江慧绿

, 李超宏

, 廖娜

, 厉以宇

, 陈浩

. . 可调焦自适应光学扫描激光眼底成像系统设计. 光学学报, 2019, 56(2): 022202-。

Jiang Huilü

, Li Chaohong

, Liao Na

, Li Yiyu

, Chen Hao

. . Optical Design of Adaptive Optics Scanning Laser Ophthalmoscope with Adjustable Focus. Acta Agronomica Sinica, 2019, 56(2): 022202-.

可调焦自适应光学扫描激光眼底成像系统设计

江慧绿1,2, 李超宏1, 廖娜1,2, 厉以宇1,2, 陈浩1,2*

1温州医科大学眼视光学院, 浙江 温州 325027

2温州医科大学附属眼视光医院, 浙江 温州 325027

摘要

自适应光学扫描激光眼底成像系统研究是当前研究的一个热点。利用Badal系统、变形镜和夏克-哈特曼波前传感器设计了一种可调焦的自适应光学激光扫描眼底成像系统,通过视标引导,调节Badal系统中的透镜间距,实现人眼低阶像差校正。根据系统调焦及工作原理,分析了Badal系统最佳参数,并对系统参数进行设计,采用Zemax光学软件对系统进行仿真及优化。仿真结果表明,设计的系统点列图光斑小于衍射极限,各屈光度斯特列尔比值均大于0.8,甚至低屈光度下的斯特列尔比可达0.95,不同屈光度下各视场调制传递函数(MTF)曲线接近衍射极限,正常人眼视网膜面上系统理论分辨率约为2.29 μm,接近衍射极限分辨率(2.11 μm),能够对-6~6 m-1屈光不正的人群实现眼底视网膜清晰成像。

关键词

光学设计; 眼底成像系统; 屈光补偿; 像质评价

Optical Design of Adaptive Optics Scanning Laser Ophthalmoscope with Adjustable Focus

Jiang Huilü1,2, Li Chaohong1, Liao Na1,2, Li Yiyu1,2, Chen Hao1,2*

1School of Ophthalmology & Optometry, Wenzhou Medical University, Wenzhou, Zhejiang 325027, China;

2Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325027, China

Abstract

Adaptive optics scanning laser ophthalmoscopy (AOSLO) has gained increased research attention over the past few decades. This study proposes a focus-adjustable AOSLO that uses a novel optical design comprising a Badal system, a deformable mirror, and a Shack-Hartmann wavefront sensor. This design corrects the low-order aberration of the human eye by setting a target and adjusting the distance between lenses in the Badal system. The optimum parameters of the Badal system based on the focusing and working principle of the system are analyzed; then, the system is simulated and optimized by Zemax software. Simulation results show that the spot size of the proposed system is smaller than the diffraction limit in the spot diagram. The Strehl ratio of any diopter is more than 0.8 and approaches as high as 0.95 for a low diopter. The modulation transfer function of every field approaches the diffraction limit. Moreover, the theoretical resolution in the normal human retina of this system (2.29 μm) is in a close range to the diffraction-limit resolution of the proposed system (2.11 μm). The proposed system can achieve a clear imaging of the human retina for people with a diopter from -6 m-1 to +6 m-1.

Key words

optical design; ophthalmic imaging system; diopter compensation; image quality evaluation

论文信息

doi:10.3788/LOP56.022202

OCIS codes:

220.4830; 110.1085; 170.5755

收稿日期:2018-09-07

接受日期:2018-09-14

基金项目:国家重点研发计划、温州市科技计划Y20160153

1 引言

人眼视网膜生物组织结构(如视细胞、微血管等)及功能的好坏, 决定了人眼的视觉成像质量, 并且人体全身系统性疾病(如糖尿病、高血压、动脉硬化等)也都会在眼底视网膜上有所反映, 因此, 眼底检查无论在视觉研究还是在疾病早期诊断方面都具有十分重要的意义[。由于人眼是一个动态变化的、不完善的光学系统[, 而现有的常规眼底成像设备[只能校正静态像差, 其分辨率(10~15 μm[)无法满足对疾病早期微小病变检测的要求。为了克服人眼像差的影响, Liang等[首次采用夏克-哈特曼波前传感器(SHWFS)成功探测到人眼的波前像差, 搭建了基于自适应光学(AO)技术的视网膜成像系统, 并获得接近衍射极限的活体人眼视网膜细胞图像。此后基于自适应光学视网膜成像系统得到了广泛的研究[首次将AO技术与共焦扫描激光检眼镜结合搭建了实验系统, 极大地提高了系统的横向、纵向成像分辨率, 获得了视细胞、毛细血管血流等高分辨率图像。

然而, 目前报道的自适应光学眼底成像系统存在普适性不够、杂散光较多、图像质量不高等问题, 普适性对于系统产品化具有非常重要的作用, 普适性不够是指不能对大部分受试者都能获得清晰的视网膜图像, 这是由于人眼普遍存在屈光不正(如近视、远视等), 其屈光不正范围跨度比较大, 因此, 系统需要同时具有大幅值的低阶像差校正能力和较强的高阶像差校正能力。已报道的方法有:1) 使用离焦和散光补偿片校正人眼低阶像差, 剩余的高阶像差由波前校正器校正, 其缺点是补偿的数值不连续, 需要大量的补偿片, 手动补偿, 操作不方便, 增加了系统使用的复杂度, 不适合产品化, 改变了系统的共轭位置, 从而降低人眼像差测量的准确性及校正效果等; 2) 采用双变形镜(dual-DM)校正人眼低阶像差和高阶像差-1屈光度), 不利于产品化等, 如Chen等[采用双变形镜校正人眼像差, 35单元Bimorph变形镜校正人眼低阶像差, 144单元微机电(MEMS)变形镜校正人眼高阶像差, Zou等[。

针对上述问题, 为了提高低阶像差校正能力, 本文采用Badal调焦技术

2 原理及结构

2.1 Badal系统调焦原理

对于平行光, 即无穷远处的物点, Badal系统一般由两个正透镜组合而成, 焦点重合时为望远系统, 入瞳位于前透镜前焦点处, 出瞳位于后透镜后焦点处, 前透镜对无穷远处的物点成像, 后透镜调节系统的焦距, 通过改变两透镜间在光轴方向的距离实现对系统焦距的调节, 在保证系统共轭位置不变的前提下实现对离焦的补偿。因此, 对于相同焦距的两透镜, Badal系统具有如下特点:随着透镜间距的改变, 1) 光瞳(入瞳和出瞳)始终位于透镜焦点处, 光瞳处系统垂轴放大率始终为-1; 2) 光瞳处系统角放大率始终为-1, 视场角不发生改变; 3) 系统等效焦距发生变化, 可补偿人眼屈光不正。

AOSLO系统设计是以无像差人眼为前提, 实现系统像差校正, 照明光通过系统以平行光方式进入到人眼眼底, 眼底反射光以平行光方式返回进入到AOSLO系统。但实际上人眼具有动态像差, 且不同人眼的屈光度数不同, 如近视、远视等, 因此, 对于不同屈光度的人眼眼底进行成像时需要对光学系统调焦。采用Badal系统, 根据光瞳衔接原则, 人眼瞳孔和AOSLO系统入瞳分别位于Badal系统前后的透镜焦点处, 实现人眼屈光不正补偿。对于相同焦距的Badal系统, 视场角不发生变化, 光瞳口径不发生变化, 因此Badal系统的引入不影响原系统的成像特性。其Badal系统两透镜间的移动量依赖人眼屈光度数的变化, 如图1(a)所示。假设前透镜不动, 后透镜移动, 人眼瞳孔位于后透镜像方焦点处, 初始状态为两透镜焦点重合, 根据牛顿公式可得, 后透镜从初始状态到目前状态的移动量为

