness and ratio of Hall layer and the whole choroid, and then compare them. Results: A total of 20 patients were included in the study, including 14 males and 6 females, aged from 33 to 59, with the median being 41 years old. The follow-up time ranged from 5 months to 13 months. Minute retinal pigment epithelial detachments (PED) were observed in 19 patients. A small bulge of retinal pigment epithelium (RPE) was observed in 1 patient. During the follow-up, only one patient totally recovered. Small separation between RPE and Bruch membrane still exit even subretinal fluid were absorbed completely in the other 19 patients. The thickness of Haller layer or choroid at the leakage point was significantly higher than that of the fovea (0.806±0.08 vs 0.863±0.06, P=0.003, at the first visit; 0.801±0.07 vs 0.851±0.06, P=0.004, at the last follow-up). Conclusion: This study observed that in the natural course of acute CSC patients, even if the subretinal fluid was absorbed, OCT still showed that there was persistent PED at the leakage point, thicker Haller layer and thinner inner choroid layer. These findings provided more clues to the pathogenesis of CSC.
目的：针对活体共聚焦显微镜(in vivo confocal microscopy，IVCM)和传统光学相干层析技术(optical coherence tomography，OCT)在人眼角膜成像各自存在成像视野小或无法细胞成像的限制，开发具有高分辨率的非接触全视场光学相干层析系统(full-field optical coherence tomography，FFOCT)，实现活体人眼角膜细胞结构FFOCT成像。方法：FFOCT系统采用高数值孔径干燥显微物镜及高速面阵相机，使用双相位调制图像处理方法，实现系统高速高分辨率非接触成像。利用系统对健康人眼进行角膜各深度层的活体FFOCT成像验证其可行性。结果：本研究团队研发了FFOCT的新型活体人眼角膜高分辨率成像系统，实现理论平面成像分辨率1.7 μm，成像视野1.26 mm×1.26 mm，成像速率达275帧/s。利用该系统对正常活体人眼角膜成像实验，在非接触情况下获取了角膜各主要结构层的高分辨率结构影像。结论：FFOCT高分辨率活体人眼角膜成像系统兼具了传统OCT的非接触、大成像视野及IVCM的细胞级别平面分辨率的优势，将为角膜疾病的研究及临床诊疗提供全新的成像分析技术。
Objective: Due to the limitations of small imaging field of view of in vivo confocal microscopy (IVCM) or the incapability of cellular imaging of traditional optical coherence tomography (OCT) in human corneal imaging, this study was designed to develop a novel high-resolution in vivo human corneal imaging system based on full-field OCT (FFOCT). Methods: The FFOCT system utilized a high numerical aperture air immersion microscope objective and a high-speed area array CMOS camera with two-phase modulation image processing algorithm to achieve high-speed high-resolution non-contact imaging of human cornea. To verify its feasibility, in vivo cornea imaging at different depth was performed on a healthy human subject. Results: The FFOCT system achieved a theoretical lateral imaging resolution of 1.7 μm, an imaging field of view of 1.26 mm×1.26 mm, and an imaging rate of 275 Hz/s. High-resolution FFOCT images of the main structural layers of cornea were achieved by imaging a healthy human cornea in vivo with this system in a non-contact way. Conclusion: The FFOCT human corneal imaging system combines the advantages of the non-contractness and the large imaging field of view of traditional OCT with the cellular lateral resolution of IVCM, potentially providing a new imaging system for the research and clinical diagnosis and treatment of corneal diseases.
目的：探讨光学相干断层扫描血管成像(optical coherence tomography angiography，OCTA)在糖尿病性视网膜病变中的应用。方法：选取2021年中山大学附属第七医院眼科63例糖尿病患者为研究对象，分为无糖尿病性视网膜病变(T0，21眼)、轻度非增殖期(T1，21眼)、中重度非增殖期(T2，14眼)及增殖期(T3，7眼)。收集各组生化指标，包括空腹血糖、糖化血红蛋白、谷丙转氨酶、谷草转氨酶、碱性磷酸酶、血清尿素氮、肌酐、尿素氮肌酐比值，及OCTA数据，即中心视网膜厚度、Angiography3×3及Angiography6×6血管线性密度及血管灌注密度等。采用单因素方差分析比较各组间差异。结果：T2组、T3组与T0组相比，T3组与T1组相比，糖尿病病程延长；T3组与其他各组相比，尿素氮升高；T1组、T2组、T3组与T0组相比，T3组与T1组相比，6 mm ×6 mm外层血流线性密度减少；与T0组相比，T1组、T2组及T3组6 mm ×6 mm完整血流线性密度减少；与T0相比，T2组、T3组6 mm ×6 mm外层血流灌注密度减少；与T0组相比，T3组6 mm ×6 mm完整血流灌注密度减少；T2组、T3组与T0组相比，T3与T1相比，3 mm ×3 mm内层血流线性密度明显减少；T3组与T0组及T1组相比，3 mm ×3 mm完整血流线性密度减少。结论：随着糖尿病性视网膜病变的进展，患者的尿素氮及肌酐逐渐升高，OCTA的血流线性密度及血流灌注密度逐渐减少。与血流灌注密度相比，血流线性密度对于早期糖尿病性视网膜病变筛查可能更为敏感。而利用Angiography6×6模式可能可以更早地发现糖尿病性视网膜病变的视网膜血流变化。
