CN102939044A - 用于表征角膜并制造眼用透镜的系统 - Google Patents

用于表征角膜并制造眼用透镜的系统 Download PDF

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CN102939044A
CN102939044A CN201080018948XA CN201080018948A CN102939044A CN 102939044 A CN102939044 A CN 102939044A CN 201080018948X A CN201080018948X A CN 201080018948XA CN 201080018948 A CN201080018948 A CN 201080018948A CN 102939044 A CN102939044 A CN 102939044A
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cornea
fluorescence
front surface
interior zone
rear surface
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CN102939044B (zh
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J·F·比勒
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Perfect Lance Ltd.
Perfect IP LLC
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Aaren Scientific Inc
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    • A61F2/00Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
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    • A61B3/107Objective types, i.e. instruments for examining the eyes independent of the patients' perceptions or reactions for determining the shape or measuring the curvature of the cornea
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    • BPERFORMING OPERATIONS; TRANSPORTING
    • B23MACHINE TOOLS; METAL-WORKING NOT OTHERWISE PROVIDED FOR
    • B23KSOLDERING OR UNSOLDERING; WELDING; CLADDING OR PLATING BY SOLDERING OR WELDING; CUTTING BY APPLYING HEAT LOCALLY, e.g. FLAME CUTTING; WORKING BY LASER BEAM
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    • B23K26/02Positioning or observing the workpiece, e.g. with respect to the point of impact; Aligning, aiming or focusing the laser beam
    • B23K26/06Shaping the laser beam, e.g. by masks or multi-focusing
    • B23K26/062Shaping the laser beam, e.g. by masks or multi-focusing by direct control of the laser beam
    • B23K26/0626Energy control of the laser beam
