HK1180927B - System for characterizing a cornea and obtaining an ophthalmic lens - Google Patents

Description

System for characterizing a cornea and manufacturing an ophthalmic lens

Cross application

This application claims the benefit of the following U.S. provisional applications: 61/209,362 filed on 3/4/2009, 61/209,363 filed on 3/4/2009, 61/181,420 filed on 5/27/2009, 61/181,519 filed on 5/27/2009, and 61/181,525 filed on 5/27/2009. Each of these U.S. provisional applications is hereby incorporated by reference herein in its entirety. However, in the event that the following description is inconsistent with the disclosures of these provisional applications, the following description shall control.

Background

Various systems for characterizing the cornea are known and use the information of the characterization to produce ophthalmic lenses. See, for example, U.S. patent nos. 6413276, 6511180, 6626535 and 7241311.

A difficulty with known systems for characterizing the cornea is that the properties of the human cornea can be affected by the amount of moisture present at the time of measurement. Thus, for example, when an ophthalmic lens is made for a patient, if the cornea of the patient is characterized in a dry eye environment, then the lens will not fit the patient when the patient's eye contains a significant amount of moisture.

Another problem with conventional systems is that the internal structure of the cornea is generally not considered. We believe that the focusing effect of the cornea is achieved by the combination of the anterior surface of the cornea, the posterior surface of the cornea, and the internal structure of the cornea, which act by approximately 80%, 10%, and 10%, respectively. Failure to take into account the internal structure of the cornea, and in some cases the shape of the posterior surface of the cornea, will result in a lens that will not provide satisfactory vision.

Accordingly, there is a need to provide an improved system for characterizing the cornea in order to produce an ophthalmic lens that can be placed into the human eye. More desirably, the system can analyze the effectiveness of a placed lens to focus light on the retina.

The present invention also includes a system for determining the clarity of vision in a patient to determine the effectiveness of an implanted lens or other ophthalmic correction administered to the patient. According to the method, the patient's eye is illuminated with scanning light of a wavelength that produces fluorescence on the retina, and the sharpness of the image produced by the fluorescence is detected, for example, by a photodetector. Fluorescence is produced by proteins in the pigment epithelial cells of the retina and photoreceptors of the retina.

Subsequently, the path length of the scanning light line is adjusted to increase the sharpness of the image produced by the fluorescence. The scanning light is typically at a wavelength of 750 to about 800nm, preferably about 780 nm.

Disclosure of Invention

The present invention provides a system that meets the needs. The system includes a method and apparatus for determining the shape of a cornea of an eye, wherein the cornea has an anterior surface, a posterior surface, and an interior region between the anterior and posterior surfaces. The present method relies on fluorescence generated by the cornea, unlike the prior art which uses the reflectance of incident light to determine the shape of the cornea. According to the method, at least one of the anterior surface, the posterior surface, and the interior region of the cornea is illuminated with infrared light having a wavelength that fluoresces the illuminated portion of the cornea. The resulting fluorescence is detected. The detected fluorescence is used to map the shape of the anterior surface, posterior surface and/or interior regions of the cornea. "anterior surface" refers to the surface of the eye that faces outwardly. The "posterior surface" faces posteriorly toward the retina.

For example, in the case of the anterior region of the cornea, the optical path lengths are measured at a plurality of positions in the internal region. The presence of blue light produced by the inner region indicates the presence of a thin layer of collagen within the cornea.

Preferably, the step of illuminating comprises focusing the infrared light on a plurality of different planes substantially perpendicular to the optical axis of the eye. These planes may be interleaved with the anterior surface of the cornea, the posterior surface of the cornea, and/or the interior region of the cornea.

The invention also comprises a device for implementing the method. A preferred apparatus comprises a laser for irradiating a selected portion of the cornea with infrared light having a wavelength capable of fluorescing the irradiated portion of the cornea, focusing means and a detector; a focusing device, such as a focusing lens, for focusing light on a selected portion of the cornea; and a detector, such as a photodiode detector, that detects the generated fluorescence.