Δ=Df'221000,(1)

式中:Δ为透镜移动量, 单位为mm, Δ< 0表明后透镜左移, Δ> 0表明后透镜右移; D为人眼屈光度, 单位为m-1, D< 0代表近视, D> 0代表远视; f'2为后透镜焦距, 单位为mm。

图1

Fig. 1

图1 Badal系统结构示意图。(a)展开式Badal系统原理示意图, 红色标记为调焦后的状态; (b)折叠式Badal系统结构示意图Fig. 1 Structure diagram of Badal system. (a) Schematic diagram of unfolded Badal system, the red represents state after focusing; (b) structure diagram of folded Badal system

在实际AOSLO系统中, 为了使人眼和透镜保持不动, 一般采用折叠式Badal系统, 即两透镜间加入4块平面反射镜, 如图1(b)所示, 其中两块平面反射镜P1保持不动, 另两块平面反射镜P2相对P1作直线运动, 通过移动反射镜P2来实现两透镜间光程的改变, 则反射镜P2移动量为Δ/2。

2.2 AOSLO系统结构及原理

如图2所示, AOSLO系统由视标引导的屈光补偿系统、照明光路系统、自适应成像光路系统组成。其中视标引导的屈光补偿系统包括视标光路系统和Badal系统, 自适应成像光路系统包括像差探测与校正系统、振镜扫描系统、图像采集系统。为提高眼底照明质量, 使系统紧凑, 照明光路采用部分共用的光路照射人眼眼底, 即与自适应成像光路系统共用像差校正、振镜扫描和Badal系统等部分光路, 使入射眼底的照明光会聚到眼底, 在视网膜面上形成理想的像点。为方便后期系统调试与修改, Badal系统中两透镜采用相同的焦距。像差探测与校正系统采用SHWFS探测波前像差, 采用DM校正波前像差。振镜扫描系统采用垂直扫描振镜(VS)和水平扫描振镜(HS)形成二维光栅扫描, 图像采集系统采用光电倍增管(PMT)作为成像探测器, 收集每个眼底扫描点反射光的强度值, 作为图像像素点。DM、VS、HS和Badal系统间采用两球面反射镜组成的望远系统(M1-M8)进行衔接, 其中反射镜M1-M8主要作用如下:1) 改变光路传播方向, 使系统紧凑; 2) 实现扩束或缩束作用, 使光束直径满足振镜、变形镜、瞳孔口径的要求。

图2

Fig. 2

图2 自适应光学扫描激光眼底成像系统光路结构Fig. 2 Optical path of AOSLO

系统的工作过程如下:视标发出的光经透镜L3准直, 通过二色分光镜D1反射耦合进入到照明光路系统中, 经过Badal系统, 进入到人眼眼底。视标可诱导人眼自动调节并稳定人眼屈光度, 再结合Badal系统, 补偿人眼屈光度, 使照明光入射会聚到眼底视网膜面上的像点尽量小。人眼经Badal系统、D1、透镜L3凝视视标, 通过人眼自动调焦以及调节Badal系统反射镜P1和P2之间的距离, 使人眼看清视标, 此时, 基本校正了人眼的离焦像差。

超辐射发光二极管(SLD)经准直器准直后, 依次经薄膜分束片(PB1)、望远系统M1~M2、DM、望远系统M3~M4、HS、望远系统M5~M6、VS、望远系统M7~M8、平面反射镜(FM2)、Badal系统等光学元件照射人眼。带有人眼像差的眼底反射光由人眼出射后, 反方向依次经过上述一系列光学元件, 透过PB1, 再次经过PB2、透镜L6、FM1、光阑(ID)、透镜L5等光学元件进入SHWFS, 其中ID主要目的是滤去系统中产生的杂散光, 提高像差探测精度。SHWFS探测系统及人眼波前像差, 通过CCD接收经微透镜阵列分割的波前信息并传递给计算机, 通过控制软件完成波前重构, 并驱动变形镜面型改变, 实现系统像差校正。

最后, 重复上一个步骤, SLD光源经上述光学元件, 由PB2透射之后经透镜L4聚焦在成像探测器PMT上, 在PMT前放置针孔(PH), 人眼视网膜成像在PH面上, 滤掉系统中产生的杂散光, 通过PMT记录经针孔后的像点光强值, 作为图像像素值, 通过二维光栅扫描眼底成像区域, 依次通过PMT采集各像点光强值, 通过软件重构出眼底图像。

2.3 AOSLO系统调焦最佳参数

AOSLO系统采用的是折叠式Badal系统, 在两透镜间需放置一些光学元件, 如平面反射镜, 因此两透镜间需预留一些空间。而透镜间光程均与透镜焦距和人眼屈光度有关, 如图1所示, 由(1)式可得, 在两透镜焦距相同的前提下, 透镜间光程(单位为mm)为

S=2f'2+Dmf'221000,(2)

式中:Dm为最大近视屈光补偿量。为了保守起见, 要求预留空间尽量大, 同时Badal调焦范围也要求尽量宽。由(2)式可知, 只需考虑在最大近视屈光补偿状态下的透镜间光程, 即为所要求的预留空间。其中, 当f'2=-1000/Dm时, S取最大值, 此时Smax=-1000/Dm, 在不同最大近视屈光补偿状态下的最佳透镜焦距和最大透镜间光程如表1所示, 可以看出, 随着最大近视屈光补偿量的增大, 最佳透镜焦距和最大透镜间光程则随之减小, 因此需综合考虑预留空间与Badal调焦范围, 在保证能放入光学元件的前提下, 尽量扩大Badal调焦范围。

表1

Table 1

Optimum parameters of Badal system for different maximum myopia diopters

Table 1表1 不同最大近视屈光度下的Badal系统最佳参数      Table 1 Optimum parameters of Badal system for different maximum myopia diopters

表1不同最大近视屈光度下的Badal系统最佳参数Table 1Optimum parameters of Badal system for different maximum myopia dioptersMaximummyopiadiopter /m-1Optimumlens focallength /mmMaximum opticalpath betweenlenses /mm-8.0125.00125.00

-7.5133.33133.33

-7.0142.86142.86

-6.5153.85153.85

-6.0166.67166.67

-5.5181.82181.82

-5.0200.00200.00

-4.5222.22222.22

-4.0250.00250.00

-3.5285.71285.71

-3.0333.33333.33

如图2所示, Badal系统中两透镜间加入4块平面反射镜, 通过移动反射镜来实现两透镜间光程的改变。考虑到系统扫描角和视标视角, 平面反射镜采用50.8 mm×50.8 mm口径的反射镜, 对于45°摆放, 需预留的空间为50.8/ 2×4=143.68 mm。根据表1, 最大近视屈光补偿度数D≥-6.5 m-1。为了保守起见, 预留更多空间, 这里最大近视屈光补偿度数可取-6 m-1, 此时最佳透镜焦距为166.67 mm。考虑到实际市面上存在的透镜, 焦距可取150 mm, 此时, Badal调焦范围为-6~6 m-1, 反射镜P2移动范围ΔP2为-67.5~67.5 mm。