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B23MACHINE TOOLS; METAL-WORKING NOT OTHERWISE PROVIDED FOR
    • B23KSOLDERING OR UNSOLDERING; WELDING; CLADDING OR PLATING BY SOLDERING OR WELDING; CUTTING BY APPLYING HEAT LOCALLY, e.g. FLAME CUTTING; WORKING BY LASER BEAM
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    • B23K26/36Removing material
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B23MACHINE TOOLS; METAL-WORKING NOT OTHERWISE PROVIDED FOR
    • B23KSOLDERING OR UNSOLDERING; WELDING; CLADDING OR PLATING BY SOLDERING OR WELDING; CUTTING BY APPLYING HEAT LOCALLY, e.g. FLAME CUTTING; WORKING BY LASER BEAM
    • B23K26/00Working by laser beam, e.g. welding, cutting or boring
    • B23K26/36Removing material
    • B23K26/361Removing material for deburring or mechanical trimming
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    • B29WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29DPRODUCING PARTICULAR ARTICLES FROM PLASTICS OR FROM SUBSTANCES IN A PLASTIC STATE
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    • B29D11/00009Production of simple or compound lenses
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    • BPERFORMING OPERATIONS; TRANSPORTING
    • B29WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29DPRODUCING PARTICULAR ARTICLES FROM PLASTICS OR FROM SUBSTANCES IN A PLASTIC STATE
    • B29D11/00Producing optical elements, e.g. lenses or prisms
    • B29D11/02Artificial eyes from organic plastic material
    • B29D11/023Implants for natural eyes
    • GPHYSICS
    • G02OPTICS
    • G02CSPECTACLES; SUNGLASSES OR GOGGLES INSOFAR AS THEY HAVE THE SAME FEATURES AS SPECTACLES; CONTACT LENSES
    • G02C7/00Optical parts
    • G02C7/02Lenses; Lens systems ; Methods of designing lenses
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    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B2576/00Medical imaging apparatus involving image processing or analysis
