System and method for laser treatment of ocular tissue based on patient biometric data and apparatus and method for determining laser energy based on an anatomical model

A look-up table for use in determining an energy parameter for photodisrupting ocular tissue with a laser is generated by determining a plurality of individual spot size distributions, wherein each of the plurality of individual spot size distributions is based on a different set of simulated data and includes an expected spot size of a laser focus at each of a plurality of locations within a modeled target volume of ocular tissue. The plurality of individual spot size distributions are combined to obtain a final spot size distribution that includes a final expected spot size of the laser focus at the plurality of locations of the focus within the modeled target volume of ocular tissue. An energy value is assigned to the plurality of locations of the focus within the modeled target volume of ocular tissue based on the final expected spot size at that location.

TECHNICAL FIELD

The present disclosure relates generally to the field of medical devices and treatment of diseases in ophthalmology including glaucoma, and more particularly to systems, and methods for laser treatment based on patient biometric data, and apparatuses and methods for determining laser energy based on an anatomical model.

BACKGROUND

Before describing the different types of glaucoma and current diagnosis and treatments options, a brief overview of the anatomy of the eye is provided.

Anatomy of the Eye

With reference toFIGS.1-3, the outer tissue layer of the eye1includes a sclera2that provides the structure of the eye's shape. In front of the sclera2is a cornea3that is comprised of transparent layers of tissue that allow light to enter the interior of the eye. Inside the eye1is a crystalline lens4that is connected to the eye by fiber zonules5, which are connected to the ciliary body6. Between the crystalline lens4and the cornea3is an anterior chamber7that contains a flowing clear liquid called aqueous humor8. Encircling the perimeter of the crystalline lens4is an iris9which forms a pupil around the approximate center of the crystalline lens. As shown inFIG.2, a posterior chamber23is an annular volume behind the iris9and bounded by the ciliary body6, fiber zonules5, and the crystalline lens4. The vitreous humor10is located between the crystalline lens4and the retina11. Light entering the eye is optically focused through the cornea3and crystalline lens.

With reference toFIG.2, the corneoscleral junction of the eye is the portion of the anterior chamber7at the intersection of the iris9, the sclera2, and the cornea3. The anatomy of the eye1at the corneoscleral junction includes a trabecular meshwork12. The trabecular meshwork12is a fibrous network of tissue that encircles the iris9within the eye1. In simplified, general terms the tissues of the corneoscleral junction are arranged as follows: the iris9meets the ciliary body6, the ciliary body meets with the underside of the scleral spur14, the top of the scleral spur serves as an attachment point for the bottom of the trabecular meshwork12. The ciliary body is present mainly in the posterior chamber, but also extends into the very corner of the anterior chamber7. The network of tissue layers that make up the trabecular meshwork12are porous and thus present a pathway for the egress of aqueous humor8flowing from the anterior chamber7. This pathway may be referred to herein as an aqueous humor outflow pathway, an aqueous outflow pathway, or simply an outflow pathway.

Referring toFIG.3, the pathway formed by the pores in the trabecular meshwork12connect to a set of thin, porous tissue layers called the uveal15, the corneoscleral meshwork16, and the juxtacanalicular tissue17. The juxtacanalicular tissue17, in turn, abuts a structure called Schlemm's canal18. The Schlemm's canal18carries a mixture of aqueous humor8and blood from the surrounding tissue to drain into the venous system though a system of collector channels19. As shown inFIG.2, the vascular layer of the eye, referred to as the choroid20, is next to the sclera2. A space, called the suprachoroidal space21, may be present between the choroid20and the sclera2. The general region near the periphery of the wedge between the cornea3and the iris9, running circumferentially is called the irido-corneal angle13. The irido-corneal angle13may also be referred to as the corneal angle of the eye or simply the angle of the eye. The ocular tissues illustrated inFIG.3are all considered to be within the irido-corneal angle13.

With reference toFIG.4, two possible outflow pathways for the movement of aqueous humor8include a trabecular outflow pathway40and a uveoscleral outflow pathway42. With additional reference toFIG.2, aqueous humor8, which is produced by the ciliary body6, flows from the posterior chamber23through the pupil into the anterior chamber7, and then exits the eye through one or more of the two different outflow pathways40,42. Approximately 90% of the aqueous humor8leaves via the trabecular outflow pathway40by passing through the trabecular meshwork12, into the Schlemm's canal18and through one or more plexus of collector channels19before draining through a drain path41into the venous system. Any remaining aqueous humor8leaves primarily through the uveoscleral outflow pathway42. The uveoscleral outflow pathway42passes through the ciliary body6face and iris root into the suprachoroidal space21(shown inFIG.2). Aqueous humor8drains from the suprachoroidal space21, from which it can be drained through the sclera2.

The intra-ocular pressure of the eye depends on the aqueous humor8outflow through the trabecular outflow pathway40and the resistance to outflow of aqueous humor through the trabecular outflow pathway. The intra-ocular pressure of the eye is largely independent of the aqueous humor8outflow through the uveoscleral outflow pathway42. Resistance to the outflow of aqueous humor8through the trabecular outflow pathway40may lead to elevated intra-ocular pressure of the eye, which is a widely recognized risk factor for glaucoma. Resistance through the trabecular outflow pathway40may increase due to a collapsed or malfunctioning Schlemm's canal18and trabecular meshwork12.

Referring toFIG.5, as an optical system, the eye1is represented by an optical model described by idealized centered and rotationally symmetrical surfaces, entrance and exit pupils, and six cardinal points: object and image space focal points, first and second principal planes, and first and second nodal points. Angular directions relative to the human eye are often defined with respect to an optical axis24, a visual axis26, a pupillary axis28and a line of sight29of the eye. The optical axis24is the symmetry axis, the line connecting the vertices of the idealized surfaces of the eye. The visual axis26connects the foveal center22with the first and second nodal points to the object. The line of sight29connects the fovea through the exit and entrance pupils to the object. The pupillary axis28is normal to the anterior surface of the cornea3and is directed to the center of the entrance pupil. These axes of the eye differ from one another only by a few degrees and fall within a range of what is generally referred to as the direction of view.

Glaucoma

Glaucoma is a group of diseases that can harm the optic nerve and cause vision loss or blindness. It is the leading cause of irreversible blindness. Approximately 80 million people are estimated to have glaucoma worldwide and of these, approximately 6.7 million are bilaterally blind. More than 2.7 million Americans over age 40 have glaucoma. Symptoms start with loss of peripheral vision and can progress to blindness.

There are two forms of glaucoma, one is referred to as closed-angle glaucoma, the other as open-angled glaucoma. With reference toFIGS.1-4, in closed-angle glaucoma, the iris9in a collapsed anterior chamber7may obstruct and close off the flow of aqueous humor8. In open-angle glaucoma, which is the more common form of glaucoma, the permeability of ocular tissue may be affected by irregularities in the juxtacanalicular tissue17and inner wall of Schlemm's canal18a, and blockage of tissue in the irido-corneal angle13along the trabecular outflow pathway40.

As previously stated, elevated intra-ocular pressure (IOP) of the eye, which damages the optic nerve, is a widely recognized risk factor for glaucoma. However, not every person with increased eye pressure will develop glaucoma, and glaucoma can develop without increased eye pressure. Nonetheless, it is desirable to reduce elevated IOP of the eye to reduce the risk of glaucoma.

Methods of diagnosing conditions of the eye of a patient with glaucoma include visual acuity tests and visual field tests, dilated eye exams, tonometry, i.e. measuring the intra-ocular pressure of the eye, and pachymetry, i.e. measuring the thickness of the cornea. Deterioration of vision starts with the narrowing of the visual field and progresses to total blindness. Imaging methods include slit lamp examination, observation of the irido-corneal angle with a gonioscopic lens and optical coherence tomography (OCT) imaging of the anterior chamber and the retina.

Once diagnosed, some clinically proven treatments are available to control or lower the intra-ocular pressure of the eye to slow or stop the progress of glaucoma. The most common treatments include: 1) medications, such as eye drops or pills, 2) laser surgery, and 3) traditional surgery. Treatment usually begins with medication. However, the efficacy of medication is often hindered by patient non-compliance. When medication does not work for a patient, laser surgery is typically the next treatment to be tried. Traditional surgery is invasive, more high risk than medication and laser surgery, and has a limited time window of effectiveness. Traditional surgery is thus usually reserved as a last option for patients whose eye pressure cannot be controlled with medication or laser surgery.

Laser Surgery

With reference toFIG.2, laser surgery for glaucoma targets the trabecular meshwork12to decrease aqueous humor8flow resistance. Common laser treatments include Argon Laser Trabeculoplasty (ALT), Selective Laser Trabeculoplasty (SLT) and Excimer Laser Trabeculostomy (ELT).

ALT was the first laser trabeculoplasty procedure. During the procedure, an argon laser of 514 nm wavelength is applied to the trabecular meshwork12around 180 degrees of the circumference of the irido-corneal angle13. The argon laser induces a thermal interaction with the ocular tissue that produces openings in the trabecular meshwork12. ALT, however, causes scarring of the ocular tissue, followed by inflammatory responses and tissue healing that may ultimately close the opening through the trabecular meshwork12formed by the ALT treatment, thus reducing the efficacy of the treatment. Furthermore, because of this scarring, ALT therapy is typically not repeatable.

SLT is designed to lower the scarring effect by selectively targeting pigments in the trabecular meshwork12and reducing the amount of heat delivered to surrounding ocular tissue. During the procedure, a solid-state laser of 532 nm wavelength is applied to the trabecular meshwork12between 180 to 360 degrees around the circumference of the irido-corneal angle13to remove the pigmented cells lining the trabeculae which comprise the trabecular meshwork. The collagen ultrastructure of the trabecular meshwork is preserved during SLT.12. SLT treatment can be repeated, but subsequent treatments have lower effects on IOP reduction.

ELT uses a 308 nm wavelength ultraviolet (UV) excimer laser and non-thermal interaction with ocular tissue to treat the trabecular meshwork12and inner wall of Schlemm's canal18ain a manner that does not invoke a healing response. Therefore, the IOP lowering effect lasts longer. However, because the UV light of the laser cannot penetrate deep into the eye, the laser light is delivered to the trabecular meshwork12via an optical fiber inserted into the eye1through an opening and the fiber is brought into contact with the trabecular meshwork. The procedure is highly invasive and is generally practiced simultaneously with cataract procedures when the eye is already surgically open. Like ALT and SLT, ELT also lacks control over the amount of IOP reduction.

The use of femtosecond lasers for surgery of the trabecular meshwork in the treatment of glaucoma is new. Femtosecond laser pulses treat tissue by a process called photodisruption in which tissue at the focus of a beam is disrupted to elemental gas. The intent of treating the tissue in this manner is to create an aperture through which the intraocular pressure can be reduced. The “cutting efficiency” is a function of laser fluence, which is the ratio of energy per pulse to the area over which the energy is delivered, spot size. Once the laser fluence exceeds a breakdown threshold value, the tissue within a volume specified by the laser focus spot size is disrupted. If the laser fluence is less than the breakdown threshold, the focused laser does not affect the tissue. It is generally accepted that the breakdown threshold for ocular tissue is approximately 0.8 to 1.2 J/cm2.

Femtosecond lasers treat the trabecular meshwork by focusing a beam of femtosecond laser pulse from the cornea, through the anterior chamber, and into a spot on the iridocorneal angle. The size (diameter) of the spot changes depending upon the amount of optical aberrations introduced into the beam trajectory as it enters, and passes through, the eye to the trabecular meshwork. The location of the trabecular meshwork varies across the patient population due to anatomical differences in corneal anterior and posterior shape, corneal thickness, and corneal diameter. There is a unique beam trajectory for each patient and leading to a unique set of optical aberrations. Therefore, there is a spot size variation across the patient population—and for a fixed energy—a different fluence, resulting in varying cutting efficiency.

Due to this spot size variation and resulting variation in cutting efficiency, what is needed are systems, apparatuses, and method for laser surgery treatment of glaucoma that provide homogeneous cutting efficiency across the patient population.

SUMMARY

The present disclosure relates to a method of photodisrupting a target volume of ocular tissue with a laser. The target volume of ocular tissue is associated with an eye of a patient. The method includes placing a focus of a laser at an initial location within the target volume of ocular tissue; and applying photodisruptive energy by the laser at the initial location in accordance with an energy parameter that is based on the initial location of the focus within the target volume of ocular tissue.

The present disclosure also relates to a system for photodisrupting a target volume of ocular tissue with a laser. The target volume of ocular tissue is associated with an eye of a patient. The system includes a first optical subsystem, a second optical subsystem, and a control system coupled to the first optical subsystem and the second optical subsystem. The first optical subsystem includes one or more optical components configured to be coupled to the eye. The second optical subsystem includes a laser source configured to output a laser beam, and a plurality of components configured to one or more of focus, scan, and direct the laser beam through the one or more optical components, toward the target volume of ocular tissue. The control system is configured to control the focusing and the scanning of the laser beam to: place a focus of the laser beam at an initial location within the target volume of ocular tissue, and apply photodisruptive energy by the laser beam at the initial location in accordance with an energy parameter that is based on the initial location of the focus within the target volume of ocular tissue.

The present disclosure also relates to a method of generating a look-up table for use in determining an energy parameter for photodisrupting ocular tissue with a laser. The method includes determining a plurality of individual spot size distributions, wherein each of the plurality of individual spot size distributions is based on a different set of simulated data and includes an expected spot size of a focus of a laser beam at each of a plurality of locations within a modeled target volume of ocular tissue. The method also includes combining the plurality of individual spot size distributions to obtain a final spot size distribution that includes a final expected spot size of the focus at the plurality of locations of the focus within the modeled target volume of ocular tissue. The method further includes assigning an energy value to the plurality of locations of the focus within the modeled target volume of ocular tissue based on the final expected spot size at that location.

The present disclosure also relates to an apparatus for generating a look-up table for use in determining an energy parameter for photodisrupting ocular tissue with a laser. The apparatus includes a memory and a processing unit coupled to the memory. The processing unit is configured to determine a plurality of individual spot size distributions, wherein each of the plurality of individual spot size distributions is based on a different set of simulated data and includes an expected spot size of a focus of a laser beam at each of a plurality of locations within a modeled target volume of ocular tissue. The processing unit is further configured to combine the plurality of individual spot size distributions to obtain a final spot size distribution that includes a final expected spot size of the focus at the plurality of locations of the focus within the modeled target volume of ocular tissue. The processor is also configured to assign an energy value to the plurality of locations of the focus within the modeled target volume of ocular tissue based on the final expected spot size at that location.

It is understood that other aspects of apparatuses and methods will become apparent to those skilled in the art from the following detailed description, wherein various aspects of apparatuses and methods are shown and described by way of illustration. As will be realized, these aspects may be implemented in other and different forms and its several details are capable of modification in various other respects. Accordingly, the drawings and detailed description are to be regarded as illustrative in nature and not as restrictive.

DETAILED DESCRIPTION

Disclosed herein are systems, apparatuses, and methods for safely and effectively reducing intra-ocular pressure (IOP) in the eye to either treat or reduce the risk of glaucoma. The systems, apparatuses, and methods enable access to the irido-corneal angle of the eye and integrate laser surgery techniques with high resolution imaging to precisely diagnose, locate, and treat abnormal ocular tissue conditions within the irido-corneal angle that may be causing elevated IOP.

An integrated surgical system disclosed herein is configured to reduce intraocular pressure in an eye having a cornea, an anterior chamber, and an irido-corneal angle comprising an aqueous humor outflow pathway formed of a trabecular meshwork, a Schlemm's canal, and one or more collector channels branching from the Schlemm's canal. The integrated surgical system includes a first optical subsystem and a second optical subsystem. The first optical subsystem includes a window configured to be coupled to the cornea and an exit lens configured to be coupled to the window. The second optical subsystem includes an optical coherence tomography (OCT) imaging apparatus configured to output an OCT beam, a laser source configured to output a laser beam, and a plurality of components, e.g., lenses and mirrors, configured to condition, combine, or direct the OCT beam and the laser beam toward the first optical subsystem.

The integrated surgical system also includes a control system coupled to the OCT imaging apparatus, the laser source, and the second optical subsystem. The controller is configured to instruct the OCT imaging apparatus to output an OCT beam and the laser source to output a laser beam, for delivery through the cornea, and the anterior chamber into the irido-corneal angle. In one configuration, the control system controls the second optical subsystem, so the OCT beam and the laser beam are directed into the first optical subsystem along a second optical axis that is offset from the first optical axis and that extends into the irido-corneal angle along an angled beam path30.

Directing each of an OCT beam and a laser beam along the same second optical axis into the irido-corneal angle of the eye is beneficial in that it enables direct application of the result of the evaluation of the condition into the treatment plan and surgery with precision in one clinical setting. Furthermore, combining OCT imaging and laser treatment allows targeting the ocular tissue with precision not available with any existing surgical systems and methods. Surgical precision afforded by the integrated surgical system allows for the affecting of only the targeted tissue of microscopic size and leaves the surrounding tissue intact. The microscopic size scale of the affected ocular tissue to be treated in the irido-corneal angle of the eye ranges from a few micrometers to a few hundred micrometers. For example, with reference toFIGS.2and3, the cross-sectional size of the normal Schlemm's canal18is an oval shape of a few tens of micrometers by a few hundred micrometers. The diameter of collector channels19and veins is a few tens of micrometers. The thickness of the juxtacanalicular tissue17is a few micrometers, the thickness of the trabecular meshwork12is around a hundred micrometers.

The control system of the integrated surgical system is further configured to instruct the laser source to modify a volume of ocular tissue within the outflow pathway to reduce a pathway resistance present in one or more of the trabecular meshwork, the Schlemm's canal, and the one or more collector channels by applying the laser beam to ocular tissue defining the volume to thereby cause photo-disruptive interaction with the ocular tissue to reduce the pathway resistance or create a new outflow pathway.

The laser source may be a femtosecond laser or a picosecond laser. Such lasers provide non-thermal photo-disruption interaction with ocular tissue to avoid thermal damage to surrounding tissue. Further, unlike other surgical methods, with femtosecond laser treatment opening surface incisions penetrating the eye can be avoided, enabling a non-invasive treatment. Instead of performing the treatment in a sterile surgical room, the non-invasive treatment can be performed in a non-sterile outpatient facility.

The integrated surgical system may also include an optical coherence tomography (OCT) imaging apparatus for imaging the target volume of ocular tissue. An additional imaging component may be included to provide direct visual observation of the irido-corneal angle along an angle of visual observation. For example, a microscope or imaging camera may be included to assist the surgeon in the process of docking the eye to the patient interface or an immobilizing device, locating ocular tissues in the eye and observing the progress of the surgery. The angle of visual observation can also be along the angled beam path30to the irido-corneal angle13through the cornea3and the anterior chamber7.

