Patent Publication Number: US-2018042771-A1

Title: Epithelial ablation systems and methods

Description:
CROSS-REFERENCES TO RELATED APPLICATIONS 
     The present application claims the priority benefit of U.S. provisional patent application No. 62/373,217, filed on Aug. 10, 2016, which is incorporated by reference as if fully set forth herein. The present application is related to U.S. Pat. Nos. 6,068,625; 6,558,373; 7,931,644; 8,292,878; 8,926,600; and 9,295,584, the content of each of which is incorporated herein by reference. 
    
    
     BACKGROUND 
     Embodiments of the present invention relates generally to the contouring of optical surfaces. More specifically, embodiments relate to devices, systems, and methods for contouring optical surfaces with laser beams. Merely by way of example, devices systems and methods according to embodiments of the present invention are described with reference to the treatment of eyes during photorefractive keratectomy (PRK) and other laser vision treatment procedures. 
     Known laser eye surgery procedures generally employ an ultraviolet or infrared laser to remove a microscopic layer of stromal tissue from the cornea of the eye. The laser typically removes a selected shape of the corneal tissue, often to correct refractive errors of the eye. Ultraviolet laser ablation results in photodecomposition of the corneal tissue, but generally does not cause significant thermal damage to adjacent and underlying tissues of the eye. The irradiated molecules are broken into smaller volatile fragments photo-chemically, directly breaking the intramolecular bonds. 
     Laser ablation procedures can remove the targeted stroma of the cornea to change the cornea&#39;s contour for varying purposes, such as for correcting myopia, hyperopia, astigmatism, and the like. Control over the distribution of ablation energy across the cornea may be provided by a variety of systems and methods, including the use of ablatable masks, fixed and moveable apertures, controlled scanning systems, eye movement tracking mechanisms, and the like. In known systems, the laser beam often comprises a series of discrete pulses of laser light energy, with the total shape and amount of tissue removed being determined by the shape, size, location, and/or number of laser energy pulses impinging on the cornea. A variety of algorithms may be used to calculate the pattern of laser pulses used to reshape the cornea so as to correct a refractive error of the eye. Known systems make use of a variety of forms of lasers and/or laser energy to effect the correction, including infrared lasers, ultraviolet lasers, femtosecond lasers, frequency multiplied solid-state lasers, and the like. The lasers of these laser systems typically deliver a series of laser beam pulses during a treatment. 
     Known corneal correction treatment methods have generally been successful in correcting standard vision errors, such as myopia, hyperopia, astigmatism, and the like. By customizing an ablation pattern based on wavefront measurements, it may be possible to correct minor aberrations so as to reliably and repeatedly provide visual acuity greater than 20/20. Such detailed corrections will benefit from an extremely accurate ablation of tissue. 
     With many laser ablation procedures, the epithelium is generally removed so that the permanent optical correction can be ablated into the stroma and/or Bowman&#39;s membrane. With PRK the epithelium is removed to expose Bowman&#39;s membrane and/or the stroma. Epithelial removal has been accomplished mechanically and with laser ablation of the epithelial layer. Mechanical removal of the epithelial layer can be accomplished with mechanical scraping of the epithelial tissue layer to expose Bowman&#39;s membrane and/or the stroma. Another mechanical approach is to remove the epithelium with a brush. With Laser-Assisted Sub-Epithelial Keratectomy (LASEK), the epithelial layer is removed from the cornea as a sheet so that the layer can be replaced following the ablation of stromal tissue. Although these mechanical methods of epithelial removal have been successful clinically, mechanical removal of the epithelium takes time and can be perceived by the patients as invasive because the surgeon will touch the front surface of the eye with surgical instruments. Even though topical anesthesia is often applied to the cornea so that the patient cannot feel the surgeon touching his or her cornea, the patient can become nervous while the surgeon touches the front surface of the eye with the instruments, possibly delaying the procedure. 