3 光学系统设计

3.1 参数设计

根据上述分析的系统结构以及实际要求, 主要设计参数如表2所示, 具体分析如下。

入瞳:对于成像光路, 采用人眼瞳孔作为AOSLO系统的入瞳, 正常情况下人眼瞳孔直径为2~8 mm[, 考虑到系统分辨率, 尽量取较大的瞳孔作为系统入瞳, 再结合变形镜通光口径, 这里取入瞳直径为6.6 mm。

光源:像差探测光源和成像光源采用同一种光源。为保证系统成像质量达到最佳, 尽量选用波长较短、视网膜反射率较高[、眼睛舒适、宽带宽激光光源; 为避免影响图像质量尽量消除相干光引起的斑点[。采用波长为785 nm的SLD光源。

视场:考虑到人眼等晕角, 从等晕区域出射的光其像差变化很小, 该区域视网膜的成像质量可认为是不发生变化的, 这样只需校正该区域内的某个像素点像差就可以实现整个区域的像差校正。由于AO校正频率较慢, 一帧图像中估计只能校正某个像点的像差, 所以需在尽量接近等晕角区域内成像, 提高整个成像区域的像差校正能力。据报道, 瞳孔直径为6 mm, 其等晕角约为2°(圆)[, 而瞳孔直径为4~6 mm, 其等晕角则小于2.5°×2.5°[, 这里取2.5°×2.5°作为视场角设计指标, 即±1.25°×±1.25°。

屈光补偿范围:尽量满足大多数患者的要求, 即能校正大多数远视眼和近视眼引起的屈光不正, 根据上述分析的结果, 屈光补偿范围为-6~6 m-1。

波前校正器:1) 考虑到采用Badal系统校正低阶像差, 变形镜校正高阶像差, 因此需采用高精度波前校正器; 2) 变形镜驱动单元数越多, 变形镜重构的面型精度越高; 3) 考虑到变形镜精度能充分利用, 其驱动单元数尽量与微透镜阵列有效单元数匹配; 4) 采用市面上已有的产品, 在满足以上条件下尽量减小产品成本。综上考虑, 采用140单元Multi-DM微机械可变形反射镜, 该反射镜具有功能多样、技术成熟、高分辨率波前校正能力等特点, 具体参数为:140个驱动器, 最大行程3.5 μm, 通光口径4.4 mm×4.4 mm。

波前传感器:SHWFS由微透镜阵列与CCD相机组合而成。微透镜具体参数:大小10 mm×10 mm, 透镜间间距为300 μm, 有效焦距为18.6 mm; CCD具体参数:1360 pixel×1024 pixel, 像素尺寸6.45 μm×6.45 μm, 芯片尺寸8.8 mm×6.6 mm。

成像探测器:采用光电倍增管, 有效感光面的直径为5 mm。

扫描振镜:横向振镜采用扫描频率为11 kHz的共振扫描振镜, 镜片有效面积为4 mm×4 mm。纵向扫描振镜采用检流计扫描振镜, 镜片有效面积为8 mm×12 mm。

表2

Table 2

Parameters of optical design

Table 2表2 光学设计参数      Table 2 Parameters of optical design

表2光学设计参数Table 2Parameters of optical designEntrancepupildiameter /mmSLDwavelength /nmField ofview /(°)Dioptercompensationrange /m-1DM clearaperture /mm×mmCCD senordimensions /mm×mmPMTeffectivearea /mmHSscannereffectivearea /mm×mmVS scannereffective area /mm×mm6.6785±1.25-6-+64.4×4.48.8×6.6Φ54×48×12

3.2 光学设计

3.2.1 屈光补偿系统

依据上述分析的原理及参数, 视标引导的屈光补偿系统采用视标诱导人眼自动调焦, 结合Badal系统, 校正不同屈光度人眼离焦像差引起的系统像差。其视标采用590 nm波长的光, 移动定位区域视场设定为±4°。为了减小周围视场的像差, 可在视标附近瞳孔共轭处放置4 mm直径的光阑, 其视标的作用是可诱导人眼自动调焦并稳定人眼屈光度, 同时也可引导定位眼底不同的拍摄区域; 折叠式Badal调焦系统作用是缩短光路, 辅助人眼调焦, 保证人眼能看清视标。采用Zemax光学设计软件对屈光补偿系统进行设计和优化, 仿真中要求系统在±4°视场内视标成像质量良好, 人眼能看清视标, 畸变小; 此外, 再结合眼底照明及成像光路系统的像质要求, 则要求系统在±1.25°×±1.25°视场内眼底照明成像质量接近衍射极限。在Zemax光学设计软件中, 为确保人眼能够看清无穷远处的视标像, 采用理想透镜来准直视标, 模拟无穷远处的视标, Zemax仿真的模型如图3所示。

图3

Fig. 3

图3 屈光补偿系统Zemax设计图Fig. 3 Design of diopter compensation system using Zemax

3.2.2 照明成像系统

依据上述分析的原理及参数, 人眼低阶像差(离焦像差)由Badal系统校正, 人眼高阶像差由变形镜校正, 采用Zemax光学设计软件对眼底照明及成像系统进行设计和优化, 分析系统本身的成像质量及人眼视网膜面上的分辨率。在Zemax软件仿真中, 其中DM由平面反射镜代替; 由于正常人眼的空气等效焦距为17.1 mm[, 采用焦距为17.1 mm的理想透镜及接收屏置于空气中来模拟人眼; 由于眼轴变化使得焦点离开视网膜面, 造成人眼屈光不正, 因此通过改变模拟眼透镜与接收屏的距离来模拟人眼屈光度。由于照明光路系统与自适应成像光路系统共用部分光路系统, 其照明光路与成像光路互为可逆光路, 这里统称为照明成像系统, 采用照射人眼的光路来评价照明成像系统的像质, 光路图如图4所示, 主要元件具体参数(正负号按照Zemax符号规定)可见表3所示。其系统设计依据如下:1) 光束直径尽量充满整个变形镜口径, 满足各元件口径要求; 2) 保证系统振镜、变形镜和瞳孔间的共轭关系; 3) 为各器件留下足够的摆放空间。其在DM、HS、VS和出瞳面处光斑直径分别为4.4, 3.3, 6.6, 6.6 mm。

图4

Fig. 4

图4 照明成像光路系统Zemax设计图Fig. 4 Design of lighting and imaging optical systems using Zemax

表3

Table 3

Configuration parameters

Table 3表3 结构参数      Table 3 Configuration parameters

表3结构参数Table 3Configuration parametersConcave mirrorf /mmDiameter/mmTilt X /(°)M130025.43

M220025.4-6.5

M320025.4-6.5

M415025.45

M520050.85

M640050.8-5

M730050.8-5.5

M830050.85

4 光学性能评价

4.1 屈光补偿系统

为了人眼能看清视标, 便于人眼屈光度补偿, 稳定人眼屈光度, 引导定位拍摄区域, 要求视标在人眼视网膜面上所成的像具有良好的成像质量, 其正常人眼的点列图、场曲和畸变如图5和图6所示。光线点列图是一种不考虑衍射且原理简单的像质评价方法, 一般认为, 点列图的弥散斑若控制在艾里斑范围之内, 可认为光学系统成像为理想成像。由图5和图6可知, 在±4°视场内系统各视场点列图均方根(RMS)半径分别为0.519, 0.759, 0.759, 3.076, 3.076 μm(590 nm波长), 接近艾里斑大小(半径为3.097 μm), 系统畸变在全视场范围内小于0.01%, 场曲小于0.05 mm, 视标成像质量良好。而在±1.25°×±1.25°视场内系统点列图RMS半径小于0.9 μm(785 nm波长), 小于艾里斑半径, 达到衍射极限, 则Badal系统对AOSLO系统眼底成像基本不引入新的像差。