Images from the OCT imaging apparatus and the additional imaging component providing visual observation, e.g. microscope, are combined on a display device such as a computer monitor. Different images can be registered and overlaid on a single window, enhanced, processed, differentiated by false color for easier understanding. Certain features are computationally recognized by a computer processor, image recognition and segmentation algorithm can be enhanced, highlighted, marked for display. The geometry of the treatment plan can also be combined and registered with imaging information on the display device and marked up with geometrical, numerical and textual information. The same display can also be used for user input of numerical, textual and geometrical nature for selecting, highlighting and marking features, inputting location information for surgical targeting by keyboard, mouse, cursor, touchscreen, audio or other user interface devices.

OCT Imaging

The main imaging component of the integrated surgical system disclosed herein is an OCT imaging apparatus. OCT technology may be used to diagnose, locate and guide laser surgery directed to the irido-corneal angle of the eye. For example, with reference toFIGS.1-3, OCT imaging may be used to determine the structural and geometrical conditions of the anterior chamber7, to assess possible obstruction of the trabecular outflow pathway40and to determine the accessibility of the ocular tissue for treatment. As previously described, the iris9in a collapsed anterior chamber7may obstruct and close off the flow of aqueous humor8, resulting in closed-angle glaucoma. In open-angle glaucoma, where the macroscopic geometry of the angle is normal, the permeability of ocular tissue may be affected, by blockage of tissue along the trabecular outflow pathway40or by the collapse of the Schlemm's canal18or collector channels19.

OCT imaging can provide the necessary spatial resolution, tissue penetration and contrast to resolve microscopic details of ocular tissue. When scanned, OCT imaging can provide two-dimensional (2D) cross-sectional images of the ocular tissue. As another aspect of the integrated surgical system, 2D cross-sectional images may be processed and analyzed to determine the size, shape and location of structures in the eye for surgical targeting. It is also possible to reconstruct three-dimensional (3D) images from a multitude of 2D cross-sectional images but often it is not necessary. Acquiring, analyzing and displaying 2D images is faster and can still provide all information necessary for precise surgical targeting.

OCT is an imaging modality capable of providing high resolution images of materials and tissue. Imaging is based on reconstructing spatial information of the sample from spectral information of scattered light from within the sample. Spectral information is extracted by using an interferometric method to compare the spectrum of light entering the sample with the spectrum of light scattered from the sample. Spectral information along the direction that light is propagating within the sample is then converted to spatial information along the same axis via the Fourier transform. Information lateral to the OCT beam propagation is usually collected by scanning the beam laterally and repeated axial probing during the scan. 2D and 3D images of the samples can be acquired this way. Image acquisition is faster when the interferometer is not mechanically scanned in a time domain OCT, but interference from a broad spectrum of light is recorded simultaneously. This implementation is called a spectral domain OCT. Faster image acquisition may also be obtained by scanning the wavelength of light rapidly from a wavelength scanning laser in an arrangement called a swept-source OCT.

The axial spatial resolution limit of the OCT is inversely proportional to the bandwidth of the probing light used. Both spectral domain and swept source OCTs are capable of axial spatial resolution below 5 micrometers (m) with sufficiently broad bandwidth of 100 nanometers (nm) or more. In the spectral domain OCT, the spectral interference pattern is recorded simultaneously on a multichannel detector, such as a charge coupled device (CCD) or complementary metal oxide semiconductor (CMOS) camera, while in the swept source OCT the interference pattern is recorded in sequential time steps with a fast optical detector and electronic digitizer. There is some acquisition speed advantage of the swept source OCT but both types of systems are evolving and improving rapidly, and resolution and speed is sufficient for purposes of the integrated surgical system disclosed herein. Stand-alone OCT systems and OEM components are now commercially available from multiple vendors, such as Optovue Inc., Fremont, CA, Topcon Medical Systems, Oakland, NJ, Carl Zeiss Meditec AG, Germany, Nidek, Aichi, Japan, Thorlabs, Newton, NJ, Santec, Aichi, Japan, Axsun, Billercia, MA, and other vendors.

Femtosecond Laser Source

The preferred surgical component of the integrated surgical system disclosed herein is a femtosecond laser. A femtosecond laser provides highly localized, non-thermal photo-disruptive laser-tissue interaction with minimal collateral damage to surrounding ocular tissue. Photo-disruptive interaction of the laser is utilized in optically transparent tissue. The principal mechanism of laser energy deposition into the ocular tissue is not by absorption but by a highly nonlinear multiphoton process. This process is effective only at the focus of the pulsed laser where the peak intensity is high. Regions where the beam is traversed but not at the focus are not affected by the laser. Therefore, the interaction region with the ocular tissue is highly localized both transversally and axially along the laser beam. The process can also be used in weakly absorbing or weakly scattering tissue. While femtosecond lasers with photo-disruptive interactions have been successfully used in ophthalmic surgical systems and commercialized in other ophthalmic laser procedures, none have been used in an integrated surgical system that accesses the irido-corneal angle.

In known refractive procedures, femtosecond lasers are used to create corneal flaps, pockets, tunnels, arcuate incisions, lenticule shaped incisions, partial or fully penetrating corneal incisions for keratoplasty. For cataract procedures the laser creates a circular cut on the capsular bag of the eye for capsulotomy and incisions of various patterns in the lens for breaking up the interior of the crystalline lens to smaller fragments to facilitate extraction. Entry incisions through the cornea opens the eye for access with manual surgical devices and for insertions of phacoemulsification devices and intra-ocular lens insertion devices. Several companies have commercialized such surgical systems, among them the IntraLase system now available from Johnson & Johnson Vision, Santa Ana, CA, The LenSx and WaveLight systems from Alcon, Fort Worth, TX the Lensar Laser System from Lensar, Inc. Orlando, FL; the family of Femto Lasers from Ziemer Ophthalmics, Alton IL; the Victus Femtosecond Laser Platform from Bausch and Lomb, Rochester, NY; and the Catalys Precision Laser System from Johnson & Johnson, Santa Ana, CA.

These existing systems are developed for their specific applications, for surgery in the cornea, and the crystalline lens and its capsular bag and are not capable of performing surgery in the irido-corneal angle13for several reasons. First, the irido-corneal angle13is not accessible with these surgical laser systems because the irido-corneal angle is too far out in the periphery and is outside of surgical range of these systems. Second, the angle of the laser beam from these systems, which is along the optical axis24to the eye1, is not appropriate for reaching the irido-corneal angle13, where there is significant scattering and optical distortion at the applied wavelength. Third, any imaging capabilities these systems may have do not have the accessibility, penetration depth and resolution to image the tissue along the trabecular outflow pathway40with sufficient detail and contrast.

In accordance with the integrated surgical system disclosed herein, clear access to the irido-corneal angle13is provided along the angled beam path30. The tissue, e.g., cornea3and the aqueous humor8in the anterior chamber7, along this angled beam path30is transparent for wavelengths from approximately 400 nm to 2500 nm and femtosecond lasers operating in this region can be used. Such mode locked lasers work at their fundamental wavelength with Titanium, Neodymium or Ytterbium active material. Non-linear frequency conversion techniques known in the art, frequency doubling, tripling, sum and difference frequency mixing techniques, optical parametric conversion can convert the fundamental wavelength of these lasers to practically any wavelength in the above mentioned transparent wavelength range of the cornea.

Existing ophthalmic surgical systems apply lasers with pulse durations longer than 1 ns have higher photo-disruption threshold energy, require higher pulse energy and the dimension of the photo-disruptive interaction region is larger, resulting in loss of precision of the surgical treatment. When treating the irido-corneal angle13, however, higher surgical precision is required. To this end, the integrated surgical system may be configured to apply lasers with pulse durations from 10 femtosecond (fs) to 1 nanosecond (ns) for generating photo-disruptive interaction of the laser beam with ocular tissue in the irido-corneal angle13. While lasers with pulse durations shorter than 10 fs are available, such laser sources are more complex and more expensive. Lasers with the described desirable characteristics, e.g., pulse durations from 10 femtosecond (fs) to 1 nanosecond (ns), are commercially available from multiple vendors, such as Newport, Irvine, CA, Coherent, Santa Clara, CA, Amplitude Systems, Pessac, France, NKT Photonics, Birkerod, Denmark, and other vendors.

Accessing the Irido-Corneal Angle

An important feature afforded by the integrated surgical system is access to the targeted ocular tissue in the irido-corneal angle13. With reference toFIG.6, the irido-corneal angle13of the eye may be accessed via the integrated surgical system along an angled beam path30passing through the cornea3and through the aqueous humor8in the anterior chamber7. For example, one or more of an imaging beam, e.g., an OCT beam and/or a visual observation beam, and a laser beam may access the irido-corneal angle13of the eye along the angled beam path30.

An optical system disclosed herein is configured to direct a light beam to an irido-corneal angle13of an eye along an angled beam path30. The optical system includes a first optical subsystem and a second optical subsystem. The first optical subsystem includes a window formed of a material with a refractive index nwand has opposed concave and convex surfaces. The first optical subsystem also includes an exit lens formed of a material having a refractive index nx. The exit lens also has opposed concave and convex surfaces. The concave surface of the exit lens is configured to couple to the convex surface of the window to define a first optical axis extending through the window and the exit lens. The concave surface of the window is configured to detachably couple to a cornea of the eye with a refractive index ncsuch that, when coupled to the eye, the first optical axis is generally aligned with the direction of view of the eye.

The second optical subsystem is configured to output a light beam, e.g., an OCT beam or a laser beam. The optical system is configured so that the light beam is directed to be incident at the convex surface of the exit lens along a second optical axis at an angle α that is offset from the first optical axis. The respective geometries and respective refractive indices nx, and nwof the exit lens and window are configured to compensate for refraction and distortion of the light beam by bending the light beam so that it is directed through the cornea3of the eye toward the irido-corneal angle13. More specifically, the first optical system bends the light beam to that the light beam exits the first optical subsystem and enters the cornea3at an appropriate angle so that the light beam progresses through the cornea and the aqueous humor8in a direction along the angled beam path30toward the irido-corneal angle13.

Accessing the irido-corneal angle13along the angled beam path30provides several advantages. An advantage of this angled beam path30to the irido-corneal angle13is that the OCT beam and laser beam passes through mostly clear tissue, e.g., the cornea3and the aqueous humor8in the anterior chamber7. Thus, scattering of these beams by tissue is not significant. With respect to OCT imaging, this enables the use of shorter wavelength, less than approximately 1 micrometer, for the OCT to achieve higher spatial resolution. An additional advantage of the angled beam path30to the irido-corneal angle13through the cornea3and the anterior chamber7is the avoidance of direct laser beam or OCT beam light illuminating the retina11. As a result, higher average power laser light and OCT light can be used for imaging and surgery, resulting in faster procedures and less tissue movement during the procedure.

Another important feature provided by the integrated surgical system is access to the targeted ocular tissue in the irido-corneal angle13in a way that reduces beam discontinuity. To this end, the window and exit lens components of the first optical subsystem are configured to reduce the discontinuity of the optical refractive index between the cornea3and the neighboring material and facilitate entering light through the cornea at a steep angle.

Having thus generally described the integrated surgical system and some of its features and advantages, a more detailed description of the system and its component parts follows.

Integrated Surgical System

In the following description, the term “beam” may—depending on the context—refer to one of a laser beam, an OCT beam, an illumination beam, an observation beam, an illumination/observation beam, or a visual beam. The term “colinear beams” refers to two or more different beams that are combined by optics of the integrated surgical system1000to share a same path to a same target location of the eye as they enter the eye. The term “non-colinear beams” refers to two or more different beams that have different paths into the eye. The term “co-targeted beams” refers to two or more different beams that have different paths into the eye but that target a same location of the eye. In colinear beams, the different beams may be combined to share a same path into the eye by dichroic or polarization beam splitters, and delivered along a same optical path through a multiplexed delivery of the different beams. In non-colinear beams, the different beams are delivered into the eye along different optical paths that are separated spatially or by an angle between them. In the description to follow, any of the foregoing beams or combined beams may be generically referred to as a light beam. The terms distal and proximal may be used to designate the direction of travel of a beam, or the physical location of components relative to each other within the integrated surgical system. The distal direction refers to a direction toward the eye; thus an OCT beam output by the OCT imaging apparatus moves in the distal direction toward the eye. The proximal direction refers to a direction away from the eye; thus an OCT return beam from the eye moves in the proximal direction toward the OCT imaging apparatus.

With reference toFIG.7, an integrated surgical system1000for non-invasive glaucoma surgery includes a control system100, a surgical component200, a first imaging component300and an optional second imaging component400. In the embodiment ofFIG.7, the surgical component200is a femtosecond laser source, the first imaging component300is an OCT imaging apparatus, and the optional second imaging component400is a visual observation apparatus, e.g., a microscope, for direct viewing or viewing with a camera. Other components of the integrated surgical system1000include beam conditioners and scanners500, beam combiners600, a focusing objective head700, and a patient interface800.

The control system100may be a single computer or and plurality of interconnected computers configured to control the hardware and software components of the other components of the integrated surgical system1000. A user interface110of the control system100accepts instructions from a user and displays information for observation by the user. Input information and commands from the user include but are not limited to system commands, motion controls for docking the patient's eye to the system, selection of pre-programmed or live generated surgical plans, navigating through menu choices, setting of surgical parameters, responses to system messages, determining and acceptance of surgical plans and commands to execute the surgical plan. Outputs from the system towards the user includes but are not limited to display of system parameters and messages, display of images of the eye, graphical, numerical and textual display of the surgical plan and the progress of the surgery.

The control system100is connected to the other components200,300,400,500of the integrated surgical system1000. Control signals from the control system100to the femtosecond laser source200function to control internal and external operation parameters of the laser source, including for example, power, repetition rate and beam shutter. Control signals from the control system100to the OCT imaging apparatus300function to control OCT beam scanning parameters, and the acquiring, analyzing and displaying of OCT images.

Laser beams201from the femtosecond laser source200and OCT beams301from the OCT imaging apparatus300are directed towards a unit of beam conditioners and scanners500. Beam conditioners set the basic beam parameters, beam size, divergence. Beam conditioners may also include additional functions, setting the beam power or pulse energy and shutter the beam to turn it on or off. Different kind of scanners can be used for the purpose of scanning the laser beam201and the OCT beam301. For scanning transversal to a beam201,301, angular scanning galvanometer scanners are available for example from Cambridge Technology, Bedford, MA, Scanlab, Munich, Germany.

To optimize scanning speed, the scanner mirrors are typically sized to the smallest size, which still support the required scanning angles and numerical apertures of the beams at the target locations. The ideal beam size at the scanners is typically different from the beam size of the laser beam201or the OCT beam301, and different from what is needed at the entrance of a focusing objective head700. Therefore, beam conditioners are applied before, after or in between individual scanners. The beam conditioner and scanners500includes scanners for scanning the beam transversally and axially. Axial scanning changes the depth of the focus at the target region. Axial scanning can be performed by moving a lens axially in the beam path with a servo or stepper motor.

Beam combiners, such as dichroic, polarization or other kind of beam combiners, colinearly combine the laser beam201and the OCT beam301. In some embodiments, the laser beam201and the OCT beam301may be combined and then scanned using a common scanner. In other embodiments, the laser beam201and the OCT beam301beams may be scanned using separate scanners and then colinearly combined. In either case, a combined laser/OCT beam550is colinearly combined with an illumination beam401of the visual observation apparatus400with dichroic, polarization or other kind of beam combiners600. The beam combiner600uses dichroic or polarization beam splitters to split and recombine light with different wavelength and/or polarization. The beam combiner600may also include optics to change certain parameters of the individual beams201,301,401such as beam size, beam angle and divergence. The combined laser/OCT/visual beam701is passed through optics of the focusing objective head700and optics of the patient interface800to reach a common target volume or surgical volume in the eye1.

To resolve ocular tissue structures of the eye in sufficient detail, the imaging components300,400of the integrated surgical system1000may provide an OCT beam and a visual observation beam having a spatial resolution of several micrometers. The resolution of the OCT beam is the spatial dimension of the smallest feature that can be recognized in the OCT image. It is determined mostly by the wavelength and the spectral bandwidth of the OCT source, the quality of the optics delivering the OCT beam to the target location in the eye, the numerical aperture of the OCT beam and the spatial resolution of the OCT imaging apparatus at the target location. In one embodiment, the OCT beam of the integrated surgical system has a resolution of no more than 5 μm.

Likewise, the surgical laser beam provided by the femtosecond laser source200may be delivered to targeted locations with several micrometer accuracy. The resolution of the laser beam is the spatial dimension of the smallest feature at the target location that can be modified by the laser beam without significantly affecting surrounding ocular tissue. It is determined mostly by the wavelength of the laser beam, the quality of the optics delivering the laser beam to target location in the eye, the numerical aperture of the laser beam, the energy of the laser pulses in the laser beam and the spatial resolution of the laser scanning system at the target location. In addition, to minimize the threshold energy of the laser for photo-disruptive interaction, the size of the laser spot should be no more than approximately 5 μm.

It should be noted that, while the observation beam401is acquired by the visual observation apparatus400using fixed, non-scanning optics, the OCT beam301of the OCT imaging apparatus300is scanned laterally in two transversal directions. The laser beam201of the femtosecond laser source200is scanned in two lateral dimensions and the depth of the focus is scanned axially.

For practical embodiments, beam conditioning, scanning and combining the optical paths are certain functions performed on the laser, OCT and visual observation optical beams. Implementation of those functions may happen in a different order than what is indicated inFIG.7. Specific optical hardware that manipulates the beams to implement those functions can have multiple arrangements with regards to how the optical hardware is arranged. They can be arranged in a way that they manipulate individual optical beams separately, in another embodiment one component may combine functions and manipulates different beams. For example, a single set of scanners can scan both the laser beam201and the OCT beam301. In this case, separate beam conditioners set the beam parameters for the laser beam201and the OCT beam301, then a beam combiner combines the two beams for a single set of scanners to scan the beams. While many combinations of optical hardware arrangements are possible for the integrated surgical system, the following section describes in detail an example arrangement.

Referring toFIG.8, an example integrated surgical system1000includes optical subsystems configured together to deliver each of a laser beam201, an OCT beam301, and an illumination beam401in the distal direction toward an eye1, and receive each of an OCT return beam and an observation beam401back from the eye1.

Regarding the delivery of a laser beam, a laser beam201output by the femtosecond laser source200passes through a beam conditioner510where the basic beam parameters, beam size, divergence are set. The beam conditioner510may also include additional functions, setting the beam power or pulse energy and shutter the beam to turn it on or off. After existing the beam conditioner510, the laser beam210enters an axial scanning lens520. The axial scanning lens520, which may include a single lens or a group of lenses, is movable in the axial direction522by a servo motor, stepper motor or other control mechanism. Movement of the axial scanning lens520in the axial direction522changes the axial distance of the focus of the laser beam210at a focal point.

In accordance with a particular embodiment of the integrated surgical system, an intermediate focal point722is set to fall within, and is scannable in, the conjugate surgical volume721, which is an image conjugate of the surgical volume720, determined by optics of the focusing objective head700. The surgical volume720is the spatial extent of the region of interest within the eye where imaging and surgery is performed. For glaucoma surgery, the surgical volume720is the vicinity of the irido-corneal angle13of the eye.