The present invention also includes a system for determining the clarity of vision in a patient to determine the utility of an implanted lens or other ophthalmic correction administered to the patient. According to this method, the patient's eye is irradiated with scanning light having a wavelength that causes fluorescence on the retina, and the sharpness of an image resulting from the fluorescence is detected, for example, with a photodetector. Fluorescence is produced by proteins in the pigment epithelium of the retina and photoreceptors of the retina. Subsequently, the path length of the scanning light line is adjusted to increase the sharpness of the image produced by the fluorescence. The incident light typically has a wavelength of 750 to about 800nm, preferably about 780 nm. The term "visual acuity" refers to the ability of a subject to distinguish between two images of different brightness (white at 100% brightness and black at 0% brightness). The smaller the contrast difference (relative brightness) between two different images that a subject can perceive, the higher the subject's visual acuity.

Drawings

These and other features, aspects, and advantages of the present invention will become better understood with regard to the following description, appended claims, and accompanying drawings where:

FIG. 1 is a schematic view of the method of the present invention for an intraocular lens eye;

FIG. 2 is a graphical representation of the spherical aberration present in the lens of an eye after a human eye and laser vision correction surgery;

FIG. 3 is a schematic illustration of one computational way to determine the sharpness of a retinal image;

FIG. 4 is a pictorial diagram of a mathematical procedure that can be used to determine the convolution in the calculation method of visual acuity;

FIG. 5 is a side cross-sectional view showing the stress-strain distribution in a loaded cornea as a result of Finite Element Modeling (FEM);

FIG. 6 is a schematic diagram showing the physical processes of second harmonic imaging (SHGi) and two-photon excited fluorescence imaging (TPEFi);

FIG. 7 schematically illustrates the major components of a two-photon microscope/ophthalmoscope useful in the present invention;

FIG. 8 is an overview of SHGi for collagen tissue structure;

FIG. 9 illustrates micro-morphometric features of the cornea;

FIG. 10 shows a schematic diagram of a synthetic corneal topography made over a field of view of a size similar to a custom intraocular lens (C-IPSM); and

fig. 11 is a schematic diagram of a system for detecting the sharpness of an image obtained by a lens implanted in an eye.

Detailed Description

SUMMARY

A system for determining corneal topography (including topography of the anterior and posterior surfaces and interior regions of the cornea) includes measurement and simulation steps that provide values of the refractive index profile within the cornea. Statistical distributions and results of finite element modeling of the corneal internal stress/strain relationship can be used.

The apparatus used in the present invention may be a two-photon microscope to obtain a plurality of measurements of high spatial resolution. Each individual beam employed by the apparatus has a unique optical path length. Methods of second harmonic imaging (SHGi) and two-photon excitation fluorescence imaging (TPEFi) can be employed. Using the plurality of pixel data generated by these measurements, a detailed spatial distribution of the refractive properties of the cornea can be evaluated, thus enabling the production of intraocular lenses that accurately compensate for the detected aberrations.

The system also includes methods for determining the effectiveness of the intraocular lens, such as quality control methods.

Characterization of the cornea

Referring initially to fig. 1, a system for determining the refractive characteristics of an implanted lens, such as a customized intraocular lens, is schematically illustrated and designated 10. The plurality of light beams 40 propagate through an intraocular lens implanted in a customized intraocular lens 20 that can provide high spatial resolution and locally correct the optical path length of each light beam. These rays are directed through the pseudophakic eye to form an image on retina 30. The plurality of individual beams 40 are characterized by each beam having a unique optical path length. More specifically, each optical path length represents the refraction that each beam experiences during its propagation through the eye. Next, the entire optical path length is collected with a computer, creating a digitized image on the retina of the eye. The plurality of light beams 40 propagate sequentially through the anterior surface 12 of the cornea 14, the interior region 13 of the cornea 14, the posterior surface 16 of the cornea 14, and the customized intraocular lens having the anterior surface layer 22, and form a focused image on the retina 30. The method of making the lens 20 is described in a co-pending application filed on even date under application number 12/717,886 entitled "System for making and adjusting lenses and lenses made therefrom" (docket 19780-1), which is hereby incorporated by reference as part of the present disclosure.