     Laser ablation of the epithelium, also referred to as trans-epithelial ablation, can be less invasive and faster than mechanical approaches to removal of the epithelium. However, in some instances currently known approaches for laser ablation of the epithelium may be less than ideal, and in some instances the epithelial layer may not be ablated uniformly. Thus, a surgeon will often mechanically scrape the epithelium after laser removal of the epithelium to ensure that no residual epithelial debris remains before ablating stromal tissue. 
     For these and other reasons, it would be desirable to provide improved trans-epithelial ablation and/or stromal ablation techniques. Embodiments of the present invention provide solutions to at least some of these outstanding needs. 
     BRIEF SUMMARY 
     Embodiments of the present invention encompass systems and methods for ablating tissue in response to characteristics of the cornea, for example the corneal epithelial layer. The characteristics of the cornea can be used so as to improve the accuracy of the ablation and/or correction of the eye. In one aspect, embodiments include a method for treating a region of a cornea of an eye using a laser, the region of the cornea including an epithelial layer and a stromal layer. The method includes receiving an epithelial thickness map corresponding to the eye, receiving an epithelial basis data corresponding to an epithelial laser pulse ablation profile, ablating the epithelial layer with a first epithelial arrangement of laser beam pulses based on the epithelial thickness map and the epithelial basis data, receiving a crossover signal, and terminating the first epithelial arrangement of laser beam pulses in response to the crossover signal. In another aspect, embodiments include a system for treating a region of a cornea of an eye using a laser, the region of the cornea including an epithelial layer and a stromal layer. The system includes a laser configured to perform laser eye surgery and a processor. The processor is configured to receive an epithelial thickness map corresponding to the eye, receive an epithelial basis data corresponding to an epithelial laser pulse ablation profile, cause the laser to ablate the epithelial layer with a first epithelial arrangement of laser beam pulses based on the epithelial thickness map and the epithelial basis data, receive a crossover signal, and cause the laser to terminate the first epithelial arrangement of laser beam pulses in response to the crossover signal. In yet another aspect, a non-transitory computer-readable medium is disclosed that stores instructions that, when executed by a processor, cause the processor to receive an epithelial thickness map corresponding to the eye, receive an epithelial basis data corresponding to an epithelial laser pulse ablation profile, ablate the epithelial layer with a first epithelial arrangement of laser beam pulses based on the epithelial thickness map and the epithelial basis data, receive a crossover signal, and terminate the first epithelial arrangement of laser beam pulses in response to the crossover signal. 
     In one aspect, embodiments of the present invention encompass methods for treating a region of a cornea of an eye using a laser. The region of the cornea can include an epithelial layer disposed over a stromal layer. Exemplary methods can include receiving, at a processor system, an epithelial thickness map of the eye, receiving, at the processor system, an epithelial layer pulse repetition rate induction signal, receiving, at the processor system, an epithelial basis data corresponding to an epithelial laser pulse ablation profile, receiving, at the processor system, a stromal basis data corresponding to a stromal laser pulse ablation profile, and executing, using the processor system, computer executable code stored on a non-transitory computer readable medium. The computer executable code can include instructions that when executed on the processor system cause the laser to ablate the epithelial layer with a first epithelial arrangement of laser beam pulses at a first epithelial pulse repetition rate, where the first epithelial arrangement of laser beam pulses includes a first individual laser pulse corresponding to the epithelial basis data and to ablate the epithelial layer with a second epithelial arrangement of laser beam pulses at a second epithelial pulse repetition rate, where the second epithelial arrangement of laser beam pulses includes a second individual laser pulse corresponding to the epithelial basis data. The computer executable code can also include instructions that when executed on the processor system cause the laser to ablate the stromal layer with a stromal arrangement of laser beam pulses at a stromal pulse repetition rate, where the stromal arrangement includes a third individual laser pulse corresponding to the stromal basis data. The instructions can be based on the epithelial thickness map of the eye and the epithelial layer pulse repetition rate induction signal. In this way, by ablating the epithelial and stromal layers, exemplary methods involve treating the eye of the patient using the laser. In some cases, the second epithelial arrangement of laser beam pulses includes a number of laser pulses within a range from 50 pulses to 250 pulses. In some cases, the first epithelial pulse repetition rate is within a range from 18 Hz to 22 Hz, the second epithelial pulse repetition rate is within a range from 5 Hz to 6 Hz, and the stromal pulse repetition rate is a variable repetition rate. In some cases, the variable repetition rate has a maximum rate of 1000 Hz. In some cases, the first epithelial pulse repetition rate is within a range from 10 Hz to 1000 Hz, and the second epithelial pulse repetition rate is within a range from 5 Hz to 10 Hz. In some cases, the first epithelial arrangement of laser beam pulses includes a first laser beam pulse centered at a first position on the eye and a second laser beam pulse centered at a second position on the eye. In some cases, the first position is different from the second position. 