A pair of transverse scanning mirrors530,532rotated by a galvanometer scanner scan the laser beam201in two essentially orthogonal transversal directions, e.g., in the x and y directions. Then the laser beam201is directed towards a dichroic or polarization beam splitter540where it is reflected toward a beam combining mirror601configured to combine the laser beam201with an OCT beam301.

Regarding delivery of an OCT beam, an OCT beam301output by the OCT imaging apparatus300passes through a beam conditioner511, an axially moveable focusing lens521and a transversal scanner with scanning mirrors531and533. The focusing lens521is used set the focal position of the OCT beam in the conjugate surgical volume721and the real surgical volume720. The focusing lens521is not scanned for obtaining an OCT axial scan. Axial spatial information of the OCT image is obtained by Fourier transforming the spectrum of the interferometrically recombined OCT return beam301and reference beams302. However, the focusing lens521can be used to re-adjust the focus when the surgical volume720is divided into several axial segments. This way the optimal imaging spatial resolution of the OCT image can be extended beyond the Rayleigh range of the OCT signal beam, at the expense of time spent on scanning at multiple ranges.

Proceeding in the distal direction toward the eye1, after the scanning mirrors531and533, the OCT beam301is combined with the laser beam201by the beam combiner mirror601. The OCT beam301and laser beam201components of the combined laser/OCT beam550are multiplexed and travel in the same direction to be focused at an intermediate focal point722within the conjugate surgical volume721. After having been focused in the conjugate surgical volume721, the combined laser/OCT beam550propagates to a second beam combining mirror602where it is combined with a visual observation beam401to form a combined laser/OCT/visual beam701.

The combined laser/OCT/visual beam701traveling in the distal direction then passes through a relay lens750included in the focusing objective head700, is reflected by a reflecting surface740, which may be a planar beam-folding mirror or a facet inside an optic, and then passes through an exit lens710of the focusing objective head and a window801of a patient interface, where the intermediate focal point722of the laser beam within the conjugate surgical volume721is re-imaged into a focal point in the surgical volume720. The optics of the focusing objective head700re-images the intermediate focal point722, through the window801of a patient interface, into the ocular tissue within the surgical volume720. In one configuration, the reflecting surface740in the form of a facet inside an optic may have a specialized coating for broadband reflection (visible, OCT and femtosecond) and low difference between s and p polarization group delay dispersion (GDD).

A scattered OCT return beam301from the ocular tissue travels in the proximal direction to return to the OCT imaging apparatus300along the same paths just described, in reverse order. The reference beam302of the OCT imaging apparatus300, passes through a reference delay optical path and return to the OCT imaging apparatus from a moveable mirror330. The reference beam302is combined interferometrically with the OCT return beam301on its return within the OCT imaging apparatus300. The amount of delay in the reference delay optical path is adjustable by moving the moveable mirror330to equalize the optical paths of the OCT return beam301and the reference beam302. For best axial OCT resolution, the OCT return beam301and the reference beam302are also dispersion compensated to equalize the group velocity dispersion within the two arms of the OCT interferometer.

When the combined laser/OCT/visual beam701is delivered through the cornea3and the anterior chamber7, the combined beam passes through posterior and anterior surface of the cornea at a steep angle, far from normal incidence. These surfaces in the path of the combined laser/OCT/visual beam701create excessive astigmatism and coma aberrations that need to be compensated for.

With reference toFIGS.9aand9b, in an embodiment of the integrated surgical system1000, optical components of the focusing objective head700and patient interface800are configured to minimize spatial and chromatic aberrations and spatial and chromatic distortions.FIG.9ashows a configuration when both the eye1, the patient interface800and the focusing objective head700all coupled together.FIG.9bshows a configuration when both the eye1, the patient interface800and the focusing objective head700all detached from one another.

The patient interface800optically and physically couples the eye1to the focusing objective head700, which in turn optically couples with other optic components of the integrated surgical system1000. The patient interface800serves multiple functions. It immobilizes the eye relative to components of the integrated surgical system; creates a sterile barrier between the components and the patient; and provides optical access between the eye and the instrument. The patient interface800is a sterile, single use disposable device and it is coupled detachably to the eye1and to the focusing objective head700of the integrated surgical system1000.

The patient interface800includes a window801having an eye-facing, concave surface812and an objective-facing, convex surface813opposite the concave surface. The window801thus has a meniscus form. With reference toFIG.9c, the concave surface812is characterized by a radius of curvature re, while the convex surface813is characterized by a radius of curvature rw. The concave surface812is configured to couple to the eye, either through a direct contact or through index matching material, liquid or gel, placed in between the concave surface812and the eye1. The window801may be formed of glass and has a refractive index nw. In one embodiment, the window801is formed of fused silica and has a refractive index nwof 1.45. Fused silica has the lowest index from common inexpensive glasses. Fluoropolymers such as the Teflon AF are another class of low index materials that have refractive indices lower than fused silica, but their optical quality is inferior to glasses and they are relatively expensive for high volume production. In another embodiment the window801is formed of the common glass BK7 and has a refractive index nwof 1.50. A radiation resistant version of this glass, BK7G18 from Schott AG, Mainz, Germany, allows gamma sterilization of the patient interface800without the gamma radiation altering the optical properties of the window801.

Returning toFIGS.9aand9b, the window801is surrounded by a wall803of the patient interface800and an immobilization device, such as a suction ring804. When the suction ring804is in contact with the eye1, an annular cavity805is formed between the suction ring and the eye. When vacuum applied to the suction ring804and the cavity via a vacuum tube a vacuum pump (not shown inFIGS.9aand9b), vacuum forces between the eye and the suction ring attach the eye to the patient interface800during surgery. Removing the vacuum releases or detach the eye1.

The end of the patient interface800opposite the eye1includes an attachment interface806configured to attach to the housing702of the focusing objective head700to thereby affix the position of the eye relative to the other components of the integrated surgical system1000. The attachment interface806can work with mechanical, vacuum, magnetic or other principles and it is also detachable from the integrated surgical system.

The focusing objective head700includes an aspheric exit lens710having an eye-facing, concave surface711and a convex surface712opposite the concave surface. The exit lens710thus has a meniscus form. While the exit lens710shown inFIGS.9aand9bis an aspheric lens giving more design freedom, in other configurations the exit lens may be a spherical lens. Alternatively, constructing the exit lens710as a compound lens, as opposed to a singlet, allows more design freedom to optimize the optics while preserving the main characteristics of the optical system as presented here. With reference toFIG.9c, the concave surface711is characterized by a radius of curvature ry, while the convex surface712is characterized by an aspheric shape. The aspheric convex surface712in combination with the spherical concave surface711result in an exit lens710having varying thickness, with the outer perimeter edges715of the lens being thinner than the central, apex region717of the lens. The concave surface711is configured to couple to the convex surface813of the window801. In one embodiment, the exit lens710is formed of fused silica and has a refractive index nxof 1.45.

FIGS.10aand10bare schematic illustrations of components of the integrated surgical system ofFIGS.7and8functionally arranged to form an optical system1010having a first optical subsystem1001and a second optical subsystem1002that enable access to a surgical volume720in the irido-corneal angle. Each ofFIGS.10aand10binclude components of the focusing objective head700and the patient interface800ofFIG.9a. However, for simplicity, the entirety of the focusing objective head and the patient interface are not included inFIGS.10aand10b. Also, for additional simplicity inFIG.10a, the reflecting surface740ofFIGS.9aand9bis not included and the combined laser/OCT/visual beam701shown inFIG.9ais unfolded or straightened out. It is understood by those skilled in the art that adding or removing planar beam folding mirrors does not alter the principal working of the optical system formed by the first optical subsystem and the second optical subsystem.FIG.10cis a schematic illustration of a beam passing through the first optical subsystem ofFIGS.10aand10b.

With reference toFIG.10a, a first optical subsystem1001of the integrated surgical system1000includes the exit lens710of a focusing objective head700and the window801of a patient interface800. The exit lens710and the window801are arranged relative to each other to define a first optical axis705. The first optical subsystem1001is configured to receive a beam, e.g., a combined laser/OCT/visual beam701, incident at the convex surface712of the exit lens710along a second optical axis706, and to direct the beam toward a surgical volume720in the irido-corneal angle13of the eye.

During a surgical procedure, the first optical subsystem1001may be assembled by interfacing the convex surface813of the window801with the concave surface711of the exit lens710. To this end, a focusing objective head700is docked together with a patient interface800. As a result, the concave surface711of the exit lens710is coupled to the convex surface813of the window801. The coupling may be by direct contact or through a layer of index matching fluid. For example, when docking the patient interface800to focusing objective head700, a drop of index matching fluid can be applied between the contacting surfaces to eliminate any air gap that may be between the two surfaces711,813to thereby help pass the combined laser/OCT/visual beam701through the gap with minimal Fresnel reflection and distortion.

In order to direct the beam toward the surgical volume720in the irido-corneal angle13of the eye, the first optical subsystem1001is designed to account for refraction of the beam701as it passes through the exit lens710, the window801and the cornea3. To this end, and with reference toFIG.10c, the refractive index nxof the exit lens710and the refractive index nwof the window801are selected in view of the refractive index ncof the cornea3to cause appropriate beam bending through the first optical subsystem1001so that when the beam701exits the subsystem and passes through the cornea3, the beam path is generally aligned to fall within the irido-corneal angle13.

Continuing with reference toFIG.10cand beginning with the interface between the window801and the cornea3. Too steep of an angle of incidence at the interface where the combined laser/OCT/visual beam701exits the window801and enters the cornea3, i.e., at the interface between the concave surface812of the window and the convex surface of the cornea3, can create excessive refraction and distortion. To minimize refraction and distortion at this interface, in one embodiment of the first optical subsystem1001, the refractive index of the window801is closely matched to the index of the cornea3. For example, as describe above with reference toFIGS.9aand9b, the window801may have a refractive index lower than 1.42 to closely match the cornea3, which has a refractive index of 1.36.

Excessive refraction and distortion at the interface where the combined laser/OCT/visual beam701exits the window801and enters the cornea3may be further compensated for by controlling the bending of the beam701as it passed through the exit lens710and the window801. To this end, in one embodiment of the first optical subsystem1001the index of refraction nwof the window801is larger than each of the index of refraction nxof the exit lens710and the index of refraction ncof the cornea3. As a result, at the interface where the combined laser/OCT/visual beam701exits the exit lens710and enters the window801, i.e., interface between the concave surface711of the exit lens and the convex surface813of the window, the beam passes through a refractive index change from high to low that cause the beam to bend in a first direction. Then, at the interface where the combined laser/OCT/visual beam701exits the window801and enters the cornea3, i.e., interface between the concave surface812of the exit lens and the convex surface of the cornea, the beam passes through a refractive index change from low to high that cause the beam to bend in a second direction opposite the first direction.

The shape of the window801is chosen to be a meniscus lens. As such, the incidence angle of light has similar values on both surfaces812,813of the window801. The overall effect is that at the convex surface813the light bends away from the surface normal and at the concave surface812the light bends towards the surface normal. The effect is like when light passes through a plan parallel plate. Refraction on one surface of the plate is compensated by refraction on the other surface a light passing through the plate does not change its direction. Refraction at the entering, convex surface712of the exit lens710distal to the eye is minimized by setting the curvature of the entering surface such that angle of incidence β of light701at the entering surface is close to a surface normal707to the entering surface at the intersection point708.

Here, the exit lens710, the window801, and the eye1are arranged as an axially symmetric system with a first optical axis705. In practice, axial symmetry is an approximation because of manufacturing and alignment inaccuracies of the optical components, the natural deviation from symmetry of the eye and the inaccuracy of the alignment of the eye relative to the window801and the exit lens710in a clinical setting. But, for design and practical purposes the eye1, the window801, and the exit lens710are considered as an axially symmetric first optical subsystem1001.

With continued reference toFIG.10a, a second optical subsystem1002is optically coupled to the first optical subsystem1001at an angle α relative to the first optical axis705of the first optical subsystem1001. The advantage of this arrangement is that both optical subsystems1001,1002can be designed at a much lower numerical aperture compared to a system where all optical components are designed on axis with a common optical axis.

The second optical subsystem1002includes a relay lens750that, as previously described with reference toFIG.8, generates a conjugate surgical volume721of the surgical volume720within the eye. The second optical subsystem1002includes various other components collectively indicated as an optical subsystem step1003. Referring toFIG.8, these components may include a femtosecond laser source200, an OCT imaging apparatus300, a visual observation apparatus400, beam conditioners and scanners500, and beam combiners600.

The second optical subsystem1002may include mechanical parts (not shown) configured to rotate the entire subsystem around the first optical axis705of the first optical subsystem1001. This allows optical access to the whole 360-degree circumference of the irido-corneal angle13of the eye1.

With reference toFIG.10b, flexibility in arranging the first and second optical subsystems1001,1002, relative to each other may be provided by an optical assembly1004interposed between the optical output of the second optical subsystem1002and the optical input of the first optical subsystem1001. In one embodiment, the optical assembly1004may include one or more reflecting surfaces740, prisms (not shown) or optical gratings (not shown) configured to receive the optical output, e.g., combined laser/OCT/visual beam701, of the second optical subsystem1002, change or adjust the direction of the combined laser/OCT/visual beam, and direct the beam to the optical input of the first optical subsystem1001while preserving the angle α between the first optical axis705and the second optical axis706.

In another configuration, the optical assembly1004of the reflecting surfaces740further includes mechanical parts (not shown) configured to rotate741the assembly around the first optical axis705of the first optical subsystem1001while keeping the second optical subsystem1002stationary. Accordingly, the second optical axis706of the second optical subsystem1002can be rotated around the first optical axis705of the first optical subsystem1001. This allows optical access to the whole 360-degree circumference of the irido-corneal angle13of the eye1.

With considerations described above with reference toFIGS.9a,9band9c, the design of the first optical subsystem1001is optimized for angled optical access at an angle α relative to the first optical axis705of the first optical subsystem1001. Optical access at the angle α compensates for optical aberrations of the first optical subsystem1001. Table 1 shows the result of the optimization at access angle α=72 degrees with Zemax optical design software package. This design is a practical embodiment for image guided femtosecond glaucoma surgery.

This design produces diffraction limited focusing of 1030 nm wavelength laser beams and 850 nm wavelength OCT beams with numerical aperture (NA) up to 0.2. In one design, the optical aberrations of the first optical subsystem are compensated to a degree that the Strehl ratio of the first optical subsystem for a beam with numerical aperture larger than 0.15 at the irido-corneal angle is larger than 0.9. In another design, the optical aberrations of the first optical subsystem are partially compensated, the remaining uncompensated aberrations of the first optical system are compensated by the second optical subsystem to a degree that the Strehl ratio of the combined first and second optical subsystem for a beam with numerical aperture larger than 0.15 at the irido-corneal angle is larger than 0.9.

Calibration

The femtosecond laser source200, OCT imaging apparatus300, and visual observation apparatus400of the integrated surgical system1000are first individually calibrated to ensure their internal integrity and then cross-calibrated for system integrity. The essential part of system calibration is to ensure that the when the surgical focus of a laser beam201is commanded to a location of a surgical volume720, as identified by the OCT imaging apparatus and/or the visual observation apparatus400, the achieved location of the focus matches the commanded location of the focus within a certain tolerance, typically within 5 to 10 μm. Also, graphical and cursor outputs, images, overlays displayed on a user interface110, such as a computer monitor, and user inputs of ocular tissue surgical volume720locations accepted from the user interface110should correspond to actual locations in tissue within predetermined tolerances of similar accuracy.

One embodiment of this spatial calibration procedure starts with imaging calibrated scales and scaling magnifications of the OCT imaging apparatus300and/or the visual observation apparatus400and their displays in a way that the scale value on the display matches the real scale of the calibration target. Then laser calibration patterns are exposed or burned into transparent calibration targets, and the calibration patterns are subsequently imaged. Then, the intended patterns and the actual burned patterns are compared with the imaging system of the integrated surgical system1000or by a separate microscope. If they do not match within the specified tolerance, the scaling parameters of the surgical patterns are re-scaled by adjusting the scaling of the laser beam scanners. This procedure is iterated, if necessary, until all spatial calibrations are within tolerance.

Minimally Invasive Surgical Treatments

FIG.11is a three-dimensional schematic illustration of anatomical structures of the eye relevant to the surgical treatment enabled by the integrated surgical system1000. To reduce the IOP, laser treatment targets ocular tissues that affect the trabecular outflow pathway40. These ocular tissues may include the trabecular meshwork12, the scleral spur14, the Schlemm's canal18, and the collector channels19. The trabecular meshwork12has three layers, the uveal15, the corneoscleral meshwork16, and the juxtacanalicular tissue17. These layers are porous and permeable to aqueous, with the uveal15being the most porous and permeable, followed by the corneoscleral meshwork16. The least porous and least permeable layer of the trabecular meshwork12is the juxtacanalicular tissue17. The inner wall18aof the Schlemm's canal18, which is also porous and permeable to aqueous, has characteristics similar to the juxtacanalicular tissue17.

FIGS.12aand12binclude three-dimensional illustrations of a treatment pattern P1to be applied by the integrated surgical system1000to affect the surgical volume900of ocular tissue shown inFIG.11, and a two-dimensional schematic illustration of the treatment pattern P1overlaying anatomical structures to be treated.FIG.12bis essentially the same asFIG.12a, but more clearly illustrates an orthogonal relationship between the treatment pattern P1and the laser beam701.FIG.13is a three-dimensional schematic illustration of the anatomical structures of the eye including an opening902through the trabecular meshwork12that results from the application of the laser treatment pattern ofFIGS.12aand12b. The opening902may also be referred to as a channel or aperture. The opening902provides and outflow pathway40that reduces the flow resistance in the ocular tissue to increase aqueous flow from the anterior chamber7into the Schlemm's canal18and thereby reduce the IOP of the eye.

Surgical treatments reduce outflow pathway resistance while minimizing ocular tissue modification through design and selection of laser treatment patterns. A treatment pattern is considered to define a collection of a laser-tissue interaction volumes, referred to herein as cells. The size of a cell is determined by the extent of the influence of the laser-tissue interaction. When the laser spots, or cells, are spaced close along a line, the laser creates a narrow, microscopic channel. A wider channel can be created by closely spacing a multitude of laser spots within the cross section of the channel. The arrangement of the cells may resemble the arrangement of atoms in a crystal structure.

With reference toFIGS.12aand12b, a treatment pattern P1may be in the form of a cubic structure that encompasses individual cells arranged in regularly spaced rows, columns and sheets or layers. The treatment pattern P1may be characterized by x, y, z dimensions, with x, y, z coordinates of the cells being calculated sequentially from neighbor to neighbor in the order of a column location (x coordinate), a row location (y coordinate), and a layer location (z coordinate). A treatment pattern P1as such, defines a three-dimensional model of ocular tissue to be modified by a laser or a three-dimensional model of ocular fluid to be affected by a laser.

