1 华中科技大学武汉光电国家研究中心，高端生物医学成像重大科技基础设施，生物医学光子学教育部重点实验室，Britton Chance生物医学光子学研究中心，湖北 武汉 430074
2 天津市眼科医院，南开大学附属眼科医院，天津医科大学眼科临床学院，南开大学眼科学研究院，天津 300020
飞秒激光得益于其精准、微创等优势被广泛应用于屈光疾病的治疗。在飞秒激光屈光手术中，光学系统的数值孔径是影响手术效果的重要参数。本研究旨在探讨数值孔径对飞秒激光角膜基质切削质量的影响规律，以帮助临床医生更好地选择合适的手术参数。选用0.16、0.30、0.80三种数值孔径进行离体动物角膜的飞秒激光切削实验，并通过气泡尺寸与凋亡细胞比例评估激光切削质量与基质细胞损伤程度。实验结果显示：气泡体积随着数值孔径的增大而减小，高数值孔径下切割更易实现基质层的分离；上述三种数值孔径下的基质细胞损伤比例分别为9.4%、4.9%和1.0%，基质细胞的损伤比例随着数值孔径的增大而明显下降。因此，增大数值孔径有助于提高飞秒激光角膜基质切削的安全性。
激光技术 飞秒激光 角膜 数值孔径 气泡 细胞损伤
Author Affiliations
Abstract
1 Research and Development, SCHWIND Eye-Tech-Solutions, 63801 Kleinostheim, Germany
2 Interdisciplinary Center for Scientific Computing (IWR), Universität Heidelberg, 69117 Heidelberg, Germany
3 Mannheim Institute for Intelligent Systems in Medicine (MIISM), Universität Heidelberg, 69117 Heidelberg, Germany
4 Central Institute for Computer Engineering (ZITI), Universität Heidelberg, 69117 Heidelberg, Germany
5 CZS Heidelberg Center for Model-Based AI, Universität Heidelberg, 69117 Heidelberg, Germany
Purpose: Despite theoretical models for achieving laser-based ablation smoothness, methods do not yet exist for assessing the impact of residual roughness after corneal ablation, on retinal polychromatic vision. We developed a method and performed an exploratory study to qualitatively and quantitatively analyze the impact of varying degree of corneal roughness simulated through white and filtered noise, on the retinal image. Methods: A preliminary version of the Indiana Retinal Image Simulator (IRIS) [Jaskulski M., Thibos L., Bradley A., Kollbaum P., et al. (2019) IRIS – Indiana Retinal Image Simulator. https://blogs.iu.edu/corl/iris] was used to simulate the polychromatic retinal image. Using patient-specific Zernike coefficients and pupil diameter, the impact of different levels of chromatic aberrations was calculated. Corneal roughness was modeled via both random and filtered noise [(2013) Biomed. Opt. Express4, 220–229], using distinct pre-calculated higher order Zernike coefficient terms. The outcome measures for the simulation were simulated retinal image, Strehl Ratio and Visual Strehl Ratio computed in frequency domain (VSOTF). The impact of varying degree of roughness (with and without refractive error), spatial frequency of the roughness, and pupil dilation was analyzed on these outcome measures. Standard simulation settings were pupil size = 6 mm, Defocus Z[2, 0] = 2 μm (−1.54D), and Spherical Aberrations Z[4, 0] = 0.15 μm. The signal included the 2–4th Zernike orders, while noise used 7–8th Zernike orders. Noise was scaled to predetermined RMS values. All the terms in 5th and 6th Zernike order were set to 0, to avoid overlapping of signal and noise. Results: In case of a constant roughness term, reducing the pupil size resulted in improved outcome measures and simulated retinal image (Strehl = 0.005 for pupil size = 6 mm to Strehl = 0.06 for pupil size = 3 mm). The calculated image quality metrics deteriorated dramatically with increasing roughness (Strehl = 0. 3 for no noise; Strehl = 0.03 for random noise of 0.25 μm at 6 mm diameter; Strehl = 0.005 for random noise of 0.65 μm at 6 mm diameter). Clear distinction was observed in outcome measures for corneal roughness simulated as random noise compared to filtered noise, further influenced by the spatial frequency of filtered noise. Conclusion: The proposed method enables quantifying the impact of residual roughness in corneal ablation processes at relatively low cost. Since normally laser ablation is an integral process divided on a defined grid, the impact of spatially characterized noise represents a more realistic simulation condition. This method can help comparing different refractive laser platforms in terms of their associated roughness in ablation, indirectly improving the quality of results after Laser vision correction surgery.