    • A61B2576/02Medical imaging apparatus involving image processing or analysis specially adapted for a particular organ or body part
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    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
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    • A61F2/14Eye parts, e.g. lenses, corneal implants; Implanting instruments specially adapted therefor; Artificial eyes
    • A61F2/145Corneal inlays, onlays, or lenses for refractive correction
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
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Abstract

本发明公开了一种用于测定眼睛角膜形状的系统,用具有能使被照射的角膜部分产生荧光的波长的红外光照射眼睛的前表面、后表面和内部区域中的至少一个。随后检测产生的荧光。其照射步骤包括在与眼睛光轴基本垂直的多个不同的平面上聚焦红外光。根据检测到的光线可以制作角膜的至少一部分前表面、至少一部分后表面和/或一部分内部区域的地形图。通过使视网膜的色素上皮细胞中的蛋白产生自发荧光可确定视力的清晰度。

Description

用于表征角膜并制造眼用透镜的系统
交叉申请
本申请请求了以下美国临时申请的权益:2009年3月4日提交的61/209,362、2009年3月4日提交的61/209,363、2009年5月27日提交的61/181,420、2009年5月27日提交的61/181,519以及2009年5月27日提交的61/181,525。这些美国临时申请均在此通过引用而构成本文的一部分。但是,下面的描述与这些临时申请的公开内容不一致时,以下面的描述为准。
背景技术
已知多种用于表征角膜的系统,并利用表征的信息来制作眼用透镜。参见,例如美国专利号6413276、6511180、6626535和7241311。
已知用于表征角膜的系统的难点在于人角膜的特性会受到测量时存在的水分含量的影响。因而,例如,为一名患者制作眼用透镜时,如果表征的是患者干燥眼环境下的患者的角膜,那么当患者眼睛含有大量水分时这个透镜将不适合患者。
常规系统的另一个问题是通常没有考虑角膜的内部结构。我们认为角膜的聚焦效应是通过角膜的前表面、角膜的后表面和角膜的内部结构共同实现的,分别发挥了大约80%,10%,和10%的作用。没有考虑角膜的内部结构的做法,以及在一些情况下没有考虑角膜后表面的形状的做法,将得到无法提供令人满意的视力的透镜。
因此,需要提供一种改良的用于表征角膜的系统,目的是制得可置入人眼的眼用透镜。更理想的是,该系统可以分析放置好的透镜在视网膜上聚焦光的有效性。
本发明还包括一种用于测定患者视力清晰度的系统,以确定植入透镜或其他供给患者的眼用修正物的有效性。依据本方法,用能在视网膜上产生荧光的波长的扫描光线照射患者眼睛,用诸如光检测器检测荧光产生的图像的清晰度。荧光由视网膜的色素上皮细胞中的蛋白质以及视网膜的感光体产生。
随后,调整扫描光线的路径长度,以增大荧光产生的图像的清晰度。扫描光线通常的波长是750至大约800nm,优选为大约780nm。
发明内容
本发明提供了一种符合所述需求的系统。该系统包括一种用于测定眼睛角膜形状的方法和设备,其中,角膜具有一个前表面、一个后表面以及一个位于前和后表面之间的内部区域。本方法依赖于角膜产生的荧光,与采用入射光的反射系数来确定角膜形状的现有技术不同。依据该方法,用具有可使被照射的角膜部分产生荧光的波长的红外光照射角膜的前表面、后表面和内部区域中的至少一个。检测产生的荧光。用检测到的荧光来制作角膜的前表面、后表面和/或内部区域的形状图。“前表面”指的是眼睛朝外的表面。“后表面”向后朝向视网膜。
例如,在角膜的前部区域的例子中,测定内部区域中多个位置的光路长度。内部区域产生的蓝光的存在指出了角膜内胶原蛋白薄层的存在。
优选地,照射的步骤包括在与眼睛的光轴基本垂直的多个不同的平面上聚焦红外光。这些平面可与角膜的前表面、角膜的后表面和/或角膜的内部区域相交错。