A treatment pattern P1is typically defined by a set of surgical parameters. The surgical parameters may include one or more of a treatment area A that represents a surface area or layer of ocular tissue through which the laser will travel. The treatment area A is determined by the treatment height, h, and the lateral extent of the treatment, w. A treatment thickness t that represents the level to which the laser will cut into the ocular tissue from the distal extent or border of the treatment volume at or near Schlemm's canal18to the proximal extent or border at or near the surface of the trabecular meshwork12. Thus, a laser applied in accordance with a treatment pattern may affect or produce a surgical volume that resembles the three-dimensional model of the treatment pattern, or may affect fluid located in an interior of an eye structure resembled by the three-dimensional model.

Additional surgical parameters define the placement of the surgical volume or affected volume within the eye. For example, with reference toFIGS.11,12a, and12b, placement parameters may include one or more of a location l that represents where the treatment is to occur relative to the circumferential angle of the eye, and a treatment depth d that represents a position of the three-dimensional model of ocular tissue or ocular fluid within the eye relative to a reference eye structure. In the following, the treatment depth d is shown and described relative to the region where the anterior chamber7meets the trabecular meshwork12. Together, the treatment pattern and the placement parameters define a treatment plan.

A femtosecond laser provides highly localized, non-thermal photo-disruptive laser-tissue interaction with minimal collateral damage to surrounding ocular tissue. Photo-disruptive interaction of the laser is utilized in optically transparent tissue. The principal mechanism of laser energy deposition into the ocular tissue is not by absorption but by a highly nonlinear multiphoton process. This process is effective only at the focus of the pulsed laser where the peak intensity is high. Regions where the beam is traversed but not at the focus are not affected by the laser. Therefore, the interaction region with the ocular tissue is highly localized both transversally and axially along the laser beam.

With reference toFIGS.11,12a, and12b, in accordance with embodiments disclosed herein a surgical volume900of ocular tissue to be treated is identified by the integrated surgical system1000and a treatment pattern P1corresponding to the surgical volume is designed by the integrated surgical system. Alternatively, the treatment pattern P1may be designed first, and then an appropriate surgical volume900for applying the treatment pattern may be identified. The surgical volume900of ocular tissue may comprise portions of the trabecular meshwork12and the Schlemm's canal18. For example, the surgical volume900of ocular tissue shown inFIG.11includes portions of the uveal15, the corneoscleral meshwork16, the juxtacanalicular tissue17, and the inner wall18aof the Schlemm's canal18. The treatment pattern P1defines a laser scanning procedure whereby a laser is focused at different depth locations in ocular tissue and then scanned in multiple directions to affect a three-dimensional volume of tissue comprising multiple sheets or layers of affected tissue.

With reference toFIGS.12a,12b, and13, during a laser scanning procedure, a surgical laser701may scan ocular tissue in accordance with the treatment pattern P1to form an opening902that extends from the anterior chamber7, through each of the uveal15, the corneoscleral meshwork16, the juxtacanalicular tissue17of the trabecular meshwork12, and the inner wall18aof the Schlemm's canal18. While the example opening902inFIG.13is depicted as a continuous, single lumen defining a fluid pathway, the opening may be defined an arrangement of adjacent pores forming a sponge like structure defining a fluid pathway or a combination thereof. While the example opening902inFIG.13is in the shape of a cube, the opening may have other geometric shapes.

The movement of the laser as it scans to affect the surgical volume900follows the treatment pattern P1, which is defined by a set of surgical parameters that include a treatment area A and a thickness t. The treatment area A is defined by a width w and a height h. The width may be defined in terms of a measure around the circumferential angle. For example, the width w may be defined in terms of an angle, e.g., 90 degrees, around the circumferential angle.

Referring toFIGS.11,12a, and12b, an initial placement of the laser focus within the eye is defined by a set of placement parameters, including a depth d and a location1. The location1defines a point around the circumferential angle of the eye at which laser treatment will begin, while the depth d defines a point between the anterior chamber7and the Schlemm's canal18where the laser treatment begins or ends. The depth d is measured relative to the region where the anterior chamber7meets the trabecular meshwork12. Thus, a first point that is closer to the Schlemm's canal18side of the trabecular meshwork12may be described as being deeper than a second point that is closer to the anterior chamber7side of the trabecular meshwork12. Alternatively, the second point may be described as being shallower than the first point.

With reference toFIG.13, the opening902resulting from laser application of the treatment pattern P1resembles the surgical volume900and is characterized by an area A and thickness t similar to those of the surgical volume and the treatment pattern. The thickness t of the resulting opening902extends from the anterior chamber7and through the inner wall18aof the Schlemm's canal18, while the area A defines the cross-section size of the opening902.

In accordance with embodiments disclosed herein, during a laser scanning procedure, a laser focus is moved to different depths d in ocular tissue and then scanned in two lateral dimensions or directions as defined by a treatment pattern P1to affect a three-dimensional volume900of ocular tissue comprising multiple sheets or layers of affected tissue. The two lateral dimensions are generally orthogonal to the axis of movement of the laser focus. With reference toFIG.13, the movement of a laser focus during laser scanning is described herein with reference to x, y, and z directions or axes, wherein: 1) movement of the laser focus to different depths d through the thickness t of treatment pattern P1or the volume900of tissue corresponds to movement of the focus along the z axis, 2) movement of the laser focus in two dimensions or directions orthogonal to the z axis corresponds to movement of the laser focus along the width w of the treatment pattern P1or the volume900of tissue in the x direction, and movement of the laser focus along the height h of the treatment pattern P1or the volume900of tissue in the y direction.

As used herein scanning of the laser focus generally corresponds to a raster type movement of the laser focus in the x direction, the y direction, and the z direction. The laser focus may be located at a point in the z direction and then raster scanned in two dimensions or directions, in the x direction and the y direction. The focal point of the laser in the z direction may be referred to as a depth d within the treatment pattern P1or the volume900of tissue. The two direction raster scanning of the laser focus defines a layer of laser scanning, which in turn produces a layer of laser-affected tissue.

During laser scanning, pulse shots of a laser are delivered to tissue within the volume of ocular tissue corresponding to the treatment pattern P1. Because the laser interaction volume is small, about a few micrometers (μm), the interaction of ocular tissue with each laser shot of a repetitive laser breaks down ocular tissue locally at the focus of the laser. Pulse duration of the laser for photo-disruptive interaction in ocular tissue can range from several femtoseconds to several nanoseconds and pulse energies from several nanojoules to tens of microjoules. The laser pulses at the focus, through multiphoton processes, breaks down chemical bonds in the molecules, locally photo-dissociate tissue material and create gas bubbles in wet tissue. The breakdown of tissue material and mechanical stress from bubble formation fragments the tissue and create clean continuous cuts when the laser pulses are laid down in proximity to one another along geometrical lines and surfaces.

Table 2 includes examples of treatment pattern parameters and surgical laser parameters for treating tissue. The range of the parameter set is limited by practical ranges for the repetition rate of the laser and the scanning speed of the scanners.

With reference toFIGS.11,12a,12b,13,14aand14b, in one type of laser scanning procedure, the scanning begins at the end of the treatment pattern P1adjacent the anterior chamber7and proceeds in a direction that generally corresponds to the direction of propagation of the laser beam701. More specifically, and with reference toFIG.14a, the laser scanning proceeds in the z direction toward an anatomical structure, e.g., the inner wall18aof the Schlemm's canal18, while the direction of propagation of the laser701also proceeds toward same anatomical structure, e.g., the inner wall18aof the Schlemm's canal18.

Laser scanning in this manner, however, may be ineffective at producing the desired opening902between the anterior chamber7and the Schlemm's canal18due to interference by gas bubbles produced during laser application. As noted above, femtosecond lasers generate a very short pulse of optical energy. When a beam of such pulses is focused to a very small volume of space characterized by a small cross-sectional area, a non-linear effect occurs within the focus spot. When such a focus spot is directed onto tissue, the tissue is photodisrupted (broken down) leaving a small bubble of gas. This process is essentially non-thermal and requires a tiny amount of energy. The result is that the surrounding tissue is not affected.

However, when a femtosecond laser beam is scanned over the surface of a tissue, the laser treatment of this initial surface layer generates a layer of bubbles over the area of the treatment. When the laser scans the layer of tissue below or deeper than the initial surface layer, these bubbles create a shadow effect that scatters the incident laser light, effectively blocking further treatment of the tissue. This renders further laser treatment of tissue beneath or deeper that the initial surface layer ineffective.

An example of this effect within the context of glaucoma surgery is illustrated inFIGS.14aand14b. InFIG.14a, the focus of the laser beam701is initially located at a depth d1. This depth d1places the laser focus in an initial layer904of tissue. For example, initial layer904of tissue may be at the interface between the uveal15of the trabecular meshwork12and the anterior chamber7. In this instance, this depth location of the laser focus is referred to a null depth and the initial layer904to be treated corresponds to the surface of the uveal15facing the anterior chamber7. Once the laser focus is positioned at the initial depth d1, the focus is scanned in multiple directions while being maintained at the initial depth. With reference toFIG.14a, the multiple directions are the x direction and y direction, where the x direction is into the plane ofFIG.14a.

With reference toFIG.14b, the raster scanning in the multiple directions results in the photodisruption of the initial layer904of tissue and the formation of a layer of bubbles906at the initial layer of tissue. The focus of the laser beam701is then moved in the z direction toward the inner wall18aof the Schlemm's canal18to another depth d2. This depth d2places the laser focus at a subsequent layer908of tissue deeper than the initial layer904. For example, the deeper layer of tissue may comprise the uveal15of the trabecular meshwork12. Once the laser focus is positioned at the subsequent layer908, the focus is raster scanned in multiple directions while being maintained at that depth. However, in this instance, the layer of bubbles906scatters the incident laser light, effectively blocking further treatment of the tissue at the subsequent layer908.

With reference toFIGS.11,12a,12b,13,15a-15g, in accordance with embodiments disclosed the above ineffective laser treatment is avoided by implementing a laser scanning procedure, whereby the laser scanning begins at the end of the treatment pattern P1adjacent the Schlemm's canal18and proceeds in a direction generally opposite to or against the direction of propagation of the laser beam701. More specifically, and with reference toFIG.15a, the laser scanning starts at an anatomical structure, e.g., the inner wall18aof the Schlemm's canal18and proceeds away from that structure in the z direction toward the anterior chamber7, while the direction of propagation of the laser beam701proceeds toward the that structure.

With this scanning procedure, the laser beam of femtosecond pulses is focused within a volume of ocular tissue at an initial depth or distance from a surface of the volume of tissue. An initial layer of tissue at the initial depth is treated, which generates a layer of bubbles at the area of the initial layer. After treatment of the initial layer of tissue, the laser is refocused to a subsequent layer of tissue that is shallower than the initial layer of tissue, i.e., at a depth that is closer to the surface of the volume of ocular tissue than the initial depth. Since the layer of bubbles at the area of the initial layer is below the second layer, the bubbles do not obstruct the second layer. This process is repeated until the laser scans, layer-by-layer through the volume of ocular tissue to the surface of the volume of tissue.

An example of this scanning procedure within the context of glaucoma surgery is illustrated inFIGS.15a-15g. InFIG.15a, the focus of the laser beam701is initially located at a depth d1. This depth d1places the laser focus in an initial layer910of tissue. For example, initial layer910of tissue may comprise the inner wall18aof the Schlemm's canal18. Once the laser focus is positioned at the initial depth d1, the focus is scanned in multiple directions while being maintained at the initial depth d1. With reference toFIG.15a, the multiple directions are the x direction and y direction, where the x direction is into the plane ofFIG.15a.

With reference toFIG.15b, the laser scanning in multiple directions results in the photodisruption of the initial layer910of tissue and the formation of a layer of bubbles912at the location of the initial layer of tissue. The focus of the laser beam701is then moved in the z direction toward the anterior chamber7to a subsequent depth d2. The subsequent depth d2places the laser focus at a subsequent layer914of tissue less deep than the initial layer910of tissue. For example, the subsequent layer914of tissue may comprise a portion of the inner wall18aof the Schlemm's canal18, the juxtacanalicular tissue17, and the corneoscleral meshwork16. Once the laser focus is positioned at the subsequent depth d2, the focus is scanned in multiple directions while being maintained at the subsequent depth d2. Since the layer of bubbles912is beneath the subsequent layer914, the bubbles do not obstruct laser access to or block photodisruption of the subsequent layer.

With reference toFIG.15c, the laser scanning in multiple directions results in the photodisruption of the subsequent layer914of tissue and the formation of a layer of bubbles916at the location of the subsequent layer of tissue. The focus of the laser beam701is then moved in the z direction toward the anterior chamber7to a subsequent depth d3. The subsequent depth d3places the laser focus at a subsequent layer918of tissue less deep than the subsequent layer914of tissue. For example, the subsequent layer914of tissue may comprise a portion of the juxtacanalicular tissue17and the corneoscleral meshwork16. Once the laser focus is positioned at the subsequent depth d3, the focus is scanned in multiple directions while being maintained at the subsequent depth d3. Since the layers of bubbles912,916are beneath the subsequent layer918, the bubbles do not obstruct laser access to or block photodisruption of the subsequent layer.

With reference toFIG.15d, the laser scanning in multiple directions results in the photodisruption of the subsequent layer918of tissue and the formation of a layer of bubbles920at the location of the subsequent layer of tissue. The focus of the laser beam701is then moved in the z direction toward the anterior chamber7to a subsequent depth d4. The subsequent depth d4places the laser focus at a subsequent layer922of tissue less deep than the subsequent layer918of tissue. For example, the subsequent layer922of tissue may comprise a portion of the corneoscleral meshwork16and the uveal15. Once the laser focus is positioned at the subsequent depth d4, the focus is scanned in multiple directions while being maintained at the subsequent depth d4. Since the layers of bubbles912,916,920are beneath the subsequent layer922, the bubbles do not obstruct laser access to or block photodisruption of the subsequent layer.

With reference toFIG.15e, the laser scanning in multiple directions results in the photodisruption of the subsequent layer922of tissue and the formation of a layer of bubbles924at the location of the subsequent layer of tissue. The focus of the laser beam701is then moved in the z direction toward the anterior chamber7to a subsequent depth d5. The subsequent depth d5places the laser focus at a subsequent layer926of tissue less deep than the subsequent layer922of tissue. For example, the subsequent layer926of tissue may comprise the uveal15. Once the laser focus is positioned at the subsequent depth d5, the focus is scanned in multiple directions while being maintained at the subsequent depth d5. Since the layers of bubbles912,916,920,924are beneath the subsequent layer926, the bubbles do not obstruct laser access to or block photodisruption of the subsequent layer.

With reference toFIG.15f, the laser scanning in multiple directions results in the photodisruption of the subsequent layer926of tissue and the formation of a layer of bubbles928at the location of the subsequent layer of tissue. The focus of the laser beam701is then moved in the z direction toward the anterior chamber7to a subsequent depth d6. The subsequent depth d6places the laser focus at a subsequent layer930of tissue less deep than the subsequent layer926of tissue. For example, the subsequent layer930of tissue may comprise the uveal15and the inner surface of the uveal facing the anterior chamber7. Once the laser focus is positioned at the subsequent depth d6, the focus is scanned in multiple directions while being maintained at the subsequent depth d6. Since the layers of bubbles912,916,920,924,928are beneath the subsequent layer930, the bubbles do not obstruct laser access to or block photodisruption of the subsequent layer.

With reference toFIG.15g, the laser scanning in multiple directions results in the photodisruption of the subsequent layer930of tissue and the formation of a layer of bubbles932at the location of the subsequent layer of tissue. Photodisruption of this subsequent layer930of tissue results in the formation of an opening902between the anterior chamber7and the Schlemm's canal18, thus completing the laser treatment procedure.

With reference toFIG.16a, upon completion of the laser scanning the opening902may be partially obstructed or occluded by the gas bubbles912,916,920,924,928created during treatment. Thus, in accordance with embodiments disclosed herein, the direction of the laser scanning described with reference toFIGS.15a-15gmay be reversed in order to push any remaining bubbles into the Schlemm's canal18thereby clearing the opening902, as shown inFIG.16b.

FIG.17is a flowchart of a method of treating a target volume of ocular tissue with a laser having a direction of propagation toward the target volume of ocular tissue. With reference toFIGS.12aand12b, the target volume60of ocular tissue is characterized by a distal extent62, a proximal extent64, and a lateral extent66. The distal extent62corresponds to the part or point of the target volume60that is most distal along the direction of propagation of the laser beam701. The proximal extent64corresponds to the part or point of the target volume60that is most proximal along the direction of propagation of the laser beam701. The lateral extent66corresponds to the distance or width w of the target volume60along the circumference angle.

The method, which may be performed by the integrated surgical system1000ofFIGS.7-10b, begins at a point in a surgical procedure where access to the irido-corneal angle has already been obtained and the target volume60of ocular tissue has already been identified for treatment. Systems and methods for accessing the irido-corneal angle are described in U.S. patent application Ser. No. 16/036,883, entitled Integrated Surgical System and Method for Treatment in the Irido-Corneal Angle of the Eye, the disclosure of which is hereby incorporated by reference. Systems and method for identifying volumes of ocular tissue for treatment and designing treatment patterns reference are described in U.S. patent application Ser. No. 16/125,588, entitled Non-Invasive and Minimally Invasive Laser Surgery for the Reduction of Intraocular Pressure in the Eye, the disclosure of which is hereby incorporated by reference.

At block1702, the integrated surgical system1000initially photodisrupts tissue at an initial depth d1corresponding to the distal extent62of the target volume60of ocular tissue is. To this end, and with reference toFIG.15a, the integrated surgical system1000focuses light from a femtosecond laser beam701at a spot in the tissue at the initial depth d1and applies optical energy to the tissue, which energy is at a level sufficient to photodisrupt the tissue. Optical energy is applied by scanning the laser beam701in multiple directions defining an initial treatment plane910at the initial depth d1to thereby photodisrupt an initial layer of tissue of the target volume of ocular tissue. With reference toFIG.13, the scanning may be in the form of a raster scan where the laser is scanned in a first direction along the lateral extent66, i.e., the x direction, and then slightly repositioned in a second direction. i.e., the y direction, and then scanned again along the lateral extent.

As an additional aspect of the initial photodisruption process of block1702, the integrated surgical system1000may detect the distal extent62of the target volume of ocular tissue. To this end, in one configuration images captured by the OCT imaging apparatus300are processed by the control system100to detect the distal extent62of the target volume using known techniques. In another configuration, the integrated surgical system1000may include a multiphoton imaging apparatus (not shown) that provides a visual indication on a display of the user interface110that is indicative of the location of the focus of the laser beam701relative to the distal extent62of the target volume60of ocular tissue. The integrated surgical system1000may also determine the lateral extent66of the target volume60of ocular tissue based on OCT imaging.

At block1704and with reference toFIGS.15b-15f, the integrated surgical system1000subsequently photodisrupts tissue at one or more subsequent depths d2-d6between the distal extent62of the target volume60of ocular tissue and the proximal extent64of the target volume of ocular tissue is by moving a focus of the laser beam701in a direction opposite the direction of propagation of the laser. To this end, the integrated surgical system1000focuses light from a femtosecond laser beam701at a spot in the tissue at the one or more subsequent depths d2-d6and applies optical energy to the tissue, which energy is at a level sufficient to photodisrupt the tissue. Optical energy is applied by scanning the laser beam701in multiple directions defining a subsequent treatment plane914,918,922,926,930at a respective different depth d2-d6, to thereby photodisrupt one or more subsequent layers of tissue of the target volume60of ocular tissue. With reference toFIG.13, the scanning may be in the form of a raster scan where the laser is scanned in a first direction along the lateral extent66, i.e., the x direction, and then slightly repositioned in a second direction. i.e., the y direction, and then scanned again along the lateral extent.