图5

Fig. 5

图5 不同视场下的屈光补偿系统光线点列图。(a) 0.590 μm波长, (b) 0.785 μm波长Fig. 5 Spot diagrams of diopter compensation system with different fields of view. (a) 0.590 μm wavelength; (b) 0.785 μm wavelength

图6

Fig. 6

图6 屈光补偿系统场曲和畸变图Fig. 6 Field curvature and distortion of diopter compensation system

4.2 照明成像系统

斯特列尔(Strehl)准则同样是一种高质量的像质评价标准, 适用于小像差光学系统, 当斯特列尔比大于0.8时, 认为光学系统的成像质量是完善的, 对于共焦激光扫描点成像系统, 收集的是像点的光强度, 滤掉像点周围的杂散光, 因此, 斯特列尔比越高, 则中心点亮度越亮, 信息损失越少, 成像越清晰。调制传递函数(MTF)是一种比较全面的像质评价方法, 能同时运用于小像差光学系统和大像差光学系统。图7、表4和图8分别给出了该AOSLO系统不同结构和屈光度下光线的点列图、斯特列尔比和MTF, 即0°、±1°、±1.25°视场角(X和Y方向), 具体结构对应的视场如表4所示, 图7中黑色圆为艾里斑圆, 即衍射极限大小, 图8中最上方的黑色曲线(Diff. limit)为衍射极限状态下的MTF值。由图7可知, 设计的系统点列图光斑小于衍射极限, 因此, 可判定此系统在±1.25°×±1.25°视场范围内成像较理想, 接近于衍射极限状态。由表4可知, 5种屈光度中的斯特列尔比分别为0.939, 0.959, 0.967, 0.948, 0.864, 斯特列尔比值均大于0.8, 尤其低屈光度数下的斯特列尔比高达0.95左右, 成像质量良好。由图8可知, 不同屈光度下各视场MTF曲线十分接近衍射极限, 且正常人眼(屈光度为0 m-1)在437.56 cycles·mm-1处的MTF值为0.026(目视分辨率极限), 其对应的系统人眼视网膜面上分辨率约为2.29 μm, 接近系统人眼视网膜面上极限分辨率(道威判据2.11 μm)[。

图7

Fig. 7

图7 不同结构和屈光度下的光线点列图Fig. 7 Spot diagrams for different configurations and diopters

表4

Table 4

Strehl ratio analysis at different fields-of-view, from -1.25° to 1.25° at eye pupil

Table 4表4 不同视场(瞳孔处±1.25°)下斯特列尔比分析      Table 4 Strehl ratio analysis at different fields-of-view, from -1.25° to 1.25° at eye pupil

表4不同视场(瞳孔处±1.25°)下斯特列尔比分析Table 4Strehl ratio analysis at different fields-of-view, from -1.25° to 1.25° at eye pupilConfiguratonStrehl ratioNo.Field (X, Y) /(°)-6 m-1 diopter-3 m-1 diopter0 m-1 diopter+3 m-1 diopter+6 m-1 diopter

1(0, 0)0.9300.9370.9370.9730.984

2(0, 1)0.9360.9510.9580.9740.931

3(1, 0)0.9390.9550.9630.9720.930

4(0, 1.25)0.9380.9560.9650.9670.919

5(0, -1.25)0.9380.9580.9730.9840.911

6(1.25, 0)0.9420.9620.9720.9600.904

7(-1.25, 0)0.9420.9620.9720.9600.904

8(1.25, 1.25)0.9420.9670.9730.9050.755

9(1.25, -1.25)0.9390.9650.9750.9150.753

10(-1.25, 1.25)0.9420.9670.9730.9050.755

11(-1.25, -1.25)0.9390.9650.9750.9150.753

Average0.9390.9590.9670.9480.864

图8

Fig. 8

图8 不同结构和屈光度下的调制传递函数图。(a)屈光度为0 m-1; (b)屈光度为-6 m-1; (c)屈光度为+6 m-1Fig. 8 Modulation Transfer Functions for different FOV. (a) 0 m-1 diopter; (b) -6 m-1 diopter; (c) +6 m-1diopter

5 公差分析

针对本文设计的AOSLO系统特点, 从光学零件加工与装配等方面考虑, 设定整个系统各结构参数的具体公差, 见表5所示。选用正常人眼(屈光度为0 m-1)在(0, 1°)视场处的RMS光斑半径作为评价指标。通过公差灵敏度独立分析发现, 对系统性能影响较大的因素主要是变形镜和扫描振镜的倾斜误差, 其RMS光斑半径下降0.7~0.8 μm。通过蒙特卡罗公差交互分析, RMS光斑半径变化范围在0.5~2.0 μm之间, 其变化范围均在艾里斑半径范围内, 变化幅度可以接受。

表5

Table 5

Tolerance data of optical system

Table 5表5 光学系统公差数据      Table 5 Tolerance data of optical system

表5光学系统公差数据Table 5Tolerance data of optical systemParametersRangeRadius of curvature /mm±1

Thickness /mm±0.2

Element decenter /mm±0.1

Element tilt /(°)±0.1

Surface irregularity /fringes±0.2

Index of refraction±0.001

6 结论

设计了一种可调焦的自适应光学激光扫描眼底成像系统, 可实现屈光不正的连续补偿, 可适用于-6~6 m-1屈光不正的人群, 对±1.25°×±1.25°视场内眼底视网膜可清晰成像。通过诱导人眼凝视视标, 调节Badal系统中透镜间间距, 可实现人眼低阶像差(离焦像差)校正, 使残余像差在变形镜校正范围内, 从而实现人眼高低阶像差的自动校正功能。设计的系统点列图光斑小于衍射极限, 各屈光度斯特列尔比值均大于0.8, 成像质量良好, 不同屈光度下各视场MTF曲线十分接近衍射极限, 正常人眼视网膜面上系统理论分辨率约为2.29 μm, 接近衍射极限分辨率(2.11 μm); 其中视标成像质量良好, 点列图光斑接近艾里斑, 畸变小于0.01%。公差分析显示系统具有较好的结构容差, 性能可靠。为后续系统成功搭建以及临床研究奠定了基础。

The authors have declared that no competing interests exist.

作者已声明无竞争性利益关系。

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线扫描共聚焦成像技术基于共聚焦成像原理，使用线光束一维扫描照明样品以提高成像速率；通过共焦狭缝滤除样品成像光束中的非聚焦层面杂散光，提高成像分辨率和对比度；近年来，该技术因分辨率高、成像快、成像视场大、系统结构简单等优点而在生物医学成像中的应用越来越广泛。介绍了线扫描共聚焦成像技术的基本原理，列举了成像系统的主要参数及其影响因素，并举例说明了其在生物医学成像，尤其是眼底成像和生物组织细胞观察等方面的应用，最后总结了该技术的优缺点及其应用前景。

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Kong N N, Li D Y, Xia M L, et al. Liquid crystal adaptive optics system for retinal imaging operated on open-loop and double-pulse mode[J]. Acta Optica Sinica, 2012, 32( 1): 0111002.孔宁宁, 李大禹, 夏明亮, 等. 开环双脉冲液晶自适应光学视网膜成像系统[J]. 2012, 32( 1): 0111002.