本发明还包括实施该方法的设备。优选的设备包括激光器、聚焦装置和检测器,激光器将具有能够使被照射的角膜部分产生荧光的波长的红外光照射角膜的选定部分;聚焦装置如聚焦透镜,在角膜的选定部分上聚焦光线;以及检测器如光电二极管检测器,检测产生的荧光。
本发明还包括一种用于测定患者视力清晰度的系统,以确定植入透镜或其他供给患者的眼用修正物的效用。依据该方法,用具有能使视网膜上产生荧光的波长的扫描光线照射患者眼睛,以及用诸如光检测器检测荧光产生的图像的清晰度。荧光由视网膜的色素上皮细胞中的蛋白以及视网膜的感光体产生。随后,调整扫描光线的路径长度,以增大荧光产生的图像的清晰度。入射光通常的波长是750至大约800nm,优选为大约780nm。词语“视力清晰度”指的是受试者辨别亮度不同的两个图像(白色为100%亮度,黑色为0%亮度)的能力。受试者能察觉不同的两个图像的对比差别(相对亮度)越小,受试者的视力清晰度越高。
附图说明
结合下面的描述、附录的权利要求以及附图将能更好理解本发明的这些和其他特征、各个方面和优点,其中:
图1是用于人工晶状体眼的本发明的方法的示意图;
图2是人眼和激光视力矫正手术后的眼睛的晶状体存在的球面像差的图解表示;
图3是确定视网膜图像清晰度的一种计算方式的示意图;
图4是可用于确定视力清晰度的计算方法中的卷积的数学程序的直观图;
图5是示出作为有限元建模(FEM)结果的负载角膜中的应力应变分布的侧横截面图;
图6是显示二次谐波成像(SHGi)和双光子激发荧光成像(TPEFi)的物理过程的示意图;
图7示意性地显示了可用于本发明的双光子显微镜/检眼镜的主要部件;
图8是胶原组织结构的SHGi的概览图;
图9示出了角膜的微形态计量特征;
图10示出了在类似定制的眼内透镜(C-IPSM)的尺寸的视野上制作合成角膜形状图的示意图;以及
图11是用于检测由植入眼内的透镜获得的图像清晰度的系统的示意图。
具体实施方式
概述
一种用于确定角膜地形图(包括角膜的前和后表面以及内部区域的地形图)的系统,包括测定和模拟步骤,提供角膜内折射率分布的值。可采用角膜内应力/应变关系的有限元建模的统计分布和结果。
本发明使用的设备可以是双光子显微镜,以获得多个高空间分辨率的测量结果。设备采用的每个单独的光束具有唯一的光路长度。可采用二次谐波成像(SHGi)和双光子激发荧光成像(TPEFi)的方法。利用这些测量产生的多个象素数据,可以评估角膜的折射特性的详细的空间分布,因此可制作能精确补偿检测到的像差的眼内透镜。
该系统还包括用于测定眼内透镜有效性的方法,比如,质量控制方法。
表征角膜
首先参看图1,其示意性地示出了用于测定植入的透镜如定制的眼内透镜的折射特性的系统,并将其标注为10。多个光束40传播穿过植入定制的眼内透镜20内的人工晶状体眼,该透镜可以高空间分辨率并局部校正每个光束的光路长度。这些光线被引导通过所述人工晶状体眼,在视网膜30上形成图像。多个单独的光束40的特征是每个光束具有唯一的光路长度。更具体地,每个光路长度表示每个光束在传播通过眼睛期间其所经历的折射。接下来,用计算机收集全部光路长度,创建眼睛的视网膜上的数字化图像。多个光束40按顺序传播通过角膜14的前表面12、角膜14的内部区域13、角膜14的后表面16以及具有前表面层22的定制的眼内透镜,并在视网膜30上形成聚焦图像。在同天提交的申请号为12/717,886、题为“制作和调节透镜的系统和由此制得的透镜”(案卷19780-1)的申请人的共同申请中记载了制作透镜20的方法,该文献在此通过引入构成本文的一部分。
在多个光束40的上部,示出了三个相邻光束42,44,和46,代表了分区方法中的一个局部区域。通常来说,在高空间分辨率的光线追踪计算中,要根据它们在人眼中的光学路径长度来评估数以千万的光线。出于计算的目的,选定一个接近人工晶状体眼的天然瞳孔的基准面18,由此标准化单个光束的光学路径长度。更具体地,单个光线从瞳孔平面18至定制的眼内透镜20的前面表22的传播可表示为exp(ix(2π/λ)xn(x,y)xz(x,y)),其中exp类似于指数函数,i表示虚数单元数目,π等于大约3.14,λ表示光线的波长,n(x,y)表示局部折射率,z(x,y)表示坐标为x和y的横向位置距离瞳孔平面18的实际距离。可以用实际长度z(x,y)的值来表达定制的眼内透镜(C-IPSM)20在透镜植入期间出现的与轴向或横向位置或倾斜相关的定位的任意错误,也可用光学技术通过体内微调表层22来对此类错误进行补偿,该种光学技术例如是在上述同天提交的申请号为12/717,886、题为“制作和调节透镜的系统和由此制得的透镜”(案卷19780-1)的申请人的共同申请中所述的,该文献在此通过引入作为本文的一部分。