As an additional aspect of the subsequent photodisruption process of block1704, the integrated surgical system1000may detect the proximal extent64of the target volume60of ocular tissue. To this end, in one configuration images captured by the OCT imaging apparatus300are processed by the control system100to detect the proximal extent64of the target volume60using known techniques. In another configuration, the integrated surgical system1000may include a multiphoton imaging apparatus (not shown) that provides a visual indication on a display of the user interface110that is indicative of the location of the focus of the laser beam701relative to the proximal extent64of the target volume60of ocular tissue. In yet another configuration, the integrated surgical system1000may include an opto-mechanical imaging apparatus (not shown) that provides a visual indication on a display of the user interface110that is indicative of the location of the focus of the laser beam701relative to the proximal extent64of the target volume60of ocular tissue.

At block1706, the integrated surgical system1000determines if the proximal extent64of the target volume60of ocular tissue has been photodisrupted. If the proximal extent64has not been photodisrupted, the process return to block1704and the integrated surgical system1000repeats the photodisrupting at one or more subsequent depths until tissue at the proximal extent64of the target volume60of ocular tissue is photodisrupted.

Returning to block1706and with reference toFIG.16a, if the proximal extent64has been photodisrupted, the process proceeds to block1708and the integrated surgical system1000photodisrupts tissue debris or bubbles906between the proximal extent64of the target volume60of ocular tissue and the distal extent62of the target volume by moving the focus of the laser beam701in the direction of propagation of the laser. To this end, the integrated surgical system1000focuses light from a femtosecond laser beam701at a spot in the volume of tissue debris or bubbles906at the one or more subsequent depths and applies optical energy to the tissue debris or bubbles. Optical energy is applied by scanning the laser beam701in multiple directions along one or more of the previously-scanned treatment planes910,914,918,922,926,930to photodisrupt tissue debris or bubbles906between the proximal extent64and the distal extent62of the photodisrupted target volume60.

At block1710, the integrated surgical system1000may determine to repeat the treatment of the photodisrupted target volume60of ocular tissue or to end the treatment. If treatment is repeated, the process returns to block1702, where the integrated surgical system1000repeats the initial photodisrupting of tissue, and then proceeds to blocks1704and1706, where the system repeats the subsequent photodisrupting of tissue one or more times. If treatment is not to be repeated, the process proceeds to block1712, where treatment ends.

Regarding the use of a multiphoton imaging apparatus to detect the distal extent62of the target volume of ocular tissue, or the proximal extent64of the target volume, such an apparatus is configured to present an image of a second harmonic light that results from an encounter between the focus of the laser beam701and tissue. When the focus of the laser beam701is not encountering tissue, the intensity of the second harmonic light is zero or very low. When the focus is encountering tissue, the intensity of the second harmonic light increases. Based on this, a distal extent62such as shown inFIGS.12aand12bmay be detected by first advancing the focus of the laser beam701through the trabecular meshwork12and the inner wall18aof the Schlemm's canal and into the Schlemm's canal18, where the focus will not encounter light and the intensity of the second harmonic light is zero or very low, and then retracting the focus back toward the inner wall18aof the Schlemm's canal and detecting that the focus is at the inner wall when an increase in the intensity of the second harmonic light is noted on the display.

Regarding the use of an opto-mechanical imaging apparatus to detect the proximal extent64of the target volume60of ocular tissue, such an apparatus is configured to direct a first beam of light and a second beam of light to be incident with the target volume and to align the first beam of light and the second beam of light relative to each other and relative to the laser beam such that the first beam of light and the second beam light intersect at a point corresponding to the focus of the laser. The apparatus is also configured to capture an image of a first spot corresponding to the first beam of light, and a second spot corresponding to the second beam of light relative to the proximal extent64of the target volume60of ocular tissue. The first and second spots appear in the image as two separate visible spots on the surface of the proximal extent64when the focus is away from the surface, and as a single, overlapping spot when the focus is on the surface. Accordingly, the proximal extent64is detected when the spots overlap.

With reference toFIGS.7-10b, a surgical system1000for implementing the method ofFIG.17includes a first optical subsystem1001and a second optical subsystem1002. The first optical subsystem1001includes the exit lens710of a focusing objective head700and the window801of a patient interface800. The second optical subsystem1002including a laser source200configured to output a laser beam201/701and a plurality of components1003configured to one or more of focus, scan, and direct the laser beam through the focusing objective head, in a direction of propagation toward the target volume of ocular tissue.

The surgical system1000further includes a control system100coupled to the second optical subsystem1002and configured to control the focus and scan of the laser beam701to photodisrupt tissue at an initial depth corresponding to the distal extent of the target volume of ocular tissue. To this end, the control system100is configured to focus light from a femtosecond laser source200at a spot in the tissue at the initial depth and then apply optical energy to the tissue, where the energy is sufficient to photodisrupt tissue. The control system100controls the focus and scan of the laser beam701during application of optical energy by being further configured to scan the laser in multiple directions defining an initial treatment plane, to thereby photodisrupt an initial layer of tissue of the target volume of ocular tissue.

The control system100is also configured to control the focus and scan of the laser beam701to photodisrupt tissue at one or more subsequent depths between the distal extent of the target volume of ocular tissue and the proximal extent of the target volume of ocular tissue by moving a focus of the laser in a direction opposite the direction of propagation of the laser. To this end, the control system100is configured to focus light from a femtosecond laser source200at a spot in the tissue at a subsequent depth and then apply optical energy to the tissue, where the energy is sufficient to photodisrupt tissue. The control system100controls the focus and scan of the laser beam701during application of optical energy by being further configured to scan the laser in multiple directions defining a subsequent treatment plane, to thereby photodisrupt a subsequent layer of tissue of the target volume of ocular tissue.

The control system100is also configured to control the focus and scan of the laser beam701to photodisrupt tissue debris or bubbles between the proximal extent of the target volume of ocular tissue and the distal extent of the target volume by moving the focus of the laser in the direction of propagation of the laser, after photodisrupting the target volume of ocular tissue. The control system100is further configured to control the focus and scan of the laser beam701to repeat the initial photodisrupting of tissue and the subsequent photodisrupting of tissue one or more times.

FIG.18is a flowchart of a method of treating an eye comprising an anterior chamber, a Schlemm's canal, and a trabecular meshwork therebetween. The method, which may be performed by the integrated surgical system1000ofFIGS.7-10b, begins at a point in a surgical procedure where access to the irido-corneal angle has already been obtained and one or more anatomical structures of the eye that are to be treated have been located.

At block1802and with reference toFIGS.15aand15b, the integrated surgical system1000initially photodisrupts ocular tissue at or near an interface of an inner wall18aof the Schlemm's canal18and the trabecular meshwork12. To this end, the integrated surgical system1000focuses light from a femtosecond laser beam701at a spot in the ocular tissue at or near the interface of the inner wall18aof the Schlemm's canal18and the trabecular meshwork12and applies optical energy to the tissue, which energy is at a level sufficient to photodisrupt the tissue.

As an additional aspect of the initial photodisruption process of block1802, the integrated surgical system1000may detect ocular tissue at or near the interface of the inner wall18aof the Schlemm's canal18and the trabecular meshwork12. To this end, in one configuration images captured by the OCT imaging apparatus300are processed by the control system100to detect the interface of the inner wall18aof the Schlemm's canal18and the trabecular meshwork12using known techniques. In another configuration, the integrated surgical system1000may include a multiphoton imaging apparatus (not shown) that provides a visual indication on a display of the user interface110that is indicative of the location of the focus of the laser beam701relative to the interface of the inner wall18aof the Schlemm's canal18and the trabecular meshwork12. The integrated surgical system1000may also determine a lateral extent66of ocular tissue to be photodisrupted based on OCT imaging.

At block1804and with reference toFIGS.15c-15f, the integrated surgical system1000subsequently photodisrupts ocular tissue of the trabecular meshwork12. To this end, the integrated surgical system1000focuses light from a femtosecond laser beam701at a spot in tissue of the trabecular meshwork12and applies optical energy to the tissue, which energy is at a level sufficient to photodisrupt the tissue.

As an additional aspect of the subsequent photodisruption process of block1804, the integrated surgical system1000may detect a proximal extent of tissue of the trabecular meshwork. To this end, in one configuration images captured by the OCT imaging apparatus300are processed by the control system100to detect the proximal extent64of the tissue of the trabecular meshwork using known techniques. In another configuration, the integrated surgical system1000may include a multiphoton imaging apparatus (not shown) that provides a visual indication on a display of the user interface110that is indicative of the location of the focus of the laser beam701relative to the proximal extent64of the tissue of the trabecular meshwork. In yet another configuration, the integrated surgical system1000may include an opto-mechanical imaging apparatus (not shown) that provides a visual indication on a display of the user interface110that is indicative of the location of the focus of the laser beam701relative to the proximal extent64of the tissue of the trabecular meshwork.

At block1806, the integrated surgical system1000determines if an opening is formed between the anterior chamber and the Schlemm's canal. If an opening has not been formed, the process return to block1802and the integrated surgical system1000repeats the initial photodisrupting of ocular tissue and then proceeds to block1804and repeats the subsequent photodisrupting of ocular tissue one or more times until an opening is formed between the anterior chamber and the Schlemm's canal. If an opening has been formed, the process proceeds to block1808, where treatment ends.

With reference toFIGS.7-10b, a surgical system1000for implementing the method ofFIG.18includes a first optical subsystem1001and a second optical subsystem1002. The first optical subsystem1001includes the exit lens710of a focusing objective head700and the window801of a patient interface800. The second optical subsystem1002including a laser source200configured to output a laser beam201/701and a plurality of components1003configured to one or more of focus, scan, and direct the laser beam through the focusing objective head, in a direction of propagation toward the target volume of ocular tissue.

The surgical system1000further includes a control system100coupled to the second optical subsystem1002and configured to control the focus and scan of the laser beam701to initially photodisrupt ocular tissue at or near an interface of an inner wall of the Schlemm's canal and the trabecular meshwork. To this end, the control system100is configured to focus light from a femtosecond laser source200at a spot in the ocular tissue at or near the interface of the inner wall of the Schlemm's canal and the trabecular meshwork, and then apply optical to the tissue, where the energy is sufficient to photodisrupt tissue.

The control system100is also configured to control the focus and scan of the laser beam701to subsequently photodisrupt tissue of the trabecular meshwork. To this end, the control system100is configured to focus light from a femtosecond laser at a spot in tissue of the trabecular meshwork, and then apply optical energy to the tissue, where the energy is sufficient to photodisrupt tissue. The control system100is further configured to control the focus and scan of the laser beam701to repeat the initial photodisrupting of ocular tissue and the subsequent photodisrupting of ocular tissue one or more times until an opening is formed between the anterior chamber and the Schlemm's canal.

With reference toFIGS.19and20, as previously described, a 3D treatment pattern P1may be defined by a number of 2D treatment layers1902or treatment planes that are stacked to form a 3D treatment pattern characterized by a width w, height h, and depth or thickness t. Each individual treatment layer1902is in turn characterized by a pattern height h (equal to the height h of the 3D treatment pattern P1) and a pattern width w (equal to the width w of the 3D treatment pattern P1) and comprises an array of spots1904spaced apart to establish or fit within the height and width. The pattern width w corresponds to a distance along the circumference of the corneal angle parallel to the trabecular meshwork. This direction is also known as the circumferential direction. The pattern height h corresponds to a distance transverse to the circumference of the corneal angle perpendicular to the trabecular meshwork. This direction is also known as the azimuthal direction.

Each spot1904in the treatment pattern P1corresponds to a site within a target volume of ocular tissue where optical energy is applied at a laser focus to create a micro-photodisruption site. With reference toFIG.20, each spot1904in a treatment layer1902is separated from a neighboring spot by programmable distances called spot separation (Spot Sep) and a line separation (Line Sep). A treatment layer1902is completed with the programmed pattern width w and pattern height h is achieved. Each layer1902in the 3D treatment pattern P1is separated from a neighboring layer by a layer separation (Layer Sep).

A treatment pattern P1may be defined by a set of programmable parameters, such as shown in Table 3.

Other, non-rectangular and more irregular treatment patterns can also be programmed and created in the tissue. These irregular patterns can still be decomposed to spots, lines, and layers and their extent characterized by width, height, and depth. Examples of irregular treatment patterns are described in U.S. patent application Ser. No. 16/838,858, entitled Method, System, and Apparatus for Generating Three-Dimensional Treatment Patterns for Laser Surgery of Glaucoma, the disclosure of which is hereby incorporated by reference.

In one embodiment of laser treatment, such as described above with reference toFIGS.15a-15g, each treatment layer1902is individually created by scanning the laser focus in two dimensions, e.g., width and height, or z and y, to the various spots1904defining the layer, while the focus is fixed at the third dimension, e.g., depth or Z. Once a treatment layer1902is created, the focus is moved in the depth or z direction and the next treatment layer in the stack is created. This process is repeated until all treatment layers1902in the 3D treatment pattern P1are created.

Patient Customized Laser Treatment

As noted previously in this disclosure, femtosecond laser pulses treat tissue by a process called photodisruption in which tissue at the focus of a beam is disrupted to elemental gas. The intent of treating the tissue in this manner is to create or cut an aperture, opening, or channel through ocular tissue, and through which the intraocular pressure can be reduced. The “cutting efficiency” of a laser treatment is a function of laser fluence, which is the ratio of energy per pulse to the area over which the energy is delivered. The area over which the energy is delivered is referred to as a laser focus spot size. Once the laser fluence exceeds a breakdown threshold value, the tissue within a volume specified by the laser focus spot size is disrupted. If the laser fluence is less than the breakdown threshold, the focused laser does not affect the tissue. It is generally accepted that the breakdown threshold for ocular tissue is approximately 0.8 to 1.0 μJ/cm2.

In embodiments disclosed herein, femtosecond lasers treat the trabecular meshwork by focusing a beam of a femtosecond laser pulse through optics of a focusing objective head and a window of a patient interface, through the cornea, through the anterior chamber, and into a spot on the iridocorneal angle. The size (diameter) of the laser focus spot changes depending upon the number of optical aberrations introduced into the beam trajectory as it enters, and passes through the optics of the focusing objective head, the window of the patient interface, and the eye to the trabecular meshwork12. The location of the trabecular meshwork12varies across the patient population due to anatomical differences in corneal anterior and posterior shape, corneal thickness, and corneal diameter. There is a unique beam trajectory for each patient, which leads to a unique set of optical aberrations. Therefore, there is variation in laser focus spot size across the patient population—and for a fixed energy—a different fluence, resulting in variation in cutting efficiency.

Disclosed herein are methods and systems that create homogeneous cutting efficiency across a patient population by combining biometric data, an anatomical model, and laser control to customize the delivery of laser energy to each patient. In some embodiments, the laser energy used to treat tissue in the irido-corneal angle is adjusted based on the optical anatomy of the eye. This laser energy adjustment is intended to compensate for the change in laser fluence resulting from optical aberrations of the eye, and optical and mechanical aberrations introduced by components of the laser treatment system, e.g., the optics of the focusing objective head and the window of the patient interface.

Disclosed laser treatment methods and systems deliver laser energy to optical tissue at energy levels that vary as a function of the location of the tissue being treated. For example, an energy delivery look up table may provide laser energy levels as a function of the location of a laser focus in a volume of ocular tissue in the irido-corneal angle of the eye, thereby enabling adjustments of laser energy during treatment.

Other disclosed methods and systems generate a laser energy delivery look up table that may be employed by the laser treatment methods and systems. These methods and systems generate look up tables based on simulated biometric data across a simulated patient population and use a graphics rendering model, such as a ray tracing model, to obtain spot size distributions for the laser focus at different simulated locations in anatomy of the eye. Energy levels may be assigned to different focus locations based on a respective spot size associated with the focus at the different locations.

Patient Biometric Data

With reference toFIG.21, which is a schematic illustration of a cornea of a left eye, the disclosed methods and systems may be based on biometric data, including various natural anatomical measurements of the eye and demographic data, e.g., patient age. “Natural” in this context means that the anatomical measurements of the eye are obtained without imparting deformation to the eye. For example, coupling a patient interface800to the eye, as shown inFIG.9a, deforms the cornea. Accordingly, the natural anatomical measurements described herein are obtained in the absence of a coupling of a patient interface800.

With continued reference toFIG.21, the natural anatomical measurements may include one or more sets of measurements obtained relative to one or more meridians of the cornea3. The meridians of the cornea3may be described in terms of clock time, and include for example, a 3-9 o'clock meridian2124(also referred to as a nasal-temporal meridian), and a 6-12 o'clock meridian2126(also referred to as a superior-inferior meridian). Numerous other meridians of the cornea3at respective clock times are present around the circumference of the cornea, however, for clarity of illustration only the nasal-temporal meridian2124and the superior-inferior meridian2126are shown inFIG.21.

Natural anatomical measurements include:1) the central corneal thickness (CCT)2102of the cornea3, which corresponds to the difference in height between the anterior surface2120of the cornea and the posterior surface2122of the cornea at the apex2118of the cornea;2) one or more white-to-white diameters (W2W), which may include for example, a nasal-temporal W2W diameter (W2Wnt)2104along a nasal-temporal meridian2124, or a superior-inferior W2W diameter (W2Wsi)2106along a superior-inferior meridian2126, or a W2W diameter for any other meridian of the cornea3;3) one or more anterior cornea radii of curvature (Ra), which may include for example, a nasal-temporal anterior cornea radius of curvature (Rant)2112along a nasal-temporal meridian2124, or a superior-inferior anterior cornea radius of curvature (Rasi)2114along a superior-inferior meridian2126, or an anterior cornea radius of curvature (Ra) for any other meridian of the cornea3;4) one or more posterior cornea radii of curvature (Rp), which may include for example, a nasal-temporal posterior cornea radius of curvature (Rpnt)2108derived from a nasal-temporal anterior cornea radius of curvature (Rant)2112, or a superior-inferior posterior cornea radius of curvature (Rpsi)2110, derived from a superior-inferior anterior cornea radius of curvature (Rasi)2114, or a posterior cornea radius of curvature (Rp) for any other meridian of the cornea3, each of which is derived from a corresponding anterior cornea radius of curvature (Ra).

The natural anatomical measurements may be obtained using measurement equipment that is commonly found in ophthalmic settings such as the IOLMaster or the Orbscan. Germane biometric data that these devices calculate are the CCT2102, the anterior cornea radius of curvature Ra along numerous meridians of the cornea (including but not limited to the nasal-temporal anterior cornea radius of curvature (Rant)2112and the superior-inferior anterior cornea radius of curvature (Rasi)2114), and the W2W diameter along numerous meridians of the cornea (including but not limited to the nasal-temporal W2W diameter (W2Wnt)2104and the superior-inferior W2W diameter (W2Wsi)2106).