     In another aspect, embodiments of the present invention encompass systems for treating a region of a cornea of an eye using a laser. The region of the cornea can include an epithelial layer disposed over a stromal layer. Exemplary systems can include a first input that receives an epithelial thickness map of the eye, a second input that receives an epithelial layer pulse repetition rate induction signal, a third input that receives an epithelial basis data corresponding to an epithelial laser pulse ablation profile, a fourth input that receives a stromal basis data corresponding to a stromal laser pulse ablation profile, and a processor system. In some cases, systems may also include a laser. Systems may also include computer executable code stored on a non-transitory computer readable medium. The computer executable code can include instructions that when executed on the processor system cause the laser to ablate the epithelial layer with a first epithelial arrangement of laser beam pulses at a first epithelial pulse repetition rate, where the first epithelial arrangement of laser beam pulses includes a first individual laser pulse corresponding to the epithelial basis data, and with a second epithelial arrangement of laser beam pulses at a second epithelial pulse repetition rate, where the second epithelial arrangement of laser beam pulses includes a second individual laser pulse corresponding to the epithelial basis data. The computer executable code can also include instructions that when executed on the processor system cause the laser to ablate the stromal layer with a stromal arrangement of laser beam pulses at a stromal pulse repetition rate, where the stromal arrangement includes a third individual laser pulse corresponding to the stromal basis data. The instructions can be based on the epithelial thickness map of the eye and the epithelial layer pulse repetition rate induction signal. In some cases, the second epithelial arrangement of laser beam pulses includes a number of laser pulses within a range from 50 pulses to 250 pulses. In some cases, the first epithelial pulse repetition rate is within a range from 18 Hz to 22 Hz, the second epithelial pulse repetition rate is within a range from 5 Hz to 6 Hz, and the stromal pulse repetition rate is a variable repetition rate. In some cases, the variable repetition rate has a maximum rate of 1000 Hz. In some cases, the first epithelial pulse repetition rate is within a range from 10 Hz to 1000 Hz, and the second epithelial pulse repetition rate is within a range from 5 Hz to 10 Hz. In some cases, the first epithelial arrangement of laser beam pulses includes a first laser beam pulse centered at a first position on the eye and a second laser beam pulse centered at a second position on the eye. The first position can be different from the second position. 
     In yet another aspect, embodiments of the present invention encompass methods for treating a region of a cornea of an eye. The region of the cornea can include an epithelial layer disposed over a stromal layer. Exemplary methods can include receiving, at a processor system, an epithelial thickness parameter of the eye, receiving, at the processor system, an operator input designating a percentage of epithelial tissue for removal, receiving, at the processor system, an epithelial basis data corresponding to an epithelial laser pulse ablation profile, and executing, using the processor system, computer executable code stored on a non-transitory computer readable medium. The computer executable code can include instructions that when executed on the processor system cause the laser to ablate the epithelial layer with an epithelial arrangement of laser beam pulses. The epithelial arrangement of laser beam pulses can include a first individual laser pulse corresponding to the epithelial basis data, where the epithelial arrangement of laser pulses effective to remove the percentage of epithelial tissue. The instructions can be based on the epithelial thickness map of the eye and the operator input. Methods may also include manually removing a remaining portion of the epithelial layer. In this way, by ablating the epithelial layer to remove the percentage of epithelial tissue and manually removing a remaining portion of the epithelial layer, exemplary methods involve treating the eye of the patient using the laser. In some cases, the epithelial layer has a thickness, and the percentage of epithelial tissue corresponds to a percentage of the thickness of the epithelial layer. In some cases, the percentage is within a range from 50 percent to 95 percent. In some cases, the epithelial arrangement of laser beam pulses includes a first laser beam pulse centered at a first position on the eye and a second laser beam pulse centered at a second position on the eye. The first position can be different from the second position. In some cases, the epithelial thickness parameter comprises an epithelial thickness map of the eye. In some cases, the epithelial thickness parameter comprises an estimate of epithelial thickness of the eye. 