为了获得高分辨率视网膜图像，利用液晶空间光调制器作为波前校正器建立了一套开环液晶自适应光学视网膜成像系统。与闭环模式相比，采用开环模式后，系统的能量利用率提高了1倍。系统采用双脉冲照明方式，以减少人眼曝光量，保护人眼安全。在照明光学系统中加入了大小视场切换装置使成像视场由之前的0.8°增至1.7°。同时优化了系统的时序控制流程，对人眼像差连续校正的同时快速调节成像相机的前后位置至最佳像面。对于开环模式对动态人眼像差的校正精度进行了测量，实验测得，经开环校正后，残差波面的均方根值约为0.09λ；相应的斯特雷尔(Strehl)比高于0.70，系统分辨率接近光学衍射极限的分辨率。对两名志愿者进行了实验，获得了清晰的眼底视网膜细胞图像。

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Liang J Z, Grimm B, Goelz S, et al. Objective measurement of wave aberrations of the human eye with the use of a Hartmann-Shack wave-front sensor[J]. 1994, 11( 7): 1949- 1957.

A Hartmann–Shack wave-front sensor is used to measure the wave aberrations of the human eye by sensing the wave front emerging from the eye produced by the retinal reflection of a focused light spot on the fovea. Since the test involves the measurements of the local slopes of the wave front, the actual wave front is reconstructed by the use of wave-front estimation with Zernike polynomials. From the estimated Zernike coefficients of the tested wave front the aberrations of the eye are evaluated. It is shown that with this method, using a Hartmann–Shack wave-front sensor, one can obtain a fast, precise, and objective measurement of the aberrations of the eye.

[本文引用:1]

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Liang J Z, Williams D R, Miller D T. Supernormal vision and high-resolution retinal imaging through adaptive optics[J]. 1997, 14( 11): 2884- 2892.

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Ling N, Zhang Y D, Rao X J, et al. A small adaptive optical imaging system for cells of living human retina[J]. Acta Optica Sinica, 2004, 24( 9): 1153- 1158.凌宁, 张雨东, 饶学军, 等. 用于活体人眼视网膜观察的自适应光学成像系统[J]. 2004, 24( 9): 1153- 1158.

利用自适应光学技术,研制了两套活体人眼视网膜高分辨力成像系统,在实时校正人眼波前误差的基础上,实现活体人眼视网膜细胞尺度的高分辨力成像。这两套系统分别采用19和37单元小型压电变形反射镜作为波前校正元件,哈特曼夏克(Hartmann-Shack)波前传感器测量波前误差,用眼底反射的半导体激光作为波前探测的信标。在用计算机控制自适应光学系统实现人眼波前误差校正后,触发闪光灯照明视网膜,用CCD相机记录视网膜的高分辨力图像。校正后的残余波前误差的均方根值已分别小于1/6和1/10波长,相当于视网膜上成像分辨力分别为3.4 μm和2.6 μm,接近衍射极限。试验表明37单元系统的成像质量更好。

[本文引用:1]

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Rha J, Jonnal R S, Thorn K E, et al. Adaptive optics flood-illumination camera for high speed retinal imaging[J]. 2006, 14( 10): 4552- 4569.

Abstract Current adaptive optics flood-illumination retina cameras operate at low frame rates, acquiring retinal images below seven Hz, which restricts their research and clinical utility. Here we investigate a novel bench top flood-illumination camera that achieves significantly higher frame rates using strobing fiber-coupled superluminescent and laser diodes in conjunction with a scientific-grade CCD. Source strength was sufficient to obviate frame averaging, even for exposures as short as 1/3 msec. Continuous frame rates of 10, 30, and 60 Hz were achieved for imaging 1.8,0.8, and 0.4 deg retinal patches, respectively. Short-burst imaging up to 500 Hz was also achieved by temporarily storing sequences of images on the CCD. High frame rates, short exposure durations (1 msec), and correction of the most significant aberrations of the eye were found necessary for individuating retinal blood cells and directly measuring cellular flow in capillaries. Cone videos of dark adapted eyes showed a surprisingly rapid fluctuation (~1 Hz) in the reflectance of single cones. As further demonstration of the value of the camera, we evaluated the tradeoff between exposure duration and image blur associated with retina motion.

[本文引用:1]

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Roorda A, Romero-Borja F, Donnelly III W J, et al. Adaptive optics scanning laser ophthalmoscopy[J]. Optics Express, 2002, 10( 9): 405- 412.

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Zhang Y, Rha J, Jonnal R S, et al. Adaptive optics parallel spectral domain optical coherence tomography for imaging the living retina[J]. 2005, 13( 12): 4792- 4811.

Abstract Although optical coherence tomography (OCT) can axially resolve and detect reflections from individual cells, there are no reports of imaging cells in the living human retina using OCT. To supplement the axial resolution and sensitivity of OCT with the necessary lateral resolution and speed, we developed a novel spectral domain OCT (SD-OCT) camera based on a free-space parallel illumination architecture and equipped with adaptive optics (AO). Conventional flood illumination, also with AO, was integrated into the camera and provided confirmation of the focus position in the retina with an accuracy of +/-10.3 mum. Short bursts of narrow B-scans (100x560 mum) of the living retina were subsequently acquired at 500 Hz during dynamic compensation (up to 14 Hz) that successfully corrected the most significant ocular aberrations across a dilated 6 mm pupil. Camera sensitivity (up to 94 dB) was sufficient for observing reflections from essentially all neural layers of the retina. Signal-to-noise of the detected reflection from the photoreceptor layer was highly sensitive to the level of cular aberrations and defocus with changes of 11.4 and 13.1 dB (single pass) observed when the ocular aberrations (astigmatism, 3rd order and higher) were corrected and when the focus was shifted by 200 mum (0.54 diopters) in the retina, respectively. The 3D resolution of the B-scans (3.0x3.0x5.7 mum) is the highest reported to date in the living human eye and was sufficient to observe the interface between the inner and outer segments of individual photoreceptor cells, resolved in both lateral and axial dimensions. However, high contrast speckle, which is intrinsic to OCT, was present throughout the AO parallel SD-OCT B-scans and obstructed correlating retinal reflections to cell-sized retinal structures.

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Zhang J, Yang Q, Saito K, et al. An adaptive optics imaging system designed for clinical use[J]. 2015, 6( 6): 2120- 2137.

This publisher’s note amends the author list and Acknowledgments of a recent publication [Biomed. Opt. Express6, 2120 (2015)].

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Zawadzki R J, Choi S S, Jones S M, et al. Adaptive optics-optical coherence tomography: optimizing visualization of microscopic retinal structures in three dimensions[J]. 2007, 24( 5): 1373- 1383.