In the upper portion of the plurality of beams 40, three adjacent beams 42, 44, and 46 are shown, representing a local region in the zoning method. Generally speaking, in high spatial resolution ray tracing calculations, tens of millions of rays are evaluated based on their optical path lengths in the human eye. For computational purposes, a reference plane 18 is chosen that is close to the natural pupil of the pseudophakic eye, thereby normalizing the optical path length of the individual beams. More specifically, the propagation of a single ray from the pupil plane 18 to the anterior surface 22 of the customized intraocular lens 20 may be expressed as exp (ix (2 π/λ) xn (x, y) xz (x, y)), where exp is similar to an exponential function, i represents the number of imaginary units, π is equal to about 3.14, λ represents the wavelength of the ray, n (x, y) represents the local refractive index, and z (x, y) represents the actual distance of the lateral position from the pupil plane 18 with coordinates x and y. Any errors in positioning of the customized intraocular lens (C-IPSM) 20 with respect to axial or lateral position or tilt during lens implantation can be expressed in terms of the actual length z (x, y) values, and such errors can also be compensated for by in vivo fine tuning of the surface layer 22 using optical techniques such as described in applicant's co-pending application No. 12/717,886 filed on the same day as above, entitled "system for making and adjusting lenses and lenses made therefrom" (case 19780-1), which is hereby incorporated by reference as part of this document.

Figure 2 shows a particular optical aberration, such as spherical aberration, of a human eye present in a normal eye (e.g., the crystalline lens) and a post-laser in situ keratomileusis eye (e.g., a reshaped cornea), showing the induction of spherical aberration in the post-laser in situ keratomileusis eye 60. In the upper part of fig. 2, the situation of a normal eye 50 is shown by way of example. The eyeball 52 comprises a cornea 56, a lens 54, and a retina 58. Typically, for a pupil diameter of 6mm, a spherical aberration 59 of about one wavelength λ corresponding to 0.5 μm is introduced, which is mainly related to the spherical shape of the lens. In the lower part of fig. 2, the introduction of a large amount of spherical aberration is illustrated in the case of an eye 60 after undergoing a myopia correction surgery. Eyeball 62 has cornea 66, lens 64, and retina 68. Spherical aberration of about 10 wavelengths λ (10 λ) corresponding to 5 μm is typically encountered, which is mainly associated with the edge of the central flattened cornea.

Fig. 3 is a schematic diagram of a computational pathway 70 for determining the necessary refractive effect of an implanted lens. The various beams 72 are transformed into a pupil function 74, which can be thought of as the spatial distribution of path lengths 76, and can be expressed by the mathematical expression 78: p (x, y) = P (x, y) exp (ikW (x, y)), where P (x, y) is amplitude and exp (ikW (x, y)) is synthetic pupilThe phase of the aperture function. The phase depends on the wave vector k =2 π r/λ, λ being the wavelength of the individual beams, W (x, y) being its path length, i representing the number of imaginary units. A Point Spread Function (PSF)80 may be derived from the pupil function 74 and may be mathematically expressed as a Fourier transform 82, PSF (x, y) = | FT (P (x, y)), (phi)²It can also be represented graphically as a pseudo three-dimensional function 84, showing a near diffraction limited case, showing that the pseudophakic eye has only minor optical aberrations. The steckel ratio i 86 can be calculated from equation 70 according to 88: i = (max (PSF (x, y))/max (PSFdiff (x, y)) derivative, where PSF (x, y) represents the point spread function of an aberrated optical system, and PSFdiff (x, y) is similar to an idealized diffraction-limited optical system.