     In still another aspect, embodiments of the present invention encompass systems for treating a region of a cornea of an eye. The region of the cornea can include an epithelial layer disposed over a stromal layer. Exemplary systems can include a first input that receives an epithelial thickness parameter of the eye, a second input that receives an operator input designating a percentage of epithelial tissue for removal, a third input that receives an epithelial basis data corresponding to an epithelial laser pulse ablation profile, and a processor system. In some cases, systems can include a laser. Systems can also include computer executable code stored on a non-transitory computer readable medium. The computer executable code can include instructions that when executed on the processor system cause the laser to ablate the epithelial layer with an epithelial arrangement of laser beam pulses. The epithelial arrangement of laser beam pulses can include a first individual laser pulse corresponding to the epithelial basis data. The epithelial arrangement of laser pulses can be effective to remove the percentage of epithelial tissue. The instructions can be based on the epithelial thickness map of the eye and the operator input. In some cases, the computer executable code includes instructions that when executed on the processor system cause the system to provide a prompt to an operator to proceed with manual removal of a remaining portion of the epithelial layer. In some cases, the epithelial layer has a thickness, and the percentage of epithelial tissue corresponds to a percentage of the thickness of the epithelial layer. In some cases, the percentage is within a range from 50 percent to 95 percent. In some cases, the epithelial arrangement of laser beam pulses includes a first laser beam pulse centered at a first position on the eye and a second laser beam pulse centered at a second position on the eye. The first position can be different from the second position. In some cases, the epithelial thickness parameter includes an epithelial thickness map of the eye. In some cases, the epithelial thickness parameter includes an estimate of epithelial thickness of the eye. 
     In a further aspect, embodiments of the present invention encompass methods for treating a region of a cornea of an eye using a laser. The region of the cornea can include an epithelial layer disposed over a stromal layer. Exemplary methods can include receiving, at a processor system, an epithelial thickness map of the eye, receiving, at the processor system, a refractive optical property of the eye, receiving, at the processor system, an epithelial basis data corresponding to an epithelial laser pulse ablation profile, receiving, at the processor system, a stromal basis data corresponding to a stromal laser pulse ablation profile, and executing, using the processor system, computer executable code stored on a non-transitory computer readable medium. The computer executable code can include instructions that when executed on the processor system cause the laser to ablate the epithelial layer with an epithelial arrangement of laser beam pulses, where the epithelial arrangement of laser beam pulses includes a first individual laser pulse corresponding to the epithelial basis data, and the epithelial arrangement of laser beam pulses is based on the epithelial thickness map. The computer executable code can also include instructions that when executed on the processor system cause the laser to ablate the stromal layer with a first stromal arrangement of laser beam pulses, where the first stromal arrangement of laser beam pulses includes a second individual laser pulse corresponding to the epithelial basis data, and where the first stromal arrangement of laser beam pulses is effective to remove an amount of stromal tissue so as to produce a uniform anterior stromal surface. The computer executable code can also include instructions that when executed on the processor system cause the laser to ablate the stromal layer with a second stromal arrangement of laser beam pulses, where the second stromal arrangement of laser beam pulses includes a third individual laser pulse corresponding to the stromal basis data, and the second stromal arrangement of laser beam pulses is based on the refractive optical property of the eye. In this way, by ablating the epithelial and stromal layers, exemplary methods involve treating the eye of the patient using the laser. In some cases, the first stromal arrangement of laser beam pulses is effective to remove a scar present on the stromal layer of the cornea. In some cases, the epithelial arrangement of laser beam pulses includes a first laser beam pulse centered at a first position on the eye and a second laser beam pulse centered at a second position on the eye. The first position can be different from the second position. 