图2显示了在正常眼睛(如晶状体)和激光原位角膜磨镶术后的眼睛(如经整形的角膜)中存在的人眼的一种特殊的光学像差,如球面像差,显示了激光原位角膜磨镶术后的眼睛60中的球面像差的感应。在图2的上部分中,举例显示了正常眼睛50的情况。眼球52包含角膜56、透镜54和视网膜58。通常,对于6mm的瞳孔直径,引入对应0.5μm的大约一个波长λ的球面像差59,其主要与晶状体的球面形状相关。在图2的下部分,在经历了近视矫正手术后的眼睛60的情况中,图示了大量的球面像差的引入。眼球62具有角膜66、透镜64和视网膜68。通常会遇到对应5μm 的大约10个波长λ(10λ)的球面像差,其主要与中央扁平的角膜的边缘相关。
图3是确定植入的透镜的必需的折射效果的计算途径70的示意图。多种光束72转换成一个瞳孔函数74,可被想象为路径长度76的空间分布,并可以用数学式78表达:P(x,y)=P(x,y)exp(ikW(x,y)),其中P(x,y)是振幅,exp(ikW(x,y))是合成瞳孔函数的相位。相位取决于波矢量k=2πr/λ,λ是单个光束的波长,W(x,y)是其路径长度, i表示虚数单元数目。点扩展函数(PSF)80可自瞳孔函数74导出,数学上可表达为傅里叶变换82:PSF(x,y)=|FT(P(x,y))|2,还可图解地表示为伪三维函数84,显示接近衍射受限的情况,示出人工晶状体眼仅具有较小的光学像差。斯特列尔比i 86可从计算式70中根据88:i=(max(PSF(x,y))/max(PSFdiff(x,y))导出,其中PSF(x,y)表示有像差的光学系统的点扩展函数,PSFdiff(x,y)类似于理想化的衍射受限的光学系统。点扩展函数(PSF)80和斯特列尔比i 86可用于直观化眼睛的光学性能和视网膜图像的清晰度。
图4是可用于评测视网膜图像清晰度的卷积计算的数学过程的直观图。成像过程90可直观化为称为卷积94的数学运算过程,其中通过卷绕每个图像点与光学系统的点扩展函数PSF96,可模糊化物体92的理想化图像,得到图像100。在具有6mm瞳孔直径的人眼的情况中,PSF96显示为伪三维图98。因而,视网膜图像100的清晰度可由点扩展函数PSF96确认。
图5是示出作为有限元建模(FEM)结果的负载角膜中的应力和应变分布的侧横截面图。用有限元建模(FEM)算法102模拟负载角膜上的应力104和应变106的分布,可以测定角膜内部基质组织的局部密度,可自这个密度导出折射率的空间分布n(x,y),得到角膜内多种光束的光学路径长度的可变性的测量结果。首先,有限元建模(FEM)提供了与局部组织密度成比例的体积单元中的刚度参数的分布。例如在A.Pandolfϊ等人的Biomechan. Model Mechanobiology 5237-246,2006中描述了FEM建模在角膜生物力学中的应用。同样在后表面上施加2千帕 (kPA) (15mmHg)的眼内压力。仅前弹性层108完整固定在边缘上。在图5的左边部分上,示出了沿着径向方向的柯西应力分布;绝对值的范围是-2.5kPa至+2.5kPa。在图5的右边部分上,显示了最大主应变分布;基质组织的相对压缩或膨胀介于-0.07至+0.07之间。
用荧光发射法表征角膜
图6是显示二次谐波成像(SHGi)和双光子激发荧光成像(TPEFi)的物理过程的示意图。在图6的上部左侧,示出了二次谐波成像(SHGi)140的原理。连贯地添加频率为ωp的双光子146和148,产生瞬时从能级144再辐射至142的具有频率2ωp的光子150。在图6的上部右侧,直观化了双光子激发荧光成像(TPEFi)过程。频率我饿ωp的双光子156和158将分子从基态能级152激发至激发能级154。由于分子在大约1毫微秒内被去激励至能级162,因此在大约1微微秒内经热辐射至能级160后,荧光光子ωF再次辐射。在图6的下部分中,例示出了SHGi(二次谐波发生)和TPEFi(双光子激发荧光)的成像过程的波长依赖性。通常,由于频率为ωp的照射飞秒激光束的波长从166经168降至170,频率为2ωp的SHGi信号174,176和178的强度以及频率为ωF的TPEFi信号182、184和186的强度增大。在双光子角膜显微镜/检眼镜中,如图7所述的,使用波长为780nm的照射飞秒激光,以优化角膜内部胶原纤维和细胞突的成像的对照。