Residual roughness Cornea ablation Random and filtered noise Polychromatic vision Ablation smoothness Journal of the European Optical Society-Rapid Publications
2023, 19(1): 2023013
1 安徽医科大学基础医学院, 合肥 230032
2 军事科学院军事医学研究院辐射医学研究所, 北京 100039
为观察3.74 μm远红外激光致角膜损伤的特点和损伤修复过程, 利用该激光在光斑直径为2 mm、照射时间为0.8 s、辐照量为23.2 J/cm2的条件下照射C57BL/6J小鼠角膜, 采用大体观察、裂隙灯显微镜、光学相干断层扫描(OCT)以及组织病理方法, 在角膜损伤后3 h、6 h、12 h、1 d、3 d、7 d、14 d和21 d进行观察。大体观察角膜损伤即刻可见灰白色损伤斑, 表面凹凸不平, 角膜混浊随时间逐渐加重, 1 d达到顶峰, 3～7 d混浊减轻, 14～21 d再次加重。裂隙灯下角膜损伤累及全层, 角膜厚度随时间先增大后逐渐恢复。OCT观察角膜损伤后明显外凸, 反射光带全层性增强, 3 h角膜显著增厚, 12 h达到最厚, 后逐渐恢复至正常。经组织切片观察: 上皮层损伤后3 h核固缩深染, 6～12 h核染色变淡消失, 1 d 时1～2层新生上皮完全覆盖损伤区, 3～7 d上皮细胞增至3～4 层, 14～21?d恢复正常; 基质层损伤后3～6 h核染色质大量脱失, 12 h出现浸润细胞, 后浸润细胞增多, 由基质深层向浅层迁移, 14～21 d浸润细胞减少, 纤维排列仍不规则; 内皮层损伤后3 h细胞脱落, 1 d出现少量新生细胞, 其后逐渐增多并趋向恢复。结果表明, 3.74 μm激光在23.2 J/cm2照射剂量下可致角膜全层损伤, 角膜损伤反应随时间先加重后逐渐恢复, 21 d时上皮和内皮层基本恢复正常, 但基质层并未恢复透明。本研究为红外激光角膜损伤危害评价和损伤治疗研究提供了试验依据。
3.74 μm激光 照射剂量 小鼠 角膜 损伤修复 3.74 μm laser radiation dose mice cornea wound healing
1 桂林电子科技大学电子工程与自动化学院, 广西 桂林 541004
2 桂林电子科技大学生命与环境科学学院, 广西 桂林 541004
晚期糖基化终末产物（AGEs）是一种结构多样的化合物, 在人体血糖高于正常范围时, 会大量产生且不能通过自身代谢降解, 具有血糖长期异常的记忆作用。 研究表明AGEs是引起糖尿病及其并发症的重要因素之一, 通过检测体内AGEs的积累情况可以预测糖尿病及其并发症的发生和发展进程。 现有的离体AGEs检测方法存在操作复杂、 时间较长、 成本较高和不易推广等问题; 在体AGEs检测方法存在皮肤色素、 年龄和血红蛋白干扰等问题。 为此, 基于角膜良好的光学特性和AGEs的自体荧光特性, 提出一种角膜晚期糖基化终末产物荧光光谱检测方法。 构建了一套角膜AGEs荧光光谱检测系统, 系统由微型光纤光谱仪、 集成LED激发光源、 Y型12+1光纤和PC端光谱处理显示软件组成。 荧光光谱检测系统采用激发光源波长分别为370和395 nm在暗室条件下对17名志愿者（男性9人, 女性8人, 糖尿病患者4人, 年龄最小15周岁, 最大81周岁）进行数据采集, 得到激发光波长分别为370和395 nm的荧光光谱数据。 为了准确识别荧光光谱中的有用信息, 先截取需要的荧光光谱数据段（450~700 nm）, 然后对其进行去除背景噪声、 归一化、 小波变化等方法处理, 可以将荧光光谱中不明显的荧光峰值进行放大和识别。 实验结果发现, 采用波长为370和395 nm的LED作为激发光源, 检测到角膜发射的荧光光谱范围在420~600 nm内, 并且都分别在450~500, 500~550和550~600 nm三个范围内存在光谱峰值。 根据荧光性物质的荧光峰值与激发光波长无关的原理, 表明两种不同波长的激发光所得到的荧光光谱都是由同一种物质AGEs产生。 对糖尿病患者和正常人的荧光峰值强度进行分析, 显示糖尿病患者的荧光强度明显高于正常人, 表明本研究通过荧光光谱法检测角膜晚期糖基化终末产物具有可行性。
角膜 晚期糖基化终末产物(AGEs) 荧光光谱 无创检测 Cornea Advanced glycation end products (AGEs) Fluorescence spectroscopy Noninvasive detection 光谱学与光谱分析
2021, 41(4): 1055
1 南开大学 电子信息与光学工程学院 现代光学研究所，天津 300350
2 天津市微尺度光学信息技术科学重点实验室，天津 300350
3 北京大学眼视光学研究中心，北京 100027
本文提出了一种新的角膜面形分析方法，不仅消除了角膜本体厚度对塑形后角膜面形分析的影响，同时也能体现塑形后角膜的不对称性。在角膜前表面高度数据分析中引入基准参考面，以消除角膜本体厚度的影响，进而将塑形后的角膜前表面划分为光学区、转换区和边缘区。分析表明，角膜塑形后的光学区口径为（1.9±0.27） mm，曲率半径为（8.32±0.38） mm；转换区口径为（6.56±0.38） mm，曲率半径为（7.48±0.55） mm；边缘区的曲率半径为（10.49±1.83） mm。角膜塑形后的转换区水平方向屈光能力小于竖直方向的屈光能力，鼻侧屈光能力大于颞侧屈光能力，上侧屈光能力大于下侧屈光能力。利用所得参数建立半定制化的眼模型，对眼模型进行分析，结果表明：角膜塑形后周边呈近视性离焦，各方向的离焦呈非对称性分布，符合临床表现。
角膜塑形镜 角膜分区 周边离焦 分区算法 眼模型 orthokeratology lens division of cornea peripheral defocus partition algorithm eye model
Author Affiliations
Abstract
1 Department of Biomedical Engineering, The Ohio State University, Columbus, OH 43210, USA
2 Biophysics Interdisciplinary Group, The Ohio State University, Columbus, OH 43210, USA
3 Department of Ophthalmology and Visual Science, The Ohio State University, Columbus, OH 43210, USA