     In still yet another aspect, embodiments of the present invention encompass systems for treating a region of a cornea of an eye using a laser. The region of the cornea can include an epithelial layer disposed over a stromal layer. Exemplary systems can include a first input that receives an epithelial thickness map of the eye, a second input that receives a refractive optical property of the eye, a third input that receives an epithelial basis data corresponding to an epithelial laser pulse ablation profile, a fourth input that receives a stromal basis data corresponding to a stromal laser pulse ablation profile, and a processor system. In some cases, a system may include a laser. Systems may also include computer executable code stored on a non-transitory computer readable medium. The computer executable code can include instructions that when executed on the processor system cause the laser to ablate the epithelial layer with an epithelial arrangement of laser beam pulses, where the epithelial arrangement of laser beam pulses includes a first individual laser pulse corresponding to the epithelial basis data, and the epithelial arrangement of laser beam pulses is based on the epithelial thickness map. The computer executable code can also include instructions that when executed on the processor system cause the laser to ablate the stromal layer with a first stromal arrangement of laser beam pulses, where the first stromal arrangement of laser beam pulses includes a second individual laser pulse corresponding to the epithelial basis data, and the first stromal arrangement of laser beam pulses is effective to remove an amount of stromal tissue so as to produce a uniform anterior stromal surface. The computer executable code can also include instructions that when executed on the processor system cause the laser to ablate the stromal layer with a second stromal arrangement of laser beam pulses, where the second stromal arrangement of laser beam pulses includes a third individual laser pulse corresponding to the stromal basis data, and the second stromal arrangement of laser beam pulses is based on the refractive optical property of the eye. In some cases, the first stromal arrangement of laser beam pulses is effective to remove a scar present on the stromal layer of the cornea. In some cases, the epithelial arrangement of laser beam pulses includes a first laser beam pulse centered at a first position on the eye and a second laser beam pulse centered at a second position on the eye. The first position can be different from the second position. 
     In one aspect, embodiments of the present invention provide a method for treating a region of a cornea of an eye. The region comprises an epithelial layer disposed over a stromal layer. A thickness of the epithelial layer is measured, for example mapped, in the region of the cornea. The region is irradiated with laser beam pulses to ablate the epithelial layer of the region in response to the epithelial thickness. 
     In some embodiments, an optical property of the eye is mapped, and the region is irradiated in response to the mapped optical property and the mapped epithelial thickness. The optical property of the eye can be mapped at locations distributed in two dimensions across the pupil of the eye, and the thickness of the epithelium can be mapped at locations distributed in two dimensions. The stromal layer can be ablated in response to the mapped epithelial layer thickness, and the map of epithelial thickness can be registered with an iris of the eye. 
     In some embodiments, an arrangement of laser beam pulses is determined using the mapped epithelial thickness and irradiation of the region is initiated using the determined arrangement. The epithelial layer can be ablated in response to the mapped epithelial thickness to expose at least one of the stromal layer or a Bowman&#39;s membrane. Delivery of the epithelial arrangement of pulses can be interrupted in response to a tissue fluorescence of at least one of the epithelial layer, a Bowman&#39;s membrane or the stromal layer. 
     In some embodiments, an optical property of the eye is determined and the region irradiated in response to the determined optical property of the eye and the mapped thickness of the epithelial layer. A first arrangement of laser beam pulses can be determined in response to the map of the epithelial layer and a second arrangement of laser beam pulses determined in response to the optical property of the eye. The first arrangement and the second arrangement may comprise locations of the laser beam pulses. 
     In some embodiments, the first