The natural posterior cornea radii of curvature Rp may be derived from the anterior cornea radius of curvature Ra using a known relationship. For example, the ratio of the anterior-to-posterior radius of curvature has been comprehensively measured in the literature and is a stable relationship regardless of age, gender, or race. See, e.g., M. Dubbelman, V.A.D.P Sicam, and G. L. Van der Heijde, “The shape of the anterior and posterior surface of the aging human cornea,”Vision Research(2006) 46, 993-1001. The ratio of the natural anterior radius of curvature Ra to the natural posterior radius of curvature Rp is approximately 1.22. Accordingly, a natural posterior cornea radius of curvature Rp may be derived using the following equation:
Rp=Ra/1.22  (Eq. 1)

With continued reference toFIG.21, regarding the anterior cornea radii of curvature and the posterior cornea radii of curvature, because the anterior surface2120of the cornea3and the posterior surface2122of the cornea are aspherical the respective radii of curvature of these surfaces varies from point to point on the surface. For example, considering the cross-section of the cornea3along the nasal-temporal meridian2124shown inFIG.21, the measures of Rant2112and Rpnt2108vary from point to point along the arc of the cross-section. Similarly, the measures of Rasi2114and Rpsi2110vary along the arc of the cross-section of the cornea3along the superior-inferior meridian2126. Furthermore, the anterior surface2120of the cornea3and the posterior surface2122of the cornea have different shapes, with the posterior surface curving more sharply than the anterior surface.

Other biometric data of the patient includes an age-based posterior conic constant (k)2116. The age-based posterior conic constant (k) mathematically describes the deviation of the posterior surface2122of the cornea3from a purely spherical surface. The age-based posterior conic constant (k) is determined from an empirical relationship determined from clinical data and is a function of patient age. This relationship is given as:
k=1−1.01(±0.04)−0.0062(±0.0009)*Age  (Eq. 2)

Having thus described the types of biometric data relevant to the methods and system disclosed herein, a description of a method and system of laser treatment of a patient based on the biometric data of that particular patient follows.

Laser Treatment

FIG.22is a flowchart of a method of photodisrupting a target volume of ocular tissue with a laser, wherein laser energy may vary as a function of the location of the target volume of ocular tissue, and the location of the laser focus within the target volume. The target volume of ocular tissue may be located in an irido-corneal angle of an eye of a patient, at a location along or around the circumference of the irido-corneal angle. The method begins at a point in a surgical procedure where access to the irido-corneal angle has already been obtained and one or more anatomical structures of the eye that are to be treated have been located. The target volume of ocular tissue may be entirely within ocular tissue. Alternatively, at least a portion of the target volume of ocular tissue may encompass portions of adjacent anatomy, e.g., the anterior chamber, or the interior of the Schlemm's canal.

The method ofFIG.22may be performed by the integrated surgical system1000ofFIGS.7-10b, having a control system100further configured as shown inFIG.23. The control system100includes an anatomical anchor locator2304, a treatment plan module2310, and an energy control module2302. The energy control module2302is configured to control the energy level of the laser during treatment. The energy control module2302may include, for example, a look up table2324that maps coordinate locations within a target volume of ocular tissue to one or more energy parameters. The anatomical anchor locator2304is configured to determine a coordinate set2306corresponding to the location of an anatomical anchor of the patient based on a set of patient data2308and a set of optics data2309. This determined coordinate set2306is used to position the laser focus at an initial location within the target volume of ocular tissue. Once positioned at the initial location, further movement of the laser focus through the target volume of ocular tissue is controlled by the treatment plan module2310, which defines a treatment pattern through which a laser focus is scanned in order to treat the target volume of ocular tissue. As further described below, the treatment pattern is defined by a plurality of coordinate sets2306,2312that include the coordinate set2306corresponding to the location of an anatomical anchor.

Prior to initiation of the method ofFIG.22, patient data2308, including natural biometric data and demographic data of the patient being treated, and optics data2309, may be input to the control system100through a user interface110, together with a treatment plan for the patient. As described above with reference toFIGS.12aand12b, a treatment plan may be defined by a treatment pattern P1that defines the geometry of the target volume of ocular tissue to be treated, and placement parameters that define the location of the target volume of ocular tissue around the circumference of the irido-corneal angle.

Regarding the treatment pattern, with additional reference toFIG.19, the treatment plan module2310may define a 3D treatment pattern P1having a number of 2D treatment layers1902or treatment planes that are stacked to form a 3D treatment pattern characterized by a width w, height h, and depth or thickness t. Each individual treatment layer1902is in turn characterized by a pattern height h (equal to the height h of the 3D treatment pattern P1) and a pattern width w (equal to the width w of the 3D treatment pattern P1) and comprises an array of spots1904—each at a corresponding one of the plurality of coordinate sets2306,2312. Treatment patterns of various geometric shapes may be defined by the treatment plan module2310. Examples of other treatment patterns are described in U.S. patent application Ser. No. 16/838,858, entitled Method, System, and Apparatus for Generating Three-Dimensional Treatment Patterns for Laser Surgery of Glaucoma.

Returning toFIG.22, at block2202, and with additional reference toFIGS.23,24, and25, a focus2402of a laser201is placed at an initial location2408within the target volume of ocular tissue2404that is associated with an eye of a patient. To this end, the anatomical anchor locator2304ofFIG.23derives a coordinate set2306corresponding to the initial location2408of the focus2402within the target volume of ocular tissue2404ofFIG.24. This initial coordinate set2306may be expressed, for example in cylindrical coordinates (ρ, θ, y(θ)), and is derived based on patient data2308, including natural biometric data and demographic data of the patient being treated, and optics data2309. Once the coordinate set2306for the initial location of the focus2402is derived, the focus is placed at that coordinate location.

With reference toFIG.24, in some embodiments the initial location2408of the focus2402within the target volume of ocular tissue2404is at or near an anatomical anchor. In cases where the initial location of the focus2402is at an anatomical anchor, the derived initial coordinate set2306ofFIG.23corresponds to the location coordinates of the anatomical anchor. With reference toFIG.25, in some embodiments, the anatomical anchor may be the scleral spur14, which is also the location of the base of the trabecular meshwork12as identified in histology, and morphologically corresponds to the transition point between transparent cornea3and denser, optically thick sclera2.

With reference toFIGS.23and24, the relevant patient data2308used to derive the coordinate set2306for an initial location2408corresponding to anatomical anchor14includes the patient's set of natural anatomical measurements, e.g., CCT2301, W2W2303, and Ra2305, corresponding to the corneal meridian with which the laser beam201of the integrated surgical system1000is aligned, and the patient's demographic data, e.g., age2307. The relevant optics data2309used to derive the coordinate set2306for an initial location2408includes the radius of curvature RC2315of a concave surface of an optical component, and a thickness t2317of the optical component that is or will be coupled to the patient's eye during treatment.

Regarding the patient's set of natural anatomical measurements, consideringFIG.21, if the laser beam201is aligned along the nasal-temporal meridian2124for delivery in the 3 o'clock direction (or the 9 o'clock direction), the patient's relevant set of natural measurements CCT2301, W2W2303, and Ra2305include: the central corneal thickness (CCT)2102, the nasal-temporal W2W (W2Wnt)2104, and the nasal-temporal anterior cornea radius of curvature (Rant)2112. If, however, the laser beam201is aligned along the superior-inferior meridian2126for delivery in the 6 o'clock direction (or the 12 o'clock direction), the patient's relevant set of natural measurements CCT2301, W2W2303, and Ra2305include: the central corneal thickness (CCT)2102, the superior-inferior W2W (W2Wsi)2106, and the superior-inferior anterior cornea radius of curvature (Rasi)2114. Again, the relevant patient data2308used to derive the coordinate set2306may be for any corneal meridian.

Regarding the optics data2309, e.g., the radius of curvature RC2315and thickness t2317of optical component, with reference toFIGS.9a, and25, during a laser treatment procedure an optical component in the form of a window801of a patient interface800is docked between the cornea3and an exit lens710of a focusing objective head700(seeFIG.9a) of the integrated surgical system1000. As shown inFIG.25, a concave surface812of the window801of the patient interface contacts the anterior surface2502of the cornea3, and a convex surface813contacts a surface711of the exit lens710of the focusing objective head. This applanation of the window801to the eye deforms the anterior surface2502of the cornea3, which in turn deforms the posterior surface2504of the cornea. As described later below, the anatomical anchor locator2304accounts for deformation of the anterior surface2502and the posterior surface2504of the cornea3due to applanation during a treatment procedure based on the optics data2309, e.g., the radius of curvature RC2315of the concave surface of the window801.

Having the relevant patient data2308for the relevant meridian of the eye and the optics data2309(collectively referred to herein as treatment data), the anatomical anchor locator2304derives a coordinate set2306for an initial location2408corresponding to an anatomical anchor14of the patient. To this end, and with reference toFIG.25:

1) The anatomical anchor locator2714generates a natural anterior curve based on patient data2308, including the W2W, k, and the natural anterior radius of curvature Ra. This is done using the following equation:

y⁡(θ)=-c⁢ρ21+1-(1+k)⁢c2⁢ρ2+C⁢C⁢T+t(Eq.3)where:θ is the rotational angle corresponding to the relevant meridian of the eye;y is sag, the distance from an origin2512along the y axis, where the origin is at the apex of the window801;c is the curvature (the inverse of the natural anterior radius of curvature Ra2305);k is the natural conic constant (derived from the patient's age2307using Eq. 2);ρ is the radius, the distance from the origin2512along the ρ axis;CCT is the central corneal thickness2301; and is constant; andt is the thickness of the window801; and is constant.

Note that the rotational angle θ may be the position of the turret about the y axis705or “sweep angle” (as shown inFIGS.24and25) and is defined for θ=0 at the superior position (12 o'clock) for either the left or the right eye and to be positive clockwise when looking from the top of the eye. For example, with reference toFIG.21, θ=90 for the left eye is nasal, θ=180 is inferior and θ=270 is temporal. For the right eye (not shown inFIG.21), θ=90 is temporal, θ=180 is inferior and θ=270 is nasal.

Note that in Eq. 1 (and all other equations for y herein) y(θ) has a negative sign because the origin2512(seeFIG.25) of the cylindrical coordinate system is above the anterior surface2502of the cornea3and the cornea bends downward, toward the iris9.

Because each of t and CCT is a constant for a particular patient, the last two terms in Eq. 3 represent a fixed offset which is the distance from the origin2512to the apex2514of the posterior surface2504of the cornea3.

The natural c (the inverse of the natural anterior radius of curvature Ra2305) and the natural conic constant k are substituted in Eq. 3, and a number of different radius positions from the origin out to one-half the natural W2W2303are individually substituted for ρ to obtain a corresponding number of values of y. In one example, the number of radius positions is 500. The values of y as a function of ρ define a curve corresponding to the natural anterior curve. While the natural anterior curve is not shown inFIG.25due to applanation of the window801to the cornea3, the natural anterior curve would be the curve of the anterior surface2502of the cornea if the window was not coupled to the cornea.

2) The anatomical anchor locator2714then generates a natural posterior curve based on the patient data2308, including the W2W, k, CCT, and the natural anterior radius of curvature Ra. This is done using the following equation:

y⁡(θ)=-c⁢ρ21+1-(1+k)⁢c2⁢ρ2+C⁢C⁢T+t(Eq.4)where:θ is the rotational angle corresponding to the relevant meridian of the eye;y is sag, the distance from the origin2512along the y axis;c is the curvature (the inverse of the natural posterior radius of curvature Rp, where Rp=Ra/1.22);k is the natural conic constant (derived from the patient's age2307using Eq. 2);ρ is the radius, the distance from the origin2512along the ρ axis; andCCT is the central corneal thickness2301; andt is the thickness of the window801.

The natural c (the inverse of the natural posterior radius of curvature Rp), the natural conic constant k, and the natural CCT are substituted in Eq. 4, and a number of different radius positions from the origin out to one-half the natural W2W2303are individually substituted for ρ to obtain a corresponding number of values of y. The values of r substituted into the equation may corresponds to the same values of ρ substituted in Eq. 3 when generating the natural anterior curve. In one example, the number of radius positions is 500. The values of y as a function of ρ define a curve corresponding to the natural posterior curve. While the natural posterior curve is not shown inFIG.25due to applanation of the window801to the cornea3, the natural posterior curve would be the curve of the posterior surface2504of the cornea if the window was not coupled to the cornea.

3) The anatomical anchor locator2304then generates a deformed anterior curve based on the patient data2308, including the conic constant k and the W2W, and optics data2309, including the radius of curvature of the window801coupled to the anterior surface2502of the cornea3. This is done using the following equation:

y⁡(θ)=-c⁢ρ21+1-(1+k)⁢c2⁢ρ2+C⁢C⁢T+t(Eq.5)where:θ is the rotational angle corresponding to the relevant meridian of the eye;y is sag, the distance from the origin2512along the y axis;c is the curvature (the inverse of the radius of curvature2315of the window801);k is the natural conic constant (derived from the patient's age using Eq. 2); andρ is the radius, the distance from the origin2512along the ρ axis;CCT is the central corneal thickness2301; andt is the thickness of the window801.

The value of c (the inverse of the radius of curvature of the window801), and the natural conic constant k are substituted in Eq. 5, and a number of different radius positions from the origin out to one-half the natural W2W2303are individually substituted for ρ to obtain a corresponding number of values of y. The values of ρ substituted into the equation may corresponds to the same values of ρ substituted in Eq. 3 when generating the natural anterior curve. In one example, the number of radius positions is 500. The values of y as a function of r define a curve corresponding to the deformed anterior curve2502.

4) The anatomical anchor locator2304then calculates the arc length of the deformed anterior curve2502and the arc length of the deformed posterior curve2504using known equations, wherein the arc length corresponds to the distance along the respective curve between the minimum radius (origin) and the maximum radius (W2W/2).

5) The anatomical anchor locator2304then determines a deformed posterior curve using the boundary conditions that the posterior corneal arc length is constant (does not change after deformation). In other words, the natural posterior arc length is equal to the deformed posterior art length. With reference toFIG.25, arc length refers to the distance between two points on a curve. Thus, a full corneal arc length of a corneal cross-section (as shown inFIG.25) is the distance along the arc from one end of the cornea3to the other end. While a half corneal arc length refers to the distance along the arc from one end of the cornea3to the point on the curve at the azimuthal axis705.

Continuing with reference toFIGS.23and25, the deformation module2318of the anatomical anchor locator2304calculates a corresponding posterior surface point2510for each of a discrete number of anterior surface points2506along the deformed anterior surface2502arc length. Based on the previously derived natural anterior curve and natural posterior curve, the deformation module2318determines a normal thickness (tc) of the cornea3at various points along the length of the natural cornea. Because the thickness of the cornea3is not impacted by applanation of the window801, the deformation module2318applies these known normal thicknesses to determine a corresponding posterior surface point2510for each of a number of anterior surface points. Each corresponding posterior surface point2510is in a direction normal to an anterior tangent2508through its corresponding anterior surface point2506and is a distance equal to the normal thickness (tc) at that point from the corresponding anterior surface point2506. The number of discrete anterior surface points2506may correspond to the number of radius positions used to generate the deformed anterior curve. The number of discrete posterior surface points2510define a deformed posterior curve2504.

6) The deformation module2318of the anatomical anchor locator2304then fits a deformed posterior fitted curve (not shown inFIG.25) to the deformed posterior curve2504by fitting to the following equation using non-linear least squares to numerically calculate a deformed posterior conic constant k and deformed posterior base radius of curvature Rp:

y⁡(θ)=-c⁢ρ21+1-(1+k)⁢c2⁢ρ2+C⁢C⁢T+t(Eq.6)where:θ is the rotational angle corresponding to the relevant meridian of the eye;y is sag (as shown inFIG.25), the distance from the origin2512along the y axis;c is the curvature (the inverse of the deformed posterior base radius of curvature);k is the deformed conic constant; andρ is the radius, the distance from the origin2512along the ρ axis;CCT is the central corneal thickness2301; andt is the thickness of the window801.

In the fitting process, various values for c and k are arbitrarily selected and values of y are determined, until the values for y from the origin along the ρ axis define a deformed posterior fitted curve that closely fits to the deformed posterior curve2504. The values for c and k that produce the deformed posterior fitted curve define the deformed posterior base radius of curvature Rp2311and the deformed conic constant k2313for the patient.

Having now determined a deformed posterior base radius of curvature Rp2311and a deformed conic constant k2313for the patient being treated, based on the relevant patient data2308and optics data2309, the initial coordinate set2306may be determined based on a coordinate system. For example, using a cylindrical coordinate system with the origin2512defined at the apex of the window801of the patient interface—a fixed location associated with optics of the surgical system that is invariant of patient anatomy—then the cylindrical coordinates (ρ, θ, y(θ)) of the location of the scleral spur14of the eye coupled to the window801, and hence the initial location2408of the focus2402ofFIG.24is obtained by inserting values for ρ, Rp, k, CCT, and t in the following equation to solve for y(θ):

y⁡(θ)=-c⁢ρ21+1-(1+k)⁢c2⁢ρ2+C⁢C⁢T+t(Eq.7)where:θ is the rotational angle corresponding to the relevant meridian of the eye;y is the distance from the origin2512along the azimuthal axis705;ρ is the radial distance from the origin2512along the ρ axis and is set equal to one-half of W2W;c is the inverse of Rp, which is the deformed posterior base radius of curvature2311;k is the deformed conic constant2313; W2W is the white-to-white diameter2303along the relevant meridian of the eye;CCT is the central corneal thickness2301; andt is the thickness of the window801.

The first term in Eq. 7 represents the azimuthal distance, or “sag”, of a conic posterior corneal surface as a function of the radial coordinate, ρ, and sweep angle, θ. As noted above, in the first term in Eq. 7, Rp is the base posterior radius of curvature and k is the deformed conic constant, each of which are calculated by the deformation module2318ofFIG.23. As the eye is non-rotationally symmetric, then Rp is a function of θ. For example, from the above definitions, if θ=90 (nasal for left eye and temporal for the right eye) then Rp=Rpntas this would correspond to the nasal-temporal axis. Alternatively, if θ=180 (inferior location for both eyes) then Rp=Rpsi. With reference toFIG.25, the radial coordinate, ρ, is 0 along the azimuthal axis705(through the center of the eye) and reaches its maximum value at the scleral spur14location, or half the white-to-white diameter (W2W).

Further regarding the base posterior radius of curvature Rp, the surface profile or “sag” of a conical section is mathematically described in Eq. 7, which has a radius of curvature Rp and a conic constant k. If the conical section was purely spherical then k=0 and the base radius of curvature=true radius of curvature. The base radius of curvature Rp is essentially the radius of curvature obtained when a spherical surface fit is applied to the conical surface. However, since the corneal surface is not purely spherical then the true surface deviates from this fitted spherical surface. The deformed conic constant k provides an additional descriptive variable and allows recovery of the true surface.