Fig. 4 is a pictorial representation of the mathematical process of convolution calculations that can be used to evaluate the sharpness of a retinal image. The imaging process 90 can be visualized as a mathematical operation process called convolution 94 in which an idealized image of the object 92 is blurred by wrapping each image point around the point spread function PSF96 of the optical system to obtain the image 100. In the case of a human eye with a pupil diameter of 6mm, the PSF96 is shown as a pseudo three-dimensional map 98. Thus, the sharpness of the retinal image 100 can be confirmed by the point spread function PSF 96.

Fig. 5 is a side cross-sectional view showing stress and strain distribution in a loaded cornea as a result of Finite Element Modeling (FEM). By simulating the distribution of stresses 104 and strains 106 on the loaded cornea using a Finite Element Modeling (FEM) algorithm 102, the local density of stromal tissue within the cornea can be determined, and from this density the spatial distribution n (x, y) of the refractive index can be derived, resulting in a measure of the variability of the optical path lengths of the various beams within the cornea. First, Finite Element Modeling (FEM) provides a distribution of stiffness parameters in volume elements that is proportional to local tissue density. The use of FEM modeling in corneal biomechanics is described, for example, in Biomechan. Model Mechanobiology 5237-246, 2006 to A.Pandolf ϊ et al. An intraocular pressure of 2 kilopascals (kPA) (15mmHg) was also applied to the posterior surface. Only the front elastic layer 108 is secured intact on the edges. On the left part of fig. 5, the cauchy stress distribution along the radial direction is shown; the absolute value ranges from-2.5 kPa to +2.5 kPa. On the right part of fig. 5, the maximum principal strain distribution is shown; the relative compression or expansion of stromal tissue is between-0.07 to + 0.07.

Characterization of the cornea by fluorescence emission

Fig. 6 is a schematic diagram showing the physical processes of second harmonic imaging (SHGi) and two-photon excitation fluorescence imaging (TPEFi). On the upper left side of fig. 6, the principle of second harmonic imaging (SHGi)140 is shown. Adding frequency omega consecutively_pGenerates a transient reradiation from the energy level 144 to 142 having a frequency 2 omega_pOf the photon 150. On the upper right side of fig. 6, the two-photon excitation fluorescence imaging (TPEFi) process is visualized. Frequency me hungry omega_pThe two photons 156 and 158 excite the molecule from the ground level 152 to the excited level 154. Since the molecule is de-excited to energy level 162 within about 1 nanosecond, the fluorescence photon ω is thermally radiated to energy level 160 within about 1 picosecond_FAnd radiating again. In the lower part of fig. 6, the wavelength dependence of the imaging process of SHGi (second harmonic generation) and TPEFi (two-photon excited fluorescence) is illustrated. Usually, since the frequency is ω_pIs irradiated with a femtosecond laser beam having a frequency of 2 omega reduced from 166 to 170 via 168_pOf SHGi signals 174, 176 and 178, and having a frequency ω_FThe strength of the TPEFi signals 182, 184 and 186 increases. In a two-photon corneal microscope/ophthalmoscope, as depicted in fig. 7, an illuminating femtosecond laser with a wavelength of 780nm was used to optimize contrast of imaging of collagen fibers and cell processes inside the cornea.

Figure 7 schematically illustrates a preferred apparatus 702 for characterizing a corneal design customized intraocular lens. The apparatus 702 comprises a laser 704, preferably a two-photon laser; a control unit 706 and a scanning unit 708. Two-photon excitation microscopy is a fluorescence imaging technique capable of imaging viable tissue to a depth of 1 mm. Two-photon excitation microscopes are a special model of multiphoton fluorescence microscopes. Two-photon excitation is preferred over confocal microscopy due to its deeper tissue penetration, efficient light detection and less radiation damage. The conceptual basis for two-photon excitation is a fluorophore that can be excited in one quantum level by a low-energy two-photon, resulting in a fluorescent photon being emitted, typically, at a higher energy than either of the two excited photons. The probability of near simultaneous absorption of two photons is very low. Therefore, a high flux of excitation photons is typically required, often a femtosecond laser.