图7示意性示出用于表征角膜设计而定制的眼内透镜的优选的设备702。设备702包括激光器704,优选双光子激光器;控制单元706和扫描单元708。双光子激发显微镜是一种荧光成像技术,能够成像存活组织至1毫米的深度。双光子激发显微镜是多光子荧光显微镜的一种特殊的型号。双光子激发由于其较深的组织深入性、有效的光检测和较小的射线损害而优于共焦显微镜检查法。双光子激发的概念基础是低能的双光子可以在一个量子级别中激发的荧光团,导致荧光光子通常以比两个激发光子中的任一个更高的能量发射出。双光子的近同时吸收的概率非常低。因此,通常需要高通量的激发光子,常常是飞秒激光。
适宜的激光器可来自美国加州桑尼维尔CalmarLaser公司。该激光器发出的每个脉冲的持续时间是大约50至大约100飞秒,能级至少是大约0.2nJ。优选地,激光器704在每秒内产生大约5千万个波长为780nm的脉冲,脉冲长度是大约50fs,每个脉冲的脉冲能量是大约10nJ,激光器是500mW激光器。发出的激光束720由转向镜722引导穿过中性滤光片724以选择脉冲能量。激光器发出的激光束720的直径通常是大约2mm。随后,激光束720穿过分色镜728,然后到达扫描单元708,扫描单元708将脉冲在空间上分布成多种形式的光束。计算机控制系统730控制扫描单元708,扫描眼中的角膜732。
激光器发出的光束720的直径是大约是2至2.5mm。离开扫描仪708的光束720随后由聚焦装置聚焦成适合扫描角膜732的尺寸,通常是直径为大约1至2μm的光束。聚焦装置可以是任意系列的可用来减小激光束至理想尺寸的透镜和光学设备,如棱镜。聚焦装置可以是伸缩透镜对742和744以及显微镜物镜746,其中第二转向镜748引导光束从透镜对到达显微镜物镜。聚焦显微镜物镜可以是40x/0.8的工作距离为3.3mm的物镜。扫描和控制单元优选为位于德国海德堡的Heidelberg Engineering公司的Heidelberg Spectralis HRA扫描单元。
扫描单元中的光学器件中具有一块直径为大约150至450μm的无需移动角膜732或光学装置即可扫描到的区域。为了扫描角膜的其他区域,必须在x,y平面上移动角膜。同时,为了扫描角膜的不同深度,必须在z方向上移动激光扫描仪的焦点平面。
控制单元706可以是任意计算机,包括存储器、处理器、显示器和输入装置,如鼠标和/或键盘。控制单元已编好程序,使来自扫描单元708的激光束具有需要的模式。
角膜732前表面上的细胞在780nm的激光束的激发下将发出荧光,产生大约530nm波长的绿光。发出的光沿着入射激光的路径前进,即,入射光穿过显微镜物镜746,被转向镜748反射通过透镜744和742,穿过扫描单元708进入分色镜728,分色镜将荧光反射至路径780,通常与穿过分色镜728的入射光的路径成直角。在路径780中,发出的光穿过滤光器782,滤除具有不需要的频率的光,随后通过聚焦透镜784到达光检测器786。光检测器可以是雪崩光电二极管。光检测器得到的数据可存储在计算机控制单元730的存储器或其他存储器中。
因而,用具有能产生荧光的波长的红外光照射角膜的前表面,检测产生的荧光。对前表面来说,入射红外光聚焦在基本与眼睛光轴相垂直的多个不同的平面上,其中这些平面与角膜的前表面相交错。
可用相同的步骤来表征后表面,在基本与眼睛光轴相垂直的多个不同的平面上聚焦红外光,其中这些平面与角膜的前表面相交错。在64个分离的平面上进行扫描,其中用间隔大约为3微米的光束进行扫描。
扫描角膜内部的区别在于内部区域中的胶原蛋白薄层产生的是蓝光而非绿光。蓝光的波长大约为390nm。当扫描角膜内部时,必须使用另一个滤光器732来确认蓝光均穿过滤光器到达光检测器786。
图8是胶原组织结构的SHG成像的概览图。在图8的上部左侧直观化了胶原三螺旋188,示出了胶原纤维的典型结构。胶原纤维是位于角膜基质内部的合成的三维层状结构的有机体。在图8的下部左侧中,示出了二次谐波发生(SHG)激光/胶原纤维相互作用的过程。频率为ω的光子194使较远纤维偏振至中间能级196,然而,相同频率ω的第二光子198也产生了瞬间的电子能级192。电子激发立即被再辐射成双倍能量的光子200,频率为2ω。由于胶原纤维的单向形状,使得这个过程能获得较高的产率。近来已经报道了角膜组织的二次谐波成像(SHGi)(M.Han,G.Giese,和J.F.Bille,“角膜和巩膜中的胶原纤维的二次谐波成像”,Opt.Express13,5791-5795(2005))。用图7的设备进行测量。根据开自胶原纤维的非线性光学偏振226的方程式224测定SHGi信号。信号强度228与二阶偏振项[χ(2))]2直接成正例,与飞秒激光脉冲的脉冲长度π成反比。这样,如图7所述的,由于胶原纤维的强单向性以及双光子角膜显微镜/检眼镜内使用的飞秒激光的超短脉冲长度,高对比度的SHGi图像直观地显示了角膜基质的三维层状结构。