Returning to block2202ofFIG.22, and with additional reference toFIGS.23and24, having determined the cylindrical coordinates (ρ, θ, y(θ)) corresponding to the initial coordinate set2306, the laser focus2402is placed at an initial location2408in the volume of ocular tissue2404. To this end, the treatment plan module2310is configured to output a control signal2320to control beam conditioners, scanners500of the integrated surgical system1000that causes the beam conditioners, scanners to position the focus2402based on the initial coordinate set2306.

It is noted that the initial coordinate set2306is defined by a local coordinate system associated with the energy control module2302. Within the local coordinate system, the initial coordinate set2306may be determined based on one coordinate system while the coordinate entries in the LUT2314are based on a different coordinate system. For example, in the above description, the initial coordinate set2306determined by the anatomical anchor locator2304is based on a cylindrical coordinate system, and the coordinate entries in the LUT2314are based on a Cartesian coordinate system. To account for this, the treatment plan module2310may be configured to transform the initial coordinate set2306received from the anatomical anchor locator2304to a coordinate system that matches the LUT of the energy control module2302.

At block2204ofFIG.22, and with additional reference toFIGS.23and24, having placed the focus2402at the initial location2408, photodisruptive energy is applied by the laser201at the initial location in accordance with an energy parameter that is based on the initial location2306of the focus within the target volume of ocular tissue2404. To this end, the energy control module2302is configured to output an energy control signal2322to the FS laser source200that informs the laser source of the initial energy parameter to be used when applying photodisruptive energy at the initial location2408. In some embodiments, the energy control module2302includes a database or look up table (LUT)2314that maps coordinate locations to one or more energy parameters. The energy control module2302is configured to locate the LUT entry that matches the initial coordinate set2306and to locate the energy parameter mapped to that entry. The energy parameter found in the look up table corresponds to an energy level (p J) sufficient to disrupt the tissue at the location of the focus2402. In other words, the energy level (p J) is sufficient to disrupt the tissue within a volume corresponding in size to the focus spot size2406at the location of the focus2402.

At block2206ofFIG.22, and with additional reference toFIGS.23and24, the focus2402of the laser201is moved to a subsequent location within the target volume of ocular tissue2404. To this end, a subsequent coordinate set2312corresponding to the subsequent location of the focus2402within the target volume of ocular tissue2404may be derived based on the initial coordinate set2306. For example, with reference toFIG.20, the subsequent coordinate set2312may be a spot separation2002away from the initial coordinate set2306in one or both of the x or y direction. The subsequent coordinate set2312may be defined by a treatment pattern programmed into the treatment plan module2310, and movement of the laser201to the subsequent location is enabled by control signals2320configured to control beam conditioners, scanners500of the integrated surgical system1000to position the laser focus2402based on the subsequent coordinate set2312.

It is noted that the scanning of the laser during treatment may be based on a local coordinate system relative to the treatment pattern P1through which the laser is being scanned. For example, with reference toFIGS.19and20, the treatment pattern P1may be defined by a Cartesian coordinate system relative to the scanner of the integrated surgical system1000. In some cases the origin of the local coordinate system of the energy control module2302may be different from the origin of the local coordinate system of the scanner of the integrated surgical system1000. In such cases, when deriving the subsequent coordinate set2312based on the initial coordinate set2306, the treatment plan module2310may perform origin and/or coordinate translations in order to express the subsequent coordinate set2312in terms of the coordinate system of LUT2314.

At block2208ofFIG.22, and with additional reference toFIGS.23and24, after the focus2402is moved to the subsequent location corresponding to the subsequent coordinate set2312, photodisruptive energy is applied by the laser201at the subsequent location in accordance with an energy parameter that is based on the subsequent location of the focus within the target volume of ocular tissue2404. The energy parameter for the subsequent coordinate set2312may be determined from the look up table2314of the energy control module2302.

In some embodiments the energy parameter is determined on a location-by-location basis. In other words, for each different coordinate set2306,2312included in a treatment pattern, the look up table of the energy control module2302is used to determine the energy parameter for that location and provide dynamic adjustment of the energy of the laser as the focus2402is scanned through the treatment pattern within the target volume of ocular tissue2404. With reference toFIGS.19and20, Table 4 is an example look up table2314that provides a corresponding energy level for spot1904locations in an XY scan plane1902at a fixed depth z1 of a treatment pattern. As described below in the Look Up Table Generation section of this disclosure, the energy level assigned to a coordinate (x,y,z) is based on an estimated laser spot size at that coordinate location. Accordingly, for purposes of explanation estimated spot size information is included in the example lookup table2314shown in Table 4. The actual look up table2314resident in the control system100may or may not include this estimated spot size information. In Table 4 the number after x corresponds to the column position (e.g., 1-8, from left to right inFIG.20), the number after y corresponds to row position (e.g., 1-5, from bottom to top inFIG.20), and the number after z corresponds to the depth or layer position (e.g., 1-6, from front to back inFIG.19).

In some embodiments the energy parameter corresponds to a measure of photodisruptive energy across a plurality of different locations of the focus2402. For example, the measure of photodisruptive energy may correspond to a minimum energy level that ensures photodisruption at each of a plurality of different locations of the focus2402within the volume of ocular tissue2404. In other words, the energy level delivered while treating a particular volume of ocular tissue2404is kept constant and at a level that assures photodisruption occurs at each location2408, as specified by the coordinate sets2306,2312included in a treatment pattern, through which the focus4202is scanned.

In some embodiments the energy parameter is based on the estimated spot size2406of the laser focus2402at each location2408, as specified by the coordinate sets2306,2312through which the focus4202is scanned, and is an energy level that maintains a constant fluence. For example, Table 5 shows laser energy as a function of estimated spot size2406to maintain a constant 1 J/cm2fluence.

A larger fluence level can be selected to assure photodisruption always occurs i.e., Table 5 could be re-computed using 1.5 J/cm2.

Returning toFIG.22, and with additional reference toFIGS.23and24, at block2210, if the focus2402of the laser201has scanned through the target volume of ocular tissue2404the process proceeds to block2212where the laser treatment of the volume of ocular tissue ends. If the focus2402of the laser201has not scanned through the target volume of ocular tissue2404the process repeatedly cycles through blocks2206and2208until the focus of the laser has scanned through the target volume of ocular tissue. For example, with reference toFIGS.19and24, the focus2402may be scanned in multiple directions relative to the target volume of ocular tissue2404through an XY treatment plane1902, and then moved in the z direction and scanned through another XY treatment plane, to thereby photodisrupt one or more layers of tissue of the target volume of ocular tissue. This is repeated until the focus2402has scanned through the entirety of the treatment pattern P1and thus through the target volume of ocular tissue2404.

At block2212ofFIG.22, and with additional reference toFIGS.23and24, if treatment of the volume of ocular tissue2404is complete, the entire method ofFIG.22may then be repeated for one or more different alignments of the laser beam to treat different target volumes of ocular tissue. To this end, the turret of the surgical system1000may be rotated to align the laser beam201along a different meridian of the cornea for delivery in a different clock time direction. With reference toFIG.21, in some embodiments the turret is configured to rotate in 3° increments, and there are ten increments2130between adjacent clock hours. For example, the turret may be rotated five increments to align the laser beam201along a subsequent meridian2128. In this case, the patient's central corneal thickness (CCT)2102, W2W diameter along the subsequent meridian2128, and posterior cornea radius of curvature Rp along the subsequent meridian, which is derived from the patient's anterior cornea radius of curvature Ra along the same meridian, are the relevant patient data2308that is used at block2202ofFIG.22to determine the initial coordinate set2306ofFIG.23for the location of the anatomical anchor within the target volume of ocular tissue2404that is aligned with the different clock time direction. Note that the optics data2309, which is fixed by the optical component, is the same regardless of the meridian. This process may be repeated numerous times to treat a number of different volumes of ocular tissue around the circumference of irido-corneal angle.

Having thus described a method of laser treatment based on a patient's biometric data and a look up table that maps laser focus locations to energy parameters, a description of a method and system for generating such a look up table follows.

Look Up Table Generation

With reference toFIG.25, in accordance with embodiments disclosed herein a look up table is derived based on a clinical model that recognizes that, for a particular angle θ (i.e., the rotational angle position of the turret about the y axis705or “sweep angle”), each patient in a patient population has a unique location of an anatomical anchor, which location is determined by the patient's anatomy. In the example clinical model disclosed herein, the scleral spur is the anatomical anchor14as it serves as a clinically identifiable landmark, via either a gonioscope or OCT imaging. Furthermore, the scleral spur is associated with the trabecular meshwork12in the irido-corneal angle13, which encompass the volumes of ocular tissue that are targeted for laser treatment in accordance with the treatment methods described herein.

The clinical model also recognizes that during treatment the optical pathway to a location of an anatomical anchor may be affected by optics of the system. For example, optical variables and mechanical variables of optics, e.g., lenses, windows, etc., can lead to optical aberrations. The clinical model disclosed herein accounts for these aberrations.

The clinical model also recognizes that each patient-unique location of the anatomical anchor14may be expressed relative to a patient-invariant location2516. In the example clinical model disclosed herein, the anterior corneal apex is the patient-invariant location2516. Regarding the patient-invariant location and with reference toFIG.25, during a laser treatment procedure a concave surface812of a window801of the patient interface contacts the anterior surface2502of the cornea3, and a convex surface813contacts a surface711of an exit lens710of the focusing objective head. The window801of the patient interface800is a fixed optic of the integrated surgical system1000and provides a fixed optic location, e.g., the apex2512of the window801, determined by very tight mechanical tolerances. Therefore, the choice of the anterior cornea apex2516as a fixed, patient-invariant location is appropriate since the position of the anterior cornea apex relative to a fixed laser beam is very tightly controlled by the fixed window801.

Still referring toFIG.25, the clinical model further recognizes that, due to docking of the window801of the patient interface to the anterior surface2502of the cornea during a laser treatment procedure, the posterior surface and the anterior surface of the cornea respectively deform into a deformed posterior surface2504, and a deformed anterior surface. Because the scleral spur, i.e., the anatomical anchor14, is where the posterior surface2504of the cornea3ends, it follows that the scleral spur location also changes due to the docking of the window801to the anterior surface2502. The clinical model disclosed herein accounts for this deformation.

FIG.26is a flowchart of a method of generating a look-up table for use by a surgical system to determine an energy parameter for photodisrupting ocular tissue with a laser. The look up table maps or assigns one or more energy parameters to a number of coordinate sets. Each of these coordinate sets represents a location within a target volume of the ocular tissue at which a focus of the laser may be placed during treatment by the surgical system. After being generated, the look up table may be used as the look up table2314in the energy control module2302of the control system100inFIG.23.

The method ofFIG.26, which is described in detail below, may be implemented by a look up table generator2702shown inFIG.27. In some embodiments, the look up table generator2702includes a clinical model simulator2710, an optics model simulator2720, an anatomical anchor locator2714, and a ray tracing module2730that operate together to generate an individual spot size distribution2722for each of a plurality of different sets of simulated patient data2712and simulated optics data2713. Each individual spot size distribution2722may be defined by a collection of coordinate sets2706and a laser spot size2732for each coordinate set in the collection.

With reference toFIGS.27and28, each coordinate set2706of an individual spot size distribution2722describes a location2808relative to an origin2816. As described previously, the origin2816may correspond to the apex2512of a fixed optical component, e.g., window801(seeFIG.25). The location2808is within a modeled target volume of ocular tissue2804. Accordingly, a laser focus2802positioned at the location2808is within the modeled target volume of ocular tissue2804. The laser spot size2732associated with a coordinate set corresponds to an expected or estimated spot size2806for the laser focus2802at that location2808. As previously noted, in a clinical setting the spot size of a laser focus may vary as a function of the location of the focus within a clinical target volume of ocular tissue. The expected or estimated spot sizes2732included in the individual spot size distributions2722account for this variation.

Continuing withFIG.27, once a sufficient number of individual spot size distributions2722are created, a spot size distribution aggregator2724combines or aggregates the individual spot size distributions into a final spot size distribution2726that is defined by a collection of coordinate sets2706and a laser spot size2732for each coordinate set in the collection. Based on the final spot size distribution2726and energy parameter information, a mapping module2728produces a look up table2704that maps each of the coordinate sets2706to one or more energy parameters2708.

Having thus described the general functions of the various modules of the look up table generator2702, a detailed description of the method ofFIG.26follows.

With reference toFIG.26and additional reference toFIGS.27and28, at block2602, a plurality of individual spot size distributions2722are determined for a modeled target volume of ocular tissue2804. The modeled target volume of ocular tissue2804may correspond to, for example, a small portion, e.g., between 10 μm and 2000 μm, of tissue along or around the circumferential angle of the eye. Each of the plurality of individual spot size distributions2722is based on a different set of simulated patient data2712and includes an expected or estimated spot size2732of a laser focus2802at each of a plurality of locations2808within the modeled target volume of ocular tissue2804. The individual spot size distributions2722may be further based on different sets of simulated optics data2713.

The different sets of simulated patient data2712include anatomical measurements of the eye. These simulated anatomical measurements may include one or more of a central corneal thickness (CCT)2701, a white-to-white (W2W) diameter2703, and an anterior cornea radius of curvature Ra2705. The different sets of simulated patient data2712also include an age-based conic constant k2707.

The clinical model simulator2710is configured to generate a large number of different sets of simulated patient data2712. In one configuration, each set of simulated patient data2712includes a simulated measure of CCT, W2W, and Ra. The simulated age-based conic constant k2116is based on Eq. 2 and the clinical model simulator2710may generate these conic constants by first generating a range of simulated ages and then deriving, for each simulated age, a simulated conic constant k2707. Each set of stimulated patient data2712may be automatically generated using know simulation algorithms.

The optical model simulator2720is configured to generate a large number of different sets of simulated optics data2713. The different sets of simulated optics data2713include parameters of optical components of a surgical system that couple to the eye during a treatment procedure. These simulated optics data2713may include, for example, one or more of a thickness t2715of a window801or a radius of curvature RC2717of the concave surface of the window. Each set of stimulated optics data2713may be automatically generated using know simulation algorithms.

The simulated optics data2713provided by the optics model stimulator2720is included in the modeling process to account for optical aberrations of one or more of the simulated optics of a laser surgical system, and an anatomy of the simulated patient, while simulating a propagation path of a laser beam. Optical aberrations of optics, e.g., the exit lens710of the focusing objective head, the window801of the patient interface, to be used during a procedure determine the spot size throughout the volume of ocular tissue. For a complex optical design, there are many optical variables and mechanical variables which can lead to optical aberrations. Optical tolerances may include but are not limited to surface radius of curvature, irregularity, glass thickness, Abbe number, and index of refraction, the flatness of reflective surfaces and the wedge of each lens (runout). Mechanical tolerances may include but are not limited to tilt and decenter of individual components such as lenses, mirrors and dichroics and tilt/decenter for sub-assemblies and assemblies. A ray tracing module2730of the look up table generator2702, which is described later below further accounts for these optical aberrations as part of the simulation and ray tracing process.

A simulated patient's anatomy may also contribute to optical aberrations. For example, the steeper a patient's posterior surface of a cornea, the more the light bends and the more aberrations are produced. Or the smaller the eye, the higher up (closer to the global datum) the trabecular meshwork12is, which leads to more aberrations. More aberrations result in a larger spot size. As previously mentioned, a certain fluence is required to cause photodisruption and “cut” human tissue. This fluence is approximately 1 J/cm2. Accordingly, if the spot size of a laser focus is larger due to optical aberrations, then to ensure the same fluence, the energy should be increased. The ray tracing module2730also accounts for these optical aberrations as part of the simulation and ray tracing process.

The focusing objective head of a surgical system, mounted on a motorized translation stage, moves to function as a “compensator” and ensures a tightly focused, near or fully diffraction-limited spot size at different depth planes. The optical design has been optimized through a large depth range, such that as the objective moves, the focus moves with it. The overall outcome is not a constant spot size with depth, but instead the spot size change is minimized through depth. As the laser focus targets different x, y and z locations, the amount and type of optical aberrations change. So incorporating a moving group of lenses provides an additional design “degree of freedom” to minimize these depth-dependent aberrations. Accordingly, movement of the objective to account for variations in the location of the trabecular meshwork12of the simulated patients is also accounted for by the ray tracing module2730in the simulation and ray tracing process (described later below).

In one example process of generating a look up table2704, the clinical model simulator2710simulated 2500 patients by generating2500unique, different sets of simulated patient data2712for one modeled target volume of ocular tissue2804of the circumference of the eye using Monte Carlo distributions. As previously mentioned, the modeled target volume of ocular tissue2804may correspond to, for example, a small portion, e.g., between 10 μm and 2000 μm, of tissue along or around the circumferential angle of the eye. For the CCT2701distribution, a literature review was conducted to find published clinical study data. In each study, a mean and standard deviation value of CCT2701was reported. The results from the studies were combined to calculate an aggregate, mixture average and standard deviation for CCT2701, which were used for Monte Carlo distribution purposes. This process was repeated for the distributions of the white-to-white diameters W2W2703, and the natural anterior radii of curvature Ra2705. The optical model simulator2720generated2500unique, different sets of simulated optics data2713using Monte Carlo distributions.

Having generated different sets of simulated patient data2712and simulated optics data2713(collectively referred to herein as simulated data) the anatomical anchor locator2714determines a location of the anatomical anchor14for each set of simulated data. To this end, and with reference toFIGS.29a-1through29a-3, for each set of simulated data:

1) The anatomical anchor locator2714generates a natural anterior curve based on simulated patient data2712, including the W2W, k (which may be derived using Eq. 2 and based on simulated age), and the anterior radius of curvature Ra. This is done using the following equation:

y=c⁢r21+1-(1+k)⁢c2⁢r2+C⁢C⁢T+t(Eq.9)where:y is sag, the distance from the origin along the Sag (mm) axis (note that the origins in the graphs ofFIGS.29a-1through29a-3are not shown and are at “0”, above −1;c is the curvature (the inverse of the simulated base anterior radius of curvature Ra2705);k is the simulated conic constant2707;r is the radius, the distance from the origin along the Radius (mm) axis;CCT is the central corneal thickness2701; andt is the simulated thickness of the optical component, e.g., window801.

The simulated c (the inverse of the simulated base anterior radius of curvature Ra) and the simulated conic constant k are substituted in Eq. 9, and a number of different radius positions from the origin out to one-half of the simulated W2W2703are individually substituted for r to obtain a corresponding number of values of y. In one example, the number of radius positions is 500. The values of y as a function of r define a curve corresponding to the natural anterior curve. Examples of natural anterior curves are illustrated inFIGS.29a-1through29a-3.

2) The anatomical anchor locator2714then generates a natural posterior curve based on simulated patient data2712, including the W2W, k, CCT, and the anterior radius of curvature Ra. This is done using the following equation:

y=c⁢r21+1-(1+k)⁢c2⁢r2+C⁢C⁢T+t(Eq.10)where:y is sag, the distance from the origin along the Sag (mm) axis;c is the curvature (the inverse of the simulated base posterior radius of curvature Rp, where Rp=Ra/1.22);k is the simulated conic constant2707;r is the radius, the distance from the origin along the Radius (mm) axis; andCCT is the simulated central corneal thickness2701; andt is the simulated thickness of the optical component, e.g., window801.