Suitable lasers may be available from calimar laser, sonerville, ca. The laser emits each pulse having a duration of about 50 to about 100 femtoseconds and an energy level of at least about 0.2 nJ. Preferably, laser 704 produces about 5 million pulses per second with a wavelength of 780nm, a pulse length of about 50fs, a pulse energy per pulse of about 10nJ, and the laser is a 500mW laser. The emitted laser beam 720 is directed by a turning mirror 722 through a neutral filter 724 to select the pulse energy. The diameter of the laser beam 720 emitted by the laser is typically about 2 mm. The laser beam 720 then passes through the dichroic mirror 728 and then to the scanning unit 708, which scanning unit 708 spatially distributes the pulses into a plurality of forms of beams. The computer control system 730 controls the scanning unit 708 to scan the cornea 732 in the eye.

The diameter of the beam 720 emitted by the laser is approximately 2 to 2.5 mm. The beam 720 exiting the scanner 708 is then focused by a focusing device to a size suitable for scanning the cornea 732, typically a beam having a diameter of about 1 to 2 μm. The focusing means may be any series of lenses and optical devices, such as prisms, that can be used to reduce the laser beam to a desired size. The focusing device may be a pair of telescopic lenses 742 and 744 and a microscope objective 746, wherein a second turning mirror 748 directs the light beams from the lens pair to the microscope objective. The focusing microscope objective may be a 40x/0.8 objective with a working distance of 3.3 mm. The scanning and control unit is preferably a Heidelberg spectra HRA scanning unit from Heidelberg Engineering, Heidelberg, Germany.

The optics in the scanning unit have a region of about 150 to 450 μm in diameter that can be scanned without moving the cornea 732 or the optics. To scan other areas of the cornea, the cornea must be moved in the x, y plane. At the same time, in order to scan different depths of the cornea, the focal plane of the laser scanner must be moved in the z-direction.

The control unit 706 may be any computer including a memory, a processor, a display, and an input device such as a mouse and/or a keyboard. The control unit is programmed to cause the laser beam from the scanning unit 708 to have a desired pattern.

Cells on the anterior surface of the cornea 732 will fluoresce under excitation by a 780nm laser beam, producing green light at a wavelength of about 530 nm. The emitted light follows the path of the incident laser light, i.e., the incident light passes through the microscope objective 746, is reflected by the turning mirror 748 through lenses 744 and 742, passes through the scanning unit 708 into the dichroic mirror 728, which reflects the fluorescent light to the path 780, generally at right angles to the path of the incident light passing through the dichroic mirror 728. In path 780, the emitted light passes through a filter 782, which filters out light having unwanted frequencies, and then through a focusing lens 784 to a light detector 786. The light detector may be an avalanche photodiode. The data obtained by the light detector may be stored in a memory or other memory of the computer control unit 730.

Thus, the anterior surface of the cornea is irradiated with infrared light having a wavelength capable of generating fluorescence, and the generated fluorescence is detected. For the anterior surface, the incident infrared light is focused on a number of different planes substantially perpendicular to the eye's optical axis, where the planes intersect the anterior surface of the cornea.

The same procedure can be used to characterize the posterior surface, focusing infrared light on a number of different planes substantially perpendicular to the optical axis of the eye, where the planes intersect the anterior surface of the cornea. Scanning is performed on 64 separate planes with beams spaced approximately 3 microns apart.

Scanning the interior of the cornea differs in that the thin layer of collagen in the interior region produces blue light rather than green light. The wavelength of blue light is about 390 nm. When scanning the interior of the cornea, another filter 732 must be used to confirm that the blue light has passed through the filter to the photodetector 786.