The three-dimensional (3D) mechanical response of the cornea to intraocular pressure (IOP) elevation has not been previously reported. In this study, we use an ultrasound speckle tracking technique to measure the 3D displacements and strains within the central 5.5mm of porcine corneas during the whole globe inflation. Inflation tests were performed on dextran-treated corneas (treated with a 10% dextran solution) and untreated corneas. The dextran-treated corneas showed an inflation response expected of a thin spherical shell, with through-thickness thinning and in-plane stretch, although the strain magnitudes exhibited a heterogeneous spatial distribution from the central to more peripheral cornea. The untreated eyes demonstrated a response consistent with swelling during experimentation, with through-thickness expansion overriding the inflation response. The average volume ratios obtained in both groups was near 1 confirming general incompressibility, but local regions of volume loss or expansion were observed. These results suggest that biomechanical measurements in 3D provide important new insight to understand the mechanical response of ocular tissues such as the cornea.
Ultrasound speckle tracking cornea inflation 3D Journal of Innovative Optical Health Sciences
2017, 10(6): 1742005
1 复旦大学 电子工程系，上海 200433
2 医学影像计算及计算机协助介入重点实验室 上海 200433
3 香港理工大学 跨学科生物医学工程部门，香港
4 首都医科大学 附属北京同仁医院 北京市眼科研究所，北京 100005
5 中国人民解放军总医院 眼科系，北京 100853
基于角膜测量仪器Corvis ST采集的图像视频，提出提取新特征参数以便准确区分正常角膜和圆锥角膜。首先对图像进行滤波、分割等预处理，检测角膜上下边界，并计算前角膜曲率值; 用小波变换分析角膜曲率变化，获取与角膜运动趋势相关的特征，包括角膜运动的整体趋势和角膜振动的范数和标准差。然后，基于均方误差最小化法，提取特征参数，构建最优参数。最后，用支持向量机(SVM)对正常角膜和圆锥角膜进行分类。从频率的角度实施的实验显示角膜在基本运动趋势上存在着振动过程。此外，提出的参数优于形变幅度(DA)、峰值距离(PD)等传统参数，使准确度、灵敏度和特异性分别提高了10.2%，5.7%和6.9%。受试者工作特征曲线 (ROC)下面积为0.948，接近于1。结果显示本文方法自动提取的特征参数可提高正常角膜和圆锥角膜区分的准确性，对临床诊断有辅助作用。
角膜 圆锥角膜 特征提取 最小均方误差算法 小波变换 cornea keratoconic cornea feature extraction minimum mean square error algorithm Corvis ST Corvis ST wavelet transform 光学 精密工程
2015, 23(10): 2919
Author Affiliations
Abstract
Department of Computer Science and Technology Tsinghua University, Beijing 100084, P. R. China
Manual analysis of anterior segment optical coherence tomography (AS-OCT) images is fairly time consuming, and inter-observer reproducibility cannot be guaranteed. Therefore, automated analysis methods of AS-OCT images are necessary in clinical applications. This paper presents a novel approach to extract the inner contour of the anterior chamber automatically from AS-OCT images using a \divide-and-conquer" strategy. We first find the anchor points in an image and these points are used to divide the image into subimages where the iris, lens and cornea are located. Then the endothelial surface of the cornea, lens surface and iris surface are obtained from these subimages with different schemes, and they are merged together to obtain the complete inner contour. In our method, the endothelial surface of the cornea is fitted by using three circular arcs under continuity constraints. Experiments show that the proposed algorithm can extract the inner contour of the anterior chamber from AS-OCT images accurately in real time.