Adaptive optics-optical coherence tomography (AO-OCT) permits improved imaging of microscopic retinal structures by combining the high lateral resolution of AO with the high axial resolution of OCT, resulting in the narrowest three-dimensional (3D) point-spread function (PSF) of all in vivo retinal imaging techniques. Owing to the high volumetric resolution of AO-OCT systems, it is now possible, for the first time, to acquire images of 3D cellular structures in the living retina. Thus, with AO-OCT, those retinal structures that are not visible with AO or OCT alone (e.g., bundles of retinal nerve fiber layers, 3D mosaic of photoreceptors, 3D structure of microvasculature, and detailed structure of retinal disruptions) can be visualized. Our current AO-OCT instrumentation uses spectrometer-based Fourier-domain OCT technology and two-deformable-mirror-based AO wavefront correction. We describe image processing methods that help to remove motion artifacts observed in volumetric data, followed by innovative data visualization techniques [including two-dimensional (2D) and 3D representations]. Finally, examples of microscopic retinal structures that are acquired with the University of California Davis AO-OCT system are presented. (c) 2007 Optical Society of America.

[本文引用:1]

[17]

Chen D C, Jones S M, Silva D A, et al. High-resolution adaptive optics scanning laser ophthalmoscope with dual deformable mirrors[J]. 2007, 24( 5): 1305- 1312.

Adaptive optics scanning laser ophthalmoscopes have been used to produce noninvasive views of the human retina. However, the range of aberration compensation has been limited by the choice of deformable mirror technology. We demonstrate that the use of dual deformable mirrors can effectively compensate large aberrations in the human eye while maintaining the quality of the retinal imagery. We verified experimentally that the use of dual deformable mirrors improved the dynamic range for correction of the wavefront aberrations compared with the use of the micro-electro-mechanical-system mirror alone and improved the quality of the wavefront correction compared with the use of the bimorph mirror alone. We also demonstrated that the large-stroke bimorph deformable mirror improved the capability for axial sectioning with the confocal imaging system by providing an easier way to move the focus axially through different layers of the retina.

[本文引用:1]

[18]

Zou W Y, Burns S A. Testing of Lagrange multiplier damped least-squares control algorithm for woofer-tweeter adaptive optics[J]. 2012, 51( 9): 1198- 1208.

A Lagrange multiplier-based damped least-squares control algorithm for woofer-tweeter (W-T) dual deformable-mirror (DM) adaptive optics (AO) is tested with a breadboard system. We show that the algorithm can complementarily command the two DMs to correct wavefront aberrations within a single optimization process: the woofer DM correcting the high-stroke, low-order aberrations, and the tweeter DM correcting the low-stroke, high-order aberrations. The optimal damping factor for a DM is found to be the median of the eigenvalue spectrum of the influence matrix of that DM. Wavefront control accuracy is maximized with the optimized control parameters. For the breadboard system, the residual wavefront error can be controlled to the precision of 0.03 mu m in root mean square. The W-T dual-DM AO has applications in both ophthalmology and astronomy. (C) 2012 Optical Society of America

[本文引用:1]

[19]

Zou W Y, Qi X F, Burns S A. Woofer-tweeter adaptive optics scanning laser ophthalmoscopic imaging based on Lagrange-multiplier damped least-squares algorithm[J]. 2011, 2( 7): 1986- 2004.

We implemented a Lagrange-multiplier (LM)-based damped least-squares (DLS) control algorithm in a woofer-tweeter dual deformable-mirror (DM) adaptive optics scanning laser ophthalmoscope (AOSLO). The algorithm uses data from a single Shack-Hartmann wavefront sensor to simultaneously correct large-amplitude low-order aberrations by a woofer DM and small-amplitude higher-order aberrations by a tweeter DM. We measured the in vivo performance of high resolution retinal imaging with the dual DM AOSLO. We compared the simultaneous LM-based DLS dual DM controller with both single DM controller, and a successive dual DM controller. We evaluated performance using both wavefront (RMS) and image quality metrics including brightness and power spectrum. The simultaneous LM-based dual DM AO can consistently provide near diffraction-limited in vivo routine imaging of human retina. (C) 2011 Optical Society of America

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[20]

Hammer D X, Daniel Ferguson R, Mujat M, et al. Multimodal adaptive optics retinal imager: design and performance[J]. 2012, 29( 12): 2598- 2607.

Optical coherence tomography (OCT) and scanning laser ophthalmoscopy (SLO) are complementary imaging modalities, the combination of which can provide clinicians with a wealth of information to detect retinal diseases, monitor disease progression, or assess new therapies. Adaptive optics (AO) is a tool that enables correction of wavefront distortions from ocular aberrations. We have developed a multimodal adaptive optics system (MAOS) for high-resolution multifunctional use in a variety of research and clinical applications. The system integrates both OCT and SLO imaging channels into an AO beam path. The optics and hardware were designed with specific features for simultaneous SLO/OCT output, for high-fidelity AO correction, for use in humans, primates, and small animals, and for efficient location and orientation of retinal regions of interest. The MAOS system was tested on human subjects and rodents. The design, performance characterization, and initial representative results from the human and animal studies are presented and discussed.

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[21]

Merino D, Loza-Alvarez P. Adaptive optics scanning laser ophthalmoscope imaging: technology update[J]. 2016, 10: 743- 755.

Adaptive optics (AO) retinal imaging has become very popular in the past few years, especially within the ophthalmic research community. Several different retinal techniques, such as fundus imaging cameras or optical coherence tomography systems, have been coupled with AO in order to produce impressive images showing individual cell mosaics over different layers of the in vivo human retina. The combination of AO with scanning laser ophthalmoscopy has been extensively used to generate impressive images of the human retina with unprecedented resolution, showing individual photoreceptor cells, retinal pigment epithelium cells, as well as microscopic capillary vessels, or the nerve fiber layer. Over the past few years, the technique has evolved to develop several different applications not only in the clinic but also in different animal models, thanks to technological developments in the field. These developments have specific applications to different fields of investigation, which are not limited to the study of retinal diseases but also to the understanding of the retinal function and vision science. This review is an attempt to summarize these developments in an understandable and brief manner in order to guide the reader into the possibilities that AO scanning laser ophthalmoscopy offers, as well as its limitations, which should be taken into account when planning on using it.

[本文引用:1]

[22]

Takeno K, Shirai T. Chromatic aberration free liquid crystal adaptive optics for flood illuminated retinal camera[J]. 2012, 285( 12): 2967- 2971.

A high-resolution, flood-illumination retinal camera using liquid crystal (LC) adaptive optics (AO) is presented. The retinal camera uses light at 780 nm for ocular aberration measurement while light at 655 nm and 593 nm for retinal imaging. In order to avoid chromatic aberrations due to wavelength dependence of LC, we adopt an open-loop technique, in which dynamic correction of aberrations is applied only to the imaging light. A compensation pattern projected on the LC wavefront corrector is adjusted to provide phase wrapping of 2 pi for illumination light. We confirmed feasibility of this technique by performing in vivo retinal imaging experiments. Photoreceptors were clearly revealed at both imaging light at 655 nm and 593 nm. Feasibility of the technique was also supported by comparison of the retinal images taken by the present open-loop technique with those taken by the conventional closed-loop one and by analysis of the spatial distribution of the photoreceptors. (C) 2012 Elsevier B.V. All rights reserved.

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[23]

Ooto S, Hangai M, Takayama K, et al. High-resolution imaging of the photoreceptor layer in epiretinal membrane using adaptive optics scanning laser ophthalmoscopy[J]. 2011, 118( 5): 873- 881.