Objective: To explore the applications of optical coherence tomography angiography (OCTA) in diabetic retinopathy. Methods: A total of 63 diabetic patients in the Department of Ophthalmology, Seventh Affiliated Hospital of Sun Yat-sen University in 2021 were divided into 4 groups: the patients without diabetic retinopathy (T0, n=21), mild non-proliferative diabetic retinopathy (T1, n=21), moderate-to-severe non-proliferative diabetic retinopathy (T2, n=14) and proliferative diabetic retinopathy (T3, n=7). Biochemical Indicators were collected in all patients, such as fasting plasma glucose (FPG), glycated hemoglobin A1c (HbA1c), alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), the blood urea nitrogen (BUN), creatinine (CRE) and the ratio of blood urea nitrogen and creatinine (BUN/CRE). The Macular Cube 521×128, Angiography3×3, and Angiography6×6 models of OCTA were used to obtain central retinal thickness (CRT), vascular density (VD) and perfusion density (PD) of each group. The data of all subjects was applied to do one-way ANOVA. Results: Prolonged duration of diabetes in T2 and T3 compared to T0 and in T3 compared to T1. Elevated BUN in T3 compared to all other groups. When T1, T2 and T3 were compared to T0, and T3 was compared to T1, the VD of the 6 mm ×6 mm outer layer decreased. Reduced VD of intact 6 mm ×6 mm region in T1, T2 and T3 compared to T0. Declining PD of the 6 mm ×6 mm outer layer in T2 and T3 compared to T0. Diminished PD of whole 6 mm ×6 mm area at T3 compared to T0. The VD of 3 mm ×3 mm inner layer was significantly reduced in T3 compared to T0 and T1. The VD of 3 mm ×3 mm intact area gradually dwindled in T3 compared with T0 and T1 (P<0.05). Conclusion: With the progression of diabetic retinopathy, the levels of BUN and CRE gradually increased, and the OCTA-derived vascular density and perfusion density gradually decrease. Vascular density may be more sensitive for early diabetic retinopathy screening than perfusion density.The use of the Angiography6×6 model may result in an earlier detection of changes in retinal blood flow in diabetic retinopathy.
目的：探讨光学相干断层扫描血管成像技术(optical coherence tomography angiography，OCTA)在斜视性弱视伴偏中心注视患者中应用的价值。方法：收集2018年1月到2020年5月斜视性弱视伴偏中心注视的患者17人为研究组，采用OCTA系统软件工具，以μm为单位测量视网膜固视点和黄斑中心凹之间的距离，同时收集非斜视、弱视且中心注视健康者17人为对照组，并分析受试者的浅层视网膜血管丛的黄斑中心凹血流长度密度(vessel length density，VLD)、灌注密度(perfusion density，PD)、黄斑中心凹无血流信号区(foveal avascular zone，FAZ)、面积、FAZ周长及FAZ圆形度。结果：斜视组弱视眼偏心距离为(632.18±310.62) μm，黄斑中心凹浅层血管丛VLD为(5.31±3.44) mm?1，PD为0.16±0.08，黄斑中心凹无血流信号区FAZ面积(0.28±0.17) mm2，FAZ周长(2.05±0.56) mm、FAZ圆形度0.67±0.06；与研究组対侧眼和对照组相比，VLD差异有统计学意义(P<0.05)，PD、FAZ面积等差异无统计学意义(P>0.05)。斜视组弱视眼偏心度与偏中心距离显著相关(r=0.834，P<0.001)。结论：OCTA可以量化偏中心距离，斜视性弱视伴偏中心注视眼的黄斑中心凹血流长度密度较対侧眼及健康眼低。
Objective: To explore the application value of optical coherence tomography angiography (OCTA) in patients with strabismic amblyopia accompanied by eccentric fixation. Methods: Seventeen strabismus amblyopia patients with eccentric fixation admitted to our hospital from January 2018 to May 2020 were enrolled as the study group. OCTA software was used to measure the distance between fixation point and macular fovea in micron units. Seventeen non-strabismus and non-amblyopia patients with centric fixation were enrolled as the control group. Vessel length density (VLD), perfusion density (PD), and foveal avascular zone (FOZ) were measured for the superficial retinal vascular cluster. Perimeter of FAZ and circularity of FAZ were analyzed. Results: The eccentric fixation distance was (632.18 ±310.6) μm, the macular fovea retinal thickness was (207.82±17.79) μm, the VLD of the superficial retinal vascular plexus was (5.31±3.44) mm?1, the PD was 0.16±0.08, the FAZ area was 0.28±0.17 mm2, the FAZ perimeter was 2.05±0.56 mm, and the FAZ circularity was 0.67±0.06. These results showed statistically significant differences in the VLD compared with the fellow eyes (P=0.043) and the control group (P=0.049), but there were no statistically significant differences in the PD, or FAZ area. In the strabismus group, the eccentricity of amblyopia was significantly correlated with the eccentric distance (r=0.834, P<0.001). Conclusion: OCTA can quantify the eccentric distance. The blood flow length density of macular fovea in strabismic amblyopia with eccentric fixation is lower than that in contralateral and healthy eyes.