在解剖学上,图9示出了眼睛的角膜14,从其前表面12至其后表面16包括上皮230,前弹性层244、基质246,后弹性层248,和内皮250。上皮230由多个细胞层组成,如并入基细胞层242中的细胞层232、234、236、238和240。双光子角膜显微镜的双光子激发自发荧光模式(TPEF)可清晰成像基细胞层242以及前表面12,可以得到上皮230的厚度的空间分辨的测量结果。还可用双光子角膜显微镜的双光子激发自发荧光模式成像内皮,得到角膜14的厚度的空间分辨的测量结果。基质246由接近200个胶原蛋白薄层组成,如252、254、256、258、260、262和264,具有合成的三维结构,可利用双光子角膜显微镜的二次谐波成像(SHGi)模式评估。基于这些测量结果,如图5所例举的,在胶原结构刚度的有限元建模(FEM)的支持下,可以重构角膜内部的折射率的三维分布。因而,可以高空间分辨率测定光线追踪计算中多个光束在角膜内部的光学路径长度。因而,可以绘制角膜的前表面、后表面和/或内部结构的地形图。
在图10中,示出了由多个单体成像区域形成的合成角膜形状图270。通常,中央成像区域280延伸超出大约2mm的直径,包括接近2000x2000个成像像素,总计4百万成像点或像素,得到接近1μm的分辨率(如使用尼康50x/0.45显微镜物镜)。合成的角膜形状图270包含双光子显微镜图像的三维堆叠,由双光子激发荧光成像(TPEFi)或二次谐波成像(SHGi)-成像模型组成。为了匹配直径接近6mm的定制的眼内透镜的尺寸,采用了6个外围的成像区域290、292、294、296、298和300。利用交叠区310、312、314、316、318和320中的运行时间的灰度值象素的交叉相关算法实现单体区域的定位。因而,合成角膜地形图具有接近2千8百万个数据,提供了穿过角膜的一个横向薄片的空间分辨的合成图像。通常,用穿过角膜的一百个横向薄片来重构当多个光束通过人工晶状体眼的角膜时所述光束的光路长度。
设计和制作透镜
根据图7的设备获得的数据设计透镜的方法在现有技术中是公知的,包括了Roffman提出的美国专利5,050,981中所记载的方法,对于这些方法该文献在此通过引入作为本发明的一部分。在申请人前述的共同申请的美国专利12/717,886(案卷19780-1)中也描述了制作或调整透镜的方法。
视力清晰度的测定
参看图11,其示意性地说明了一种用于测定患者的视力清晰度的系统,在图11的例子中,还具有植入的眼内透镜1102。用于此的系统基本与图7示出的设备相同,使用了相同的激光器704和扫描仪708。任选地,出于模拟与图像清晰度和焦距深度相关的折射校正效应的目的还可使用自适应光学模块(AO模块)1104。出于预补偿激光器704产生的单个光束的目的,AO模块708由相位板补偿器和活动镜组成。在申请人的美国专利7,611,244中描述了可用于本发明的用来补偿光束中的不对称像差的自适应装置。在申请人的美国专利6,155,684中描述了用自适应光学反馈控制预补偿人的折射特性的方法和设备。在申请人的美国专利号6,220,707中描述了活动反射镜的使用。单个光束1112穿过角膜1114,随后是眼内透镜1102,聚焦在视网膜上,形成视网膜图像1120。由于进入的光的波长是大约750至大约800nm,优选地为大约780nm,色素上皮细胞中的荧光蛋白和感光体将发出频率为大约530nm至大约550nm的荧光。图11用线1122示出了发出的光。发出的荧光的强度表明了角膜1114和眼内透镜1102聚焦进入的光束的情况,并找出其中的对应关系,其中更高的强度示出更好的聚焦。为了测定是否获得改善了的聚焦,为了增大荧光产生的图像的清晰度,可以诸如通过调整自适应光学模块1104中的相位板或活动反射镜改变进入的扫描光的路径长度。
任选地,可提供视力刺激1124,如斯内伦视力表,获得患者在视力清晰度方面的客观的反馈。
利用该方法,可以测定植入透镜,如人工晶体(IOL)、角膜透镜或接触透镜,以及原位置透镜的变型(角膜、IOL和天然晶状体透镜)的效力。
虽然优选的实施方式已经在细节上描述了本发明,但也可能存在其它的实施方式。例如,虽然是对应眼内透镜的用途来描述本发明,但可以理解获得的用于表征角膜的数据也可用于制作接触透镜和其它植入眼睛的透镜。因此,本发明的权利要求所保护的范围不应受到这里所包含的对优选实施方式的描述的限制。

Claims (34)

1.一种测定眼睛角膜形状的方法,所述角膜具有前表面、后表面和位于所述前表面和后表面之间的内部区域,本方法包括以下步骤:
a)用具有能使被照射的角膜部分产生荧光的波长的红外光照射所述前表面、后表面和内部区域中的至少一个;以及