The simulated c (the inverse of the simulated base posterior radius of curvature Rp), the simulated conic constant k, and the simulated CCT are substituted in Eq. 10, and a number of different radius positions from the origin out to the simulated W2W are individually substituted for r to obtain a corresponding number of values of y. The values of r substituted into the equation may corresponds to the same values of r substituted in Eq. 9 when generating the natural anterior curve. In one example, the number of radius positions is 500. The values of y as a function of r define a curve corresponding to the natural posterior curve. Examples of natural posterior curves are illustrated inFIGS.29a-1through29a-3.

3) The anatomical anchor locator2714then generates a deformed anterior curve based on simulated patient data2712, including the simulated k, and simulated optics data2713, including the radius of curvature of a window801coupled to the anterior surface of the cornea of the simulated patient. This is done using the following equation:

y=c⁢r21+1-(1+k)⁢c2⁢r2+C⁢C⁢T+t(Eq.11)where:y is sag, the distance from the origin along the Sag (mm) axis;c is the curvature (the inverse of the simulated radius of curvature2717of the optical component);k is the simulated conic constant2707; andr is the radius, the distance from the origin along the Radius (mm) axis.CCT is the central corneal thickness2701; andt is the simulated thickness of the optical component, e.g., window801.

The simulated c (the inverse of the simulated radius of curvature of the optical component), and the simulated conic constant k are substituted in Eq. 11, and a number of different radius positions from the origin out to one-half of the simulated W2W2703are individually substituted for r to obtain a corresponding number of values of y. The values of r substituted into the equation may corresponds to the same values of r substituted in Eq. 9 when generating the natural anterior curve. In one example, the number of radius positions is 500. The values of y as a function of r define a curve corresponding to the deformed anterior curve. Examples of natural posterior curves are illustrated inFIGS.29a-1through29a-3.

4) The anatomical anchor locator2714then calculates the arc length of the natural anterior curve and the arc length of the natural posterior curve using known equations, wherein the arc length corresponds to the distance along the respective curve between the minimum radius (origin) and the maximum radius (W2W/2).

5) The anatomical anchor locator2714then determines a deformed posterior curve using the boundary conditions that the posterior corneal arc length is constant (does not change after deformation). In other words, the natural posterior arc length is equal to the deformed posterior arc length. With reference toFIGS.29a-1through29a-3, half corneal arc lengths are shown, each corresponding to the distance along the arc from one end of the cornea3to point on the curve at the Sag axis.

With reference toFIG.25, the deformation module2718of the anatomical anchor locator2714calculates a corresponding posterior surface point2510for each of a discrete number of anterior surface points2506along the deformed anterior surface2502arc length. Based on the previously derived natural anterior curve and posterior curves, the deformation module2718determines a normal thickness (tc) of the cornea3at various points along the length of the natural cornea. Because the thickness of the cornea3is not impacted by applanation of the window801, the deformation module2718applies these known normal thicknesses to determine a corresponding posterior surface point2510for each of a number of anterior surface points. Each corresponding posterior surface point2510is in a direction normal to an anterior tangent2508through its corresponding anterior surface point2506and is a distance equal to the normal thickness (tc) at that point from the corresponding anterior surface point2506. The number of discrete anterior surface points2506may correspond to the number of radius positions used to generate the deformed anterior curve. The result is the deformed posterior curve. Examples of deformed posterior curves are illustrated inFIGS.29a-1through29a-3.

6) The anatomical anchor locator2714then fits a deformed posterior fitted curve to the following equation using non-linear least squares to numerically calculate a deformed posterior conic constant k and deformed posterior base radius of curvature Rp:

y=c⁢r21+1-(1+k)⁢c2⁢r2+C⁢C⁢T+t(Eq.12)where:y is sag, the distance from the origin along the Sag (mm) axis;c is the curvature (the inverse of the deformed base radius of curvature);k is the deformed conic constant;r is the radius, the distance from the origin along the Radius (mm) axis;CCT is the central corneal thickness2701; andt is the simulated thickness of the optical component, e.g., window801.

In the fitting process, various values for c and k are arbitrarily selected and values of y are determined, until the values for y from the origin along the Radius (mm) axis define a deformed posterior fitted curve that closely fits to the deformed posterior curve. The values for c and k that produce the deformed posterior fitted curve define the deformed posterior base radius of curvature Rp2711and a deformed conic constant k2719for the simulated patient.

Regarding the various simulated patients shown inFIGS.29a-1through29a-3, differences in simulation cases are noted. For example, consider EID12. Here the simulated patient's natural anterior curve is flatter than the patient's deformed curve due to applanation of the patient interface (e.g., window801). When docking occurs the simulated patient's cornea is forced to the steeper patient interface shape. This causes the posterior surface to also “bend” down, as shown by the deformed posterior curve relative to the natural posterior curve. Therefore, for this simulated patient, the anatomical anchor location (which is at the end of the posterior fitted curve) is deeper into the trabecular meshwork (larger, more negative sag value) after deformation than in its natural state. Thus, the sag value corresponding to the end of the posterior fitted curve is greater (e.g., more negative) than the sag value corresponding to the end of the natural posterior curve. For the simulated patient of EID9, the opposite is true and instead the anatomical anchor location (which is at the end of the posterior fitted curve) is shallower than its natural position. Thus, the sag value corresponding to the end of the posterior fitted curve is less (e.g., less negative) than the sag value corresponding to the end of the natural posterior curve.

Having now determined a deformed posterior base radius of curvature Rp2711and a deformed conic constant k2719for the simulated patient based on the simulated patient data2712and the simulated optics data2713, the coordinate set2716of the location of an anatomical anchor14may be determined based on a coordinate system. For example, using a cylindrical coordinate system with the origin2816defined at the apex of the window801of the patient interface—a fixed location associated with optics of the surgical system that is invariant of patient anatomy—then the coordinates (ρ, θ, y) of the location2808of the scleral spur14of the simulated patient is obtained by inserting values for p, Rp, k, CCT, and t in the following equation to solve for y:

y=-c⁢ρ21+1-(1+k)⁢c2⁢ρ2+C⁢C⁢T+t(Eq.13)where:y is the distance from the origin2816along the y axis2814;ρ is the radial distance from the origin2816along the ρ axis2818and is set equal to one-half of W2W;c is the inverse of Rp, where Rp is the deformed posterior base radius of curvature2711of the simulated patient;k is the deformed conic constant2719;W2W is the white-to-white diameter2703;CCT is the central corneal thickness2701; andt is the simulated thickness of the optical component, e.g., window801.

With reference toFIG.29b, and continuing with the 2500 anatomical model simulation described above, the deformed posterior curve2904of the cornea3of a number of simulated patient is represented by a separate curved line in a single graph. For clarity of illustration only ten curved line are shown. For each simulated patient, the location of the scleral spur14and therefore trabecular meshwork12is at the end of the curved line representing the deformed posterior surface2904. For each simulated patient, the z-axis or p-axis span is equal to half the W2W diameter. The sag (y) is determined from Eq. 13 above for y(θ). The apex of the anterior surface of the window801, is taken as the origin. Regarding Eq. 13, in the model each of t and CCT is considered to be a constant, and the last two terms in Eq. 13 represent a fixed offset which is the distance from a simulated origin2912to a simulated apex2914of the posterior surface2904of the cornea3.

Continuing further with block2602ofFIG.26, and with additional reference toFIGS.27and28, having determined the location of the anatomical anchor14for a set of simulated patient data, a ray tracing module2730determines an individual spot size distribution2722for each different set of simulated patient data. To this end, the ray tracing module2730simulates a propagation path2809of a laser beam through an anterior chamber7of an eye into the determined location of the anatomical anchor14, and calculates a spot size2806of the focus of the laser beam at the location of the anatomical anchor and at other coordinate locations2807about the anatomical anchor, through which the focus may be scanned. The optics model simulator2720may simulate the propagation path of a laser beam and calculate spot sizes using geometric ray tracing capabilities of an engineering optical physics software, such as Zemax OpticStudio.

In the example based on 2500 sets of simulated data, for each of the 2500 simulations, the optics model simulator2720ran a ray trace to calculate the femtosecond spot size at twenty-seven different locations2806,2807covering a representative channel in the trabecular meshwork sized 200 μm azimuthal×500 μm circumferential×400 μm depth. Different sized channels are possible. For example, the circumferential size may be increased to extend the spot size distribution further around the circumference of the eye. In any case, the entire volume of ocular tissue covered by the location of these 2500 channels is referred to herein as a surgical volume or surgical envelope. The representative surgical volume was anchored at the scleral spur x, y, and z location as determined by the anatomical anchor locator2714. The spot size metric was taken to be the diameter encircling focused energy values of 10% to 90%. With reference toFIG.28, these twenty-seven locations2806,2807comprised three sets of nine locations each, where each set was evaluated at a different fixed depth z location. The depth planes or slices were spaced apart evenly throughout the volume (0, 200 and 400 μm relative to the starting position). Note for clarity of illustration, only one set of nine locations2806,2807is shown inFIG.28. Also, while the spot sizes at the nine location2806,2807are shown as the same size, the actual spot sizes may vary, with some of them being larger or smaller than illustrated inFIG.28.

Further describing the ray tracing process, rays are traced through the optical system and light-matter interaction (reflection, refraction) are calculated for each ray at each surface. In each case of refraction of reflection, the equations are known and the subsequent trajectory of the ray can be calculated using these known equations. In this way, each ray trajectory is sequentially traced through the optical system.

All of these rays strike the “image,” which is the surface at the ray's terminate. In this case, the “image” is the surface of the trabecular meshwork.

These rays do not all converge on a single, infinitesimally small point and instead “spread out.” The level of spread is due to two major factors. Firstly, the laws of physics (diffraction) which govern a finite, minimum spot size. Secondly, the tolerances and variations described above (optical, mechanical and anatomical) which will cause the spot size to further expand beyond the diffraction limit. The second component are known as introducing “aberrations” and the heterogenous eye anatomy is a key component of these aberrations. For example, because of the oblique angle at which a laser may enter the eye in the integrated surgical system1000disclosed herein, astigmatism is the primary anatomy-induced aberration. To a secondary degree, another aberration known as “coma” differs across the patient population.

The spatial distribution of where these rays fall on the image, e.g., the surface of the trabecular meshwork, can be mathematically calculated in different ways to calculate a spot size. The ray tracing module2730uses the D1090 value, which is a well-established metric for measuring and calculating laser spot sizes. The spot size physically represents the area within which a defined amount of energy resides. The larger the spot size, the more spread out the energy is, and therefore the more input energy is required to achieve the photodisruption threshold for tissue. Furthermore, the shape of the spot is also important and the spot size calculation captures this also. The difference in eye anatomy will cause the ray to trace differently through the eye, will introduce different aberrations, and will affect the spot size.

Regarding the D1090 spot size calculation method, this method is equivalent to a “knife-edge width” measurement where the “width of the beam is defined as the distance between the points of the measured curve that are 10% and 90% of the maximum value. Prior to advanced software and CCD cameras, the knife edge method was the standard laboratory technique. It corresponds to measuring the total beam energy and then traversing a knife-edge so that it encroaches on the beam and subsequently reduces the power recorded on a detector. The knife blade is moved at fixed increments until the detector records zero power. A computational equivalent of this knife edge technique may be used to calculate spot size. While not a standard measurement, it is ISO recommended and one that is used by companies that make beam measurement technology. See for example, White Paper—Apples to Apples: Which Camera Technologies Work Best for Beam Profiling Applications, Part 2: Baseline Methods and Mode Effects, by G. E. Slobodzian (https://www.ophiropt.com/laser—measurement/knowledge-center/article/8065?r=blog).

Returning toFIG.26, and with additional reference toFIG.27, at block2604, the individual spot size distributions2722resulting from the number of simulations and generated by the ray tracing module2730are aggregated or combined to obtain a final spot size distribution2726. For example, the spot sizes across different individual spot size distributions2722that are in spatially overlapping locations within a simulated target volume of ocular tissue may be combined using known interpolation techniques, such as gridded interpolation. The combined spot size distribution includes a final expected or estimated spot size of the laser focus at the plurality of locations of the focus within a simulated target volume of ocular tissue.

For a single patient, as perFIG.28, there are a 9 simulated spots at three different depth planes, for a total of 27 spots per patient. Each one of these spots has a spatial co-ordinate (x, y, z). For n patients, there would then be 27n spots. Mathematically, this data could be described in a matrix (table) with 27n rows and 4 columns. Each row represents a spot with the first column as a spot size D1090 value, and the second, third and fourth columns are the corresponding x, y, and z co-ordinate value for that spot size, respectively. Rows 1-27 would be for the first patient, 28-54 for the second patient, 55-81 for the third patient, etc. until row 27n.

The total ocular surgical envelope represents a volume that is bounded by the minimum and maximum values of x, y, and z. The surgical volume can be discretized in all three dimensions with equal spacing such that it is a 3D “mesh” or a “grid”, somewhat like a crystal lattice. For example, with equal spacing of 0.01 in all three dimensions, if the minimum and maximum values of x are −1 to 1, y are −2 to 2, and z are −3 to 3, then there would be 200 grid points in x, 400 in y and 600 in z, for a total of 200×400×600 points (minus the number of corners, 8, where there is overlap between the gridded points). Grid interpolation is a numerical method of using the data (the 27n×4 matrix described above) to interpolate a spot size to each of the x, y and z locations of the grid. For example, for a particular grid location of x′, y′, and z′, the algorithm is configured to find the nearest six (x, y, z) locations in the simulated spot size matrix and estimate the spot size at (x′, y′, z′) by using mathematical interpolation. Interpolation is essentially an “estimation”—finding new data values based on measured (in case simulated) data. Six is just an example number. This gridded interpolation may be done in MATLAB.

Continuing with the example based on 2500 simulations and 2500 corresponding individual spot size distributions2722, the complete Monte Carlo analysis, e.g., the collective results of the ray tracing across all 2500 simulated patient, furnished 67500 (2500 simulations with 27 spots each) discrete spot size values, within a full surgical envelope sized 200 μm azimuthal×500 μm circumferential×400 μm depth. With reference toFIG.31, an example slice of a final spot size distribution2726at a particular depth z in the surgical volume resulting from the above described Monte Carlo analysis is shown. The horizontal axis is the circumferential extent in microns of the envelope and the vertical axis in microns is the azimuthal extent. The modeled spot is shown from 5 μm (blue) to about 20 μm (red). The blue areas indicate the places in the surgical volume where the projected spot size is about 5 μm whereas the red areas indicate places where the spot size is as great as 15 μm. In principle, blue areas need less laser energy to treat tissue, while red areas need more laser energy. Larger spot sizes correspond to higher energy levels. The final spot size distribution2704may be represented in the form of a look up table.

At block2606ofFIG.26, having obtained a final spot size distribution for the target volume of ocular tissue, an energy value is assigned or mapped to the plurality of locations of the laser focus within the target volume of ocular tissue based on the final expected spot size at that location. Available energy parameter information, such as shown in Table 6 below, may be used to assign an energy value to the plurality of locations of the focus. For example, a location have a spot size in the range of 5.00 to 9.99 μm would be assigned an energy level of 0.6 μJ.

TABLE 6AssignedSpot Diameter (μm)Energy (μJ)5.00 to 9.990.610.00 to 14.992.415.00 to 19.995.320.00 to 24.999.4

While the generated look up table2704for the modeled target volume of ocular tissue2804is only for a portion of the circumference of the irido-corneal angle, the same look up table2704may be applied to all locations around the entire circumference of the irido-corneal angle. In other words, the forgoing process of generating the look up table does not have to be repeated for different rotational locations around the circumference of the irido-corneal angle. Alternatively, the entire method ofFIG.26may be repeated for one or more additional target volumes within ocular tissue of the irido-corneal angle. For example, with reference toFIG.28, the process may be repeated for a number of adjacent additional modeled target volumes2804around a portion of the circumference of the irido-corneal angle. The portion of the circumference may be characterized in degrees, e.g., 90°, 180°, 270°, 360°, etc., around the entire circumference of the irido-corneal angle.

FIG.31is a schematic block diagram of an apparatus3100corresponding to the look up table generator2702ofFIG.27. The apparatus3100is configured to execute instructions related to the look up table generation processes described above with reference toFIGS.26-30. The apparatus3100may be embodied in any number of processor-driven devices, including, but not limited to, a server computer, a personal computer, one or more networked computing devices, a microcontroller, and/or any other processor-based device and/or combination of devices.

The apparatus3100may include one or more processing units3102configured to access and execute computer-executable instructions stored in at least one memory3104. The processing unit3102may be implemented as appropriate in hardware, software, firmware, or combinations thereof. A hardware implementation may be a general purpose processor, a digital signal processor (DSP), an application specific integrated circuit (ASIC), a microprocessor, a microcontroller, a field programmable gate array (FPGA), a System-on-a-Chip (SOC), or any other programmable logic component, discrete gate or transistor logic, discrete hardware components, or any combination thereof, or any other suitable component designed to perform the functions described herein. Software or firmware implementations of the processing unit3102may include computer-executable or machine-executable instructions written in any suitable programming language to perform the various functions described herein.

The memory3104may include, but is not limited to, random access memory (RAM), flash RAM, magnetic media storage, optical media storage, and so forth. The memory3104may include volatile memory configured to store information when supplied with power and/or non-volatile memory configured to store information even when not supplied with power. The memory3104may store various program modules, application programs, and so forth that may include computer-executable instructions that upon execution by the processing unit3102may cause various operations to be performed. The memory3104may further store a variety of data manipulated and/or generated during execution of computer-executable instructions by the processing unit3102.

The apparatus3100may further include one or more interfaces3106that facilitate communication between the apparatus and one or more other apparatuses. For example, the interface3106may be configured to receive patient data to be used by a clinical model simulator. The interface3106is also configured to transmit generated look up tables to the control system100ofFIG.23. Communication may be implemented using any suitable communications standard. For example, a LAN interface may implement protocols and/or algorithms that comply with various communication standards of the Institute of Electrical and Electronics Engineers (IEEE), such as IEEE 802.11.

The memory3104may store various program modules, application programs, and so forth that may include computer-executable instructions that upon execution by the processing unit3102may cause various operations to be performed. For example, the memory3104may include an operating system module (O/S)3108that may be configured to manage hardware resources such as the interface3106and provide various services to operations executing on the apparatus3100.

The memory3104stores operation modules such as a clinical model simulator module3110, an optics model simulator module3112, an anatomical anchor locator module3114, ray tracing module3122, a spot size distribution module3116, a mapping module3118, and a look up table module3120. These modules may be implemented as appropriate in software or firmware that include computer-executable or machine-executable instructions that when executed by the processing unit3102cause various operations to be performed, such as the operations described above with reference toFIGS.26-30. Alternatively, the modules may be implemented as appropriate in hardware. A hardware implementation may be a general purpose processor, a DSP, an ASIC, a FPGA or other programmable logic component, discrete gate or transistor logic, discrete hardware components, or any combination thereof, or any other suitable component designed to perform the functions described herein.