To compare, in eyes with an idiopathic epiretinal membrane (ERM), photoreceptor cell structural abnormalities identified on high-resolution images obtained by adaptive optics scanning laser ophthalmoscopy (AO-SLO) with the severity of metamorphopsia and anatomic findings on spectral-domain optical coherence tomography (SD-OCT). Observational case series. Twenty-five eyes of 24 patients with idiopathic ERM and 20 normal eyes of 20 volunteer subjects. All participants underwent a full ophthalmologic examination, SD-OCT, and imaging with an original prototype AO-SLO system that incorporated liquid crystal-on-silicon technology. In eyes with ERM, M-CHARTS results were used to quantify metamorphopsia. Cone mosaic patterns on AO-SLO images and metamorphopsia severity. In normal eyes, AO-SLO images showed a regular photoreceptor mosaic pattern. In 24 (96%) of 25 eyes with ERM, “microfolds” (multiple thin, straight, hyporeflective lines in the photoreceptor layer) were identified on AO-SLO images; microfolds were not seen in normal eyes. Individual microfolds were approximately 5 to 20 μm wide, which is narrower than retinal folds seen in fundus photographs (>50 μm). Amsler charts revealed metamorphopsia around the fixation point in 12 of 13 eyes with microfolds in the fovea on AO-SLO but in none of 5 eyes without microfolds in the fovea ( P65<650.001). Compared with eyes without foveal microfolds, eyes with foveal microfolds had more severe metamorphopsia (M-CHARTS distortion) in both horizontal and vertical lines ( P65<650.001 for both) and greater average foveal thickness detected by SD-OCT ( P=0.010). Voronoi analysis revealed that smaller numbers of cones in eyes with ERM had 6 neighbors, compared with normal eyes ( P65<650.001). In eyes with ERM, average foveal thickness measured by SD-OCT correlated with visual acuity ( P=0.001) and metamorphopsia scores, both horizontal ( P=0.002) and vertical ( P65<650.001), but visual acuity, metamorphopsia scores, and average foveal thickness were not related to SD-OCT findings of disruption in the photoreceptor inner and outer segment junction. Adaptive optics scanning laser ophthalmoscopy images in eyes with ERM showed abnormal cone mosaic patterns, described as microfolds in the foveal photoreceptor layer. The presence of microfolds was associated with metamorphopsia, suggesting that microfolds may be involved in the formation of metamorphopsia. Proprietary or commercial disclosure may be found after the references.

[本文引用:1]

[24]

Yamaguchi T, Nakazawa N, Bessho K, et al. Adaptive optics fundus camera using a liquid crystal phase modulator[J]. 2008, 15( 3): 173- 180.

We have developed an adaptive optics (AO) fundus camera to obtain high resolution retinal images of eyes. We use a liquid crystal phase modulator to compensate the aberrations of the eye for better resolution and better contrast in the images. The liquid crystal phase modulator has a wider dynamic range to compensate aberrations than most mechanical deformable mirrors and its linear phase generation makes it easy to follow eye movements. The wavefront aberration was measured in real time with a sampling rate of 10 Hz and the closed loop system was operated at around 2 Hz. We developed software tools to align consecutively obtained images. From our experiments with three eyes, the aberrations of normal eyes were reduced to less than 0.1 μm (RMS) in less than three seconds by the liquid crystal phase modulator. We confirmed that this method was adequate for measuring eyes with large aberrations including keratoconic eyes. Finally, using the liquid crystal phase modulator, high resolution images of retinas could be obtained.

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[25]

Li C C, Gong Y, Li J, et al. Optical design of an inducible human eye accommodation fundus camera[J]. Acta Optica Sinica, 2014, 34( 4): 0422001.李春才, 巩岩, 李晶, 等. 可诱导人眼自动调焦的眼底相机光学系统设计[J]. 2014, 34( 4): 0422001.

基于自适应光学设计了一款可诱导人眼自动调焦的眼底相机，包括视度调节系统、照明系统和自适应成像系统。在视度调节系统中，通过设置视标诱导人眼自动调焦，校正人眼初级像差，将人眼残余像差控制在自适应成像系统的校正范围内。在照明系统中，采用轴锥镜组产生环形光照明人眼，消除人眼角膜的强反射光，通过调节轴锥镜之间的距离使环形光束内径连续变化以适应不同的人眼。在自适应成像系统中，使用哈特曼夏克波前传感器作为波前探测器，使用变形镜作为波前校正器，校正人眼的高阶像差。仿真结果表明，眼底照明均匀度可达95%，自适应成像系统在截止频率76 lp/mm处，各视场调制传递函数(MTF)值均大于0.36。系统畸变小于1%，能够对在-6D～+8D(D表示屈光度数)之间的人眼眼底清晰成像。

[本文引用:1]

[26]

van Norren D, Tiemeijer L F. Spectral reflectance of the human eye[J]. 1986, 26( 2): 313- 320. 101016/0042-6989(86)90028-3

Spectral reflectance of the eye was assessed in four young Caucasian subjects with the Utrecht densitometer. Three retinal locations were studied, the fovea, the optic disk and a spot 12 deg temporal on the horizontal meridian. Reflectance was measured with the visual pigments bleached away. The measuring field subtended 2.5 deg. The reflectance factor, relative to an artificial eye with a focal distance of 21.3 mm, was found to be lowest in the blue (0.1% for 419 nm) and highest in the red (10% for 711 nm). A model with six parameters, four densities of (non-photolabile) ocular pigments and two reflectance factors, was proposed to explain the experimental findings. A good fit to the data was obtained and the calculated densities of the ocular pigments came close to data found in the literature.

[本文引用:1]

[27]

Kong N N, Li C, Xia M L, et al. Research on flat field correction method in adaptive optics retinal imaging system[J]. Acta Optica Sinica, 2011, 31( 12): 1211001.孔宁宁, 李抄, 夏明亮 等. 用于自适应光学视网膜成像的平场校正方法研究[J]. 2011, 31( 12): 1211001.

采取平场校正的方法消除薄型背照式电荷耦合器件(CCD)相机在对视网膜细胞成像时由于多光束干涉效应在输出图像上产生了干涉条纹。在分析CCD芯片多光束干涉效应产生机理的基础上，根据视网膜细胞成像的特点，提出将未进行像差补偿的视网膜图像作为平场校正的参考图像对像差补偿之后的图像进行校正，解决了标准反射率白板图像作为平场校正参考图像时残留有干涉条纹的问题。通过计算平场校正前后视网膜细胞图像的平均功率谱验证消除干涉条纹的效果，在空间频率70~90 lp/(°)范围内，校正之后图像的功率谱的平均值比校正之前提高了132.1%。实验结果表明，利用未进行像差补偿的眼底图像作为平场校正参考图像可以有效地消除视网膜细胞图像上的干涉条纹，提高视觉细胞的对比度，所获得的图像质量有了明显的改善。

[本文引用:1]

[28]

Atchison D A, Lucas S D, Ashman R, et al. Refraction and aberration across the horizontal central 10 of the visual field[J]. 2006, 83( 4): 213- 221.