Fig. 8 is an overview of SHG imaging of collagen tissue structures. The collagen triple helix 188 is visualized on the upper left side of fig. 8, showing the typical structure of collagen fibers. Collagen fibers are a synthetic three-dimensional layered structure of organisms located within the corneal stroma. In the lower left side of fig. 8, the process of Second Harmonic Generation (SHG) laser/collagen fiber interaction is shown. Photon 194 at frequency ω polarizes the farther away fiber to an intermediate energy level 196, however, a second photon 198 at the same frequency ω also produces a momentary electronic energy level 192. The electron excitation is immediately re-radiated as a photon 200 of double energy at a frequency of 2 omega. This process allows higher yields to be obtained due to the unidirectional shape of the collagen fibrils. Second harmonic imaging of corneal tissue (SHGi) has been recently reported (m.han, g.giese, and j.f.bille, "second harmonic imaging of collagen fibers in the cornea and sclera," opt. express13, 5791-. The measurements were performed with the apparatus of fig. 7. The SHGi signal is determined according to equation 224 from the nonlinear optical polarization 226 of the collagen fibers. Signal strength 228 and second order polarization term [ chi ]⁽²⁾⁾]²Directly proportional to the inverse proportion of the pulse length pi of the femtosecond laser pulse. Thus, as illustrated in fig. 7, the high contrast SHGi image visually shows the three-dimensional layered structure of the corneal stroma due to the strong unidirectionality of collagen fibers and the ultrashort pulse length of the femtosecond laser used in the two-photon corneal microscope/ophthalmoscope.

Anatomically, figure 9 shows the cornea 14 of an eye comprising, from its anterior surface 12 to its posterior surface 16, an epithelium 230, an anterior elastic layer 244, a stroma 246, a posterior elastic layer 248, and an endothelium 250. Epithelium 230 is composed of multiple cell layers, such as cell layers 232, 234, 236, 238, and 240 incorporated into a base cell layer 242. The two-photon excited autofluorescence mode (TPEF) of the two-photon corneal microscope clearly images the basal cell layer 242 as well as the anterior surface 12, allowing spatially resolved measurements of the thickness of the epithelium 230. The endothelium can also be imaged with the two-photon excited autofluorescence mode of a two-photon corneal microscope to obtain a spatially resolved measurement of the thickness of the cornea 14. The stroma 246 is composed of approximately 200 collagen lamellae, e.g., 252, 254, 256, 258, 260, 262, and 264, having a synthetic three-dimensional structure that can be evaluated using the second harmonic imaging (SHGi) mode of two-photon corneal microscopy. Based on these measurements, as exemplified in fig. 5, the three-dimensional distribution of refractive index inside the cornea can be reconstructed with the support of Finite Element Modeling (FEM) of collagen structural stiffness. Thus, the optical path lengths of the multiple beams inside the cornea in the ray tracing calculation can be determined with high spatial resolution. Thus, the anterior surface, posterior surface, and/or internal structure of the cornea may be topographically mapped.

In fig. 10, a composite corneal shape map 270 formed from a plurality of individual imaging regions is shown. Typically, the central imaging region 280 extends beyond a diameter of about 2mm, including approximately 2000x2000 imaging pixels, for a total of 4 million imaging points or pixels, resulting in a resolution of approximately 1 μm (e.g., using a Nikon 50x/0.45 microscope objective). The synthetic corneal shape map 270 comprises a three-dimensional stack of two-photon microscopy images, consisting of either two-photon excited fluorescence imaging (TPEFi) or second harmonic imaging (SHGi) -imaging models. To match the size of a custom intraocular lens with a diameter of approximately 6mm, 6 peripheral imaging regions 290, 292, 294, 296, 298, and 300 were employed. The positioning of the monomer regions is achieved using a run-time cross-correlation algorithm of gray-value pixels in the overlap regions 310, 312, 314, 316, 318 and 320. Thus, the synthetic corneal topography has approximately 2 thousand 8 million data, providing a spatially resolved synthetic image of one transverse slice through the cornea. Typically, the optical path length of multiple light beams as they pass through the cornea of an intraocular lens eye is reconstructed with one hundred transverse slices through the cornea.