b)检测产生的荧光。
2.根据权利要求1所述的方法,其中步骤a)包括照射所述前表面。
3.根据权利要求1所述的方法,其中照射步骤a)包括照射所述后表面。
4.根据权利要求1所述的方法,其中照射步骤a)包括照射所述内部区域。
5.根据权利要求4所述的方法,还包括一个测定所述内部区域中多个位置的光路长度的额外步骤。
6.根据权利要求5所述的方法,其中测定患者角膜内部的多个地点的光路长度包括检测任何产生的蓝光,其中蓝光的存在表明了角膜中胶原蛋白薄层的存在。
7.根据权利要求6所述的方法,其中所述蓝光的波长大约为390纳米。
8.根据权利要求1所述的方法,其中照射步骤a)包括照射所述前表面、后表面和内部区域。
9.根据权利要求1所述的方法,其中所述眼睛具有光轴,照射步骤a)还包括在与眼睛光轴基本垂直的多个不同平面上聚焦红外光。
10.根据权利要求9所述的方法,其中所述平面与所述角膜的前表面相交。
11.根据权利要求9所述的方法,还包括一个制作所述角膜的前表面的至少一部分的地形图的额外步骤。
12.根据权利要求9所述的方法,其中所述平面与所述角膜的后表面相交。
13.根据权利要求12所述的方法,还包括一个制作所述角膜的后表面的至少一部分的形状图的额外步骤。
14.根据权利要求9所述的方法,其中照射步骤a)包括照射所述内部区域以及与所述内部区域相交的平面。
15.根据权利要求14所述的方法,还包括一个制作所述角膜的内部区域的至少一部分的地形图的额外步骤。
16.根据权利要求1所述的方法,其中所述红外光的波长大约为780nm。
17.一种为患者制作人工晶状体的方法,包括根据权利要求1所述的方法测定患者角膜的形状并根据测得的角膜形状确定患者需要的屈光度校正的步骤。
18.根据权利要求17所述的方法,还包括其它的步骤:
a)选择尺寸适宜用作人工晶状体的透镜坯料;以及
b)使用激光器调整所述透镜坯料的点折射率以获得确定的屈光度校正。
19.根据权利要求17所述的方法,还包括一个根据确定的角膜形状确定患者需要的非球面校正的额外步骤。
20.根据权利要求19所述的方法,还包括其它的步骤:
a)选择尺寸适宜用作人工晶状体的透镜坯料;以及
b)使用激光器调整所述透镜坯料的点折射率以获得确定的屈光度和球面校正。
21.根据权利要求17或19所述的方法,包括一个根据确定的角膜形状确定患者需要的环面校正的步骤。
22.根据权利要求19所述的方法,还包括其它的步骤:
a)选择尺寸适宜用作的透镜坯料;以及
b)使用激光器调整透镜坯料的点折射率以获得确定的屈光度和环面校正。
23.根据权利要求19所述的方法,还包括其它的步骤:
a)选择尺寸示意用作人工晶状体的透镜坯料;以及
b)用激光器调整透镜坯料的点折射率以获得确定的屈光度、球面和和环面校正。
24.一种用于确定眼睛角膜形状的设备,所述角膜具有前表面、后表面和位于所述前表面和后表面之间的内部区域,该设备包括:
a)用于照射角膜的选定区域的激光器,所述选定区域包括所述前表面、后表面和内部区域中的至少一个,并使用具有能使被照射的角膜部分产生荧光的波长的红外光进行照射;
b)用于在角膜的选定区域中聚焦光线的聚焦装置;以及
c)产生的荧光的光检测器。
25.根据权利要求1所述的设备,其中所述选定的区域包括所述内部区域。
26.根据权利要求1所述的设备,其中所述眼睛具有光轴,所述聚焦装置在与眼睛光轴基本垂直的多个不同的平面上聚焦所述红外光。
27.根据权利要求1所述的设备,其中所述眼睛具有光轴,所述聚焦装置在与眼睛光轴基本垂直的多个不同的平面上聚焦红外光。
28.一种测定患者视力清晰度的方法,包括以下步骤:
a)用具有能使视网膜的色素上皮细胞中的蛋白质产生荧光的波长的扫描光线照射患者眼睛,所述扫描光线包括多个光束;
b)检测蛋白质荧光所产生的图像的清晰度;以及
c)调整所述扫描光线的至少一部分光束的路径长度,以增大所述荧光产生的图像的清晰度。
29.根据权利要求27所述的方法,其中所述扫描光线的波长为大约750至大约800nm。
30.根据权利要求28所述的方法,其中所述扫描光线的波长大约为780nm。
31.根据权利要求27所述的方法,其中所述患者具有人工晶状体。
32.根据权利要求27所述的方法,其中照射步骤a)包括照射视网膜的光检测器,以从中产生荧光。
33.根据权利要求27所述的方法,其中调整步骤c)包括用相位板补偿器调整所述路径长度。
34.根据权利要求27所述的方法,其中调整步骤c)包括用活动反射镜补偿器调整所述路径长度。
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