Abstract PURPOSE: The purpose of this study was to measure refraction and aberrations across the horizontal central visual field. METHODS: Cycloplegic refraction was measured on eight subjects at 13 points across the horizontal central 10 degrees of the retina using a Hartmann-Shack wavefront sensor. Refractions were converted into mean sphere (M), 90 degrees to 180 degrees astigmatism (J180), and 45 degrees to 135 degrees astigmatism (J45) components. For five subjects, higher-order aberrations were determined at the center and edges of the field. RESULTS: Subtle changes in refraction were found to exist across the central 10 degrees of the retina, with changes in mean best sphere varying by up to half a diopter across this region and with smaller changes in astigmatism. Horizontal coma, but no other higher-order aberrations, varied systemically across the visual field; it varied linearly with angle but at different rates for the different subjects. CONCLUSION: Subtle changes in cycloplegic refraction exist across the horizontal central 10 degrees of the retina. The results indicate the need for correct alignment when measuring objective refraction.

[本文引用:1]

[29]

Lasland es M, Salas M, Hitzenberger C K, et al. Increasing the field of view of adaptive optics scanning laser ophthalmoscopy[J]. 2017, 8( 11): 4811- 4826.

An adaptive optics scanning laser ophthalmoscope (AO-SLO) set-up with two deformable mirrors (DM) is presented. It allows high resolution imaging of the retina on a 4°×4° field of view (FoV), considering a 7 mm pupil diameter at the entrance of the eye. Imaging on such a FoV, which is larger compared to classical AO-SLO instruments, is allowed by the use of the two DMs. The first DM is located in a plane that is conjugated to the pupil of the eye and corrects for aberrations that are constant in the FoV. The second DM is conjugated to a plane that is located 650.7 mm anterior to the retina. This DM corrects for anisoplanatism effects within the FoV. The control of the DMs is performed by combining the classical AO technique, using a Shack-Hartmann wave-front sensor, and sensorless AO, which uses a criterion characterizing the image quality. The retinas of four healthy volunteers were imaged in-vivo with the developed instrument. In order to assess the performance of the set-up and to demonstrate the benefits of the 2 DM configuration, the acquired images were compared with images taken in conventional conditions, on a smaller FoV and with only one DM. Moreover, an image of a larger patch of the retina was obtained by stitching of 9 images acquired with a 4°×4° FoV, resulting in a total FoV of 10°×10°. Finally, different retinal layers were imaged by shifting the focal plane.

[本文引用:1]

[30]

Sulai Y N, Dubra A. Adaptive optics scanning ophthalmoscopy with annular pupils[J]. 2012, 3( 7): 1647- 1661.

Annular apodization of the illumination and/or imaging pupils of an adaptive optics scanning light ophthalmoscope (AOSLO) for improving transverse resolution was evaluated using three different normalized inner radii (0.26, 0.39 and 0.52). In vivo imaging of the human photoreceptor mosaic at 0.5 and 10 from fixation indicates that the use of an annular illumination pupil and a circular imaging pupil provides the most benefit of all configurations when using a one Airy disk diameter pinhole, in agreement with the paraxial confocal microscopy theory. Annular illumination pupils with 0.26 and 0.39 normalized inner radii performed best in terms of the narrowing of the autocorrelation central lobe (between 7 and 12%), and the increase in manual and automated photoreceptor counts (8 to 20% more cones and 11 to 29% more rods). It was observed that the use of annular pupils with large inner radii can result in multi-modal cone photoreceptor intensity profiles. The effect of the annular masks on the average photoreceptor intensity is consistent with the Stiles-Crawford effect (SCE). This indicates that combinations of images of the same photoreceptors with different apodization configurations and/or annular masks can be used to distinguish cones from rods, even when the former have complex multi-modal intensity profiles. In addition to narrowing the point spread function transversally, the use of annular apodizing masks also elongates it axially, a fact that can be used for extending the depth of focus of techniques such as adaptive optics optical coherence tomography (AOOCT). Finally, the positive results from this work suggest that annular pupil apodization could be used in refractive or catadioptric adaptive optics ophthalmoscopes to mitigate undesired back-reflections. (C) 2012 Optical Society of America

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Jiang H L, Liao N, Li C H, et al. High-speed compact adaptive optics scanning laser ophthalmoscope[J]. Acta Optica Sinica, 2015, 35( 11): 1117002.江慧绿, 廖娜, 李超宏 等. 高帧频紧凑型自适应光学扫描激光检眼镜[J]. 2015, 35( 11): 1117002.

基于自适应光学(AO)像差校正技术的激光共聚焦扫描检眼镜是当前研究的热点，为眼底疾病早期诊断提供有力的支持。利用可连续变形镜和夏克-哈特曼探测器为核心器件搭建了一套高帧频紧凑型自适应光学扫描激光检眼镜(AOSLO)系统，系统物理尺寸为350 mm×400 mm，图像采集帧频为40 fps，分别进行了系统分辨率测试与人眼视网膜成像初步实验。结果表明，系统人眼视网膜面上的分辨率可达到2.50 μm，达到极限分辨率(2.32 μm)，可实现细胞量级高分辨率成像，自适应光学系统能够校正人眼像差，校正前后图像质量有明显的提高，能清楚地观察到人眼视网膜视盘附近的血管以及黄斑区细胞图像。

[本文引用:1]

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... 由于人眼是一个动态变化的、不完善的光学系统[5],而现有的常规眼底成像设备[6,7]只能校正静态像差,其分辨率(10~15 μm[8])无法满足对疾病早期微小病变检测的要求 ...

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... 由于人眼是一个动态变化的、不完善的光学系统[5],而现有的常规眼底成像设备[6,7]只能校正静态像差,其分辨率(10~15 μm[8])无法满足对疾病早期微小病变检测的要求 ...

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... 2002年Roorda等[13]首次将AO技术与共焦扫描激光检眼镜结合搭建了实验系统,极大地提高了系统的横向、纵向成像分辨率,获得了视细胞、毛细血管血流等高分辨率图像 ...

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... 2) 采用双变形镜(dual-DM)校正人眼低阶像差和高阶像差[16,17,18,19,20],利用大行程变形镜校正低阶像差,利用小行程高精度的变形镜校正高阶像差,其缺点是成本大,低阶像差校正范围有限(±3 m-1屈光度),不利于产品化等,如Chen等[17]采用双变形镜校正人眼像差,35单元Bimorph变形镜校正人眼低阶像差,144单元微机电(MEMS)变形镜校正人眼高阶像差,Zou等[18,19]采用超大行程的Mirao变形镜校正人眼低阶像差,140单元MEMS变形镜校正人眼高阶像差 ...

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... 3) 反射离轴系统,由于考虑到摆放空间,反射元件需要有一定的离轴角度,从而引入系统像散[21] ...

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... 入瞳:对于成像光路,采用人眼瞳孔作为AOSLO系统的入瞳,正常情况下人眼瞳孔直径为2~8 mm[25],考虑到系统分辨率,尽量取较大的瞳孔作为系统入瞳,再结合变形镜通光口径,这里取入瞳直径为6 ...

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... 为保证系统成像质量达到最佳,尽量选用波长较短、视网膜反射率较高[26]、眼睛舒适、宽带宽激光光源 ...

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... 为避免影响图像质量尽量消除相干光引起的斑点[27] ...

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... 据报道,瞳孔直径为6 mm,其等晕角约为2°(圆)[28],而瞳孔直径为4~6 mm,其等晕角则小于2 ...

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... 5°[29],这里取2 ...

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... 1 mm[30],采用焦距为17 ...

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... 11 μm)[31] ...