Designing and fabricating lenses

Methods of designing lenses based on data obtained from the apparatus of fig. 7 are well known in the art and include those described in U.S. patent 5,050,981 to Roffman, which is hereby incorporated as part of the present invention. Methods of making or adjusting lenses are also described in applicant's aforementioned co-pending U.S. patent 12/717,886 (docket 19780-1).

Determination of visual acuity

Referring to fig. 11, which schematically illustrates a system for determining the clarity of a patient's vision, in the example of fig. 11, there is also an implanted intraocular lens 1102. The system for this is substantially the same as the apparatus shown in fig. 7, using the same laser 704 and scanner 708. Optionally, an adaptive optics module (AO module) 1104 may also be used for the purpose of simulating refractive correction effects related to image sharpness and depth of focus. The AO module 708 consists of a phase plate compensator and a movable mirror for the purpose of pre-compensating the single beam generated by the laser 704. An adaptive device for compensating for asymmetric aberrations in a light beam that can be used in the present invention is described in applicant's U.S. patent 7,611,244. A method and apparatus for pre-compensating the refractive characteristics of a person with adaptive optical feedback control is described in applicant's us patent 6,155,684. The use of a movable mirror is described in applicant's U.S. patent No. 6,220,707. The single beam 1112 passes through the cornea 1114, followed by the intraocular lens 1102, and is focused on the retina, forming a retinal image 1120. Since the wavelength of the incoming light is about 750 to about 800nm, preferably about 780nm, the fluorescent proteins and photoreceptors in the pigment epithelial cells will emit fluorescence at a frequency of about 530nm to about 550 nm. The emitted light is shown in fig. 11 by line 1122. The intensity of the emitted fluorescence indicates and finds a correspondence between the cornea 1114 and the intraocular lens 1102 focusing the incoming light beam, where a higher intensity shows a better focus. To determine whether improved focus is achieved, the path length of the incoming scanning light may be varied, such as by adjusting a phase plate or a movable mirror in the adaptive optics module 1104, in order to increase the sharpness of the image produced by the fluorescence.

Optionally, a visual stimulus 1124, such as a snellen chart, can be provided to obtain objective feedback to the patient regarding the clarity of vision.

Using this method, the effectiveness of implanted lenses, such as intraocular lenses (IOLs), corneal lenses or contact lenses, and in situ lens modifications (cornea, IOL and natural lens) can be determined.

Although the preferred embodiments have been described in detail, other embodiments are possible. For example, while the invention has been described with respect to the use of intraocular lenses, it will be appreciated that the data obtained to characterize the cornea may also be used to fabricate contact lenses and other lenses for implantation in the eye. Accordingly, the scope of the invention as claimed should not be limited by the description of the preferred embodiments contained herein.

Claims (10)

1. A method of creating a topography of a cornea (14, 56, 732) of an eye, said cornea (14, 56, 732) having an anterior surface (12), a posterior surface (16), and an interior region (13) located between said anterior surface (12) and said posterior surface (16), the method comprising the steps of:

a) illuminating a portion of the cornea (14, 56, 732) by scanning a plurality of different planes within the portion of the cornea (14, 56, 732) perpendicular to an optical axis of the eye using focused infrared light (40, 720), the plurality of planes intersecting:

i) a first portion of the front surface (12) and a first portion of the inner region (13),

ii) a second portion of the front surface (12), a second portion of the inner region (13) and a first portion of the rear surface (16), and

iii) a second portion of the rear surface (16) and a third portion of the inner region (13),

wherein the infrared light (40, 720) has a wavelength that produces fluorescence from the illuminated portion of the cornea (14, 56, 732) via nonlinear optical processing and a second harmonic generation imaging signal;

b) detecting fluorescence and detecting and evaluating second harmonic generation imaging signals generated from the illuminated portion of the cornea (14, 56, 732);

c) determining from the detected fluorescence a measure of the shape of the anterior (12) and posterior (16) surfaces and the spatially resolved thickness of the illuminated portion of the cornea (14, 56, 732);

d) determining a three-dimensional layered structure of corneal stromal tissue in the illuminated portion of the cornea (14, 56, 732) from the second harmonic generation imaging signals;

e) determining an optical path length (76) of the illuminated portion of the cornea (14, 56, 732) from the detected fluorescence and second harmonic generation imaging signals by deriving a spatial distribution of the reflectivity n (x, y) using finite element modeling;

f) a topographical map of the anterior surface (12), the posterior surface (16), and the interior region (13) is generated from the generated spatial distribution of optical path lengths (76) of the illuminated corneal (14, 56, 732) portions.