Computer-aided diagnosis endothelial surface of the cornea divide-and-conquer strategy Journal of Innovative Optical Health Sciences
2012, 5(4): 1250030
1 军事医学科学院放射与辐射医学研究所, 北京 100850
2 中国人民解放军总医院第一附属医院皮肤科, 北京 100048
目的: 实验研究脉冲1.338 μm激光的角膜损伤效应, 确定其损伤阈值, 并与10.6 μm激光角膜损伤特点进行比较。方法: 采用输出波长1.338 μm、脉冲宽度5 ms的Nd: YAG激光为照射光源, 角膜光斑直径1.7 mm, 以不同剂量的激光照射新西兰白兔角膜, 于照后1 h观察角膜损伤情况, 统计损伤发生率, 采用加权概率单位法计算损伤发生率为50%时所对应的激光剂量, 即损伤阈值ED50。在1.5倍阈值剂量下比较该激光与10.6 μm激光角膜损伤的特点。实验中注意观察晶状体和眼底是否有损伤。结果: 脉冲1.338 μm激光角膜损伤阈值为27.0 J/cm2(95%置信区间25.8~28.1 J/cm2)。阈值水平下, 角膜损伤斑肉眼观察呈淡淡的灰白色, 裂隙灯下可见一与角膜同厚的灰白色反光带, 晶状体或视网膜正常; 1.5倍阈值剂量下, 角膜损伤斑为清晰的瓷白色, 裂隙灯下可见一与角膜同厚的白色反光带, 同时观察到晶状体前表面白色反光点, 但视网膜无变化。与之相比, 10.6 μm激光角膜损伤在裂隙灯下仅观察到一很窄的亮白反光条, 位于角膜表层。结论: 脉冲1.338 μm激光在光斑直径1.7 mm, 脉冲宽度5 ms条件下的角膜损伤阈值为27.0 J/cm2。角膜损伤特点是, 损伤斑呈灰白色或瓷白色, 累及角膜全层, 而10.6 μm激光损伤仅累及角膜浅层。
脉冲1.338 μm激光 角膜 损伤效应 损伤阈值 pulsed 1.338 μm laser cornea damage effect threshold
1 军事医学科学院放射与辐射医学研究所, 北京 100850
2 军事医学科学院国家生物医学分析中心, 北京 100850
3 军事医学科学院附属307医院, 北京 100071
为了研究激光照射后角膜蛋白质化学组成的改变, 探讨激光角膜损伤的发生机制, 将日本大耳白兔随机分为正常对照组和激光损伤组, 选取角膜上皮层和基质层作为研究对象, 通过傅里叶变换红外光谱技术(Fourier transform infrared spectroscopy, FT-IR)对角膜组织酰胺I带中蛋白质二级结构各吸收峰进行定量分析, 观察激光照射后蛋白质分子结构的改变情况。结果显示, 激光照射后出现蛋白质二级结构吸收峰的位移和积分百分比的改变。激光照射可使角膜上皮层和基质层蛋白质构象发生改变, 从而导致蛋白质结构稳定性下降和蛋白质生物功能的破坏。
激光 角膜 蛋白质 光谱 结构 laser cornea protein spectroscopy structure