2. The method of claim 1 wherein the nonlinear optical process comprises a two-photon stimulated fluorescence imaging process and a detection step, the detection and evaluation step comprising detecting any generated green light, wherein the presence of the green light is indicative of the anterior surface (12) or the posterior surface (16) of the cornea (14, 56, 732).

3. The method of claim 1 wherein said nonlinear optical process comprises a two-photon stimulated fluorescence imaging process and a detection step, said detection and evaluation step comprising detecting any blue light produced, wherein the presence of blue light indicates the presence of a thin layer of collagen in the cornea (14, 56, 732).

4. The method of claim 3, wherein the blue light has a wavelength of 390 nanometers.

5. The method of claim 2, wherein the green light has a wavelength of 530 nanometers and the infrared light has a wavelength of 780 nanometers.

6. The method of claim 1, wherein step f) further comprises determining a three-dimensional distribution of refractive indices within the illuminated corneal section from a spatial distribution of optical path lengths within the illuminated corneal section.

7. The method as claimed in claim 1, wherein the wavelength range of the infrared light is 750-800 nm.

8. The method of claim 7, wherein the infrared light has a wavelength of 780 nm.

9. The method of claim 1, wherein the infrared is emitted as a pulse and has an energy level of at least 0.2 nJ.

10. An apparatus for creating a topography of a cornea (14, 56, 732) of an eye, said cornea (14, 56, 732) having an anterior surface (12), a posterior surface (16), and an interior region (13) located between said anterior surface (12) and said posterior surface (16), the apparatus comprising:

a) a laser (704) for illuminating a selected portion of the cornea (14, 56, 732) with infrared light (40, 720) having a wavelength that produces fluorescence and second harmonic generation imaging signals directly from the illuminated portion of the cornea (14, 56, 732) by nonlinear optical processing;

b) focusing means (742, 744) for focusing infrared light (40, 720) on a selected portion of the cornea (14, 56, 732);

c) a scanning and control unit (706) for scanning a plurality of different planes perpendicular to an optical axis of the eye within the selected portion of the cornea (14, 56, 732) using focused infrared light (40, 720), the plurality of planes intersecting:

1) a first portion of the front surface (12) and a first portion of the inner region (13),

2) a second portion of the front surface (12), a second portion of the inner region (13) and a first portion of the rear surface (16), and

3) a second portion of the rear surface (16) and a third portion of the inner region (13),

d) a photodetector (786) for detecting fluorescence and second harmonic generation imaging signals generated from the irradiated portion of the cornea (14, 56, 732); and

e) a computerized control unit that:

1) evaluating a second harmonic generated from the irradiated portion of the cornea (14, 56, 732) to generate an imaging signal;

2) determining from the detected autofluorescence measurements of the shape of the anterior (12) and posterior (16) surfaces and the spatially resolved thickness of the illuminated cornea (14, 56, 732);

3) determining a three-dimensional layered structure of corneal stromal tissue in the illuminated portion of the cornea (14, 56, 732) from the second harmonic generation imaging signals;

4) determining an optical path length (76) of the illuminated portion of the cornea (14, 56, 732) from the detected fluorescence by deriving a spatial distribution of the reflectance n (x, y) using finite element modeling;

5) a topographical map of the anterior surface (12), the posterior surface (16), and the interior region (13) is generated from the generated spatial distribution of optical path lengths (76) of the illuminated corneal (14, 56, 732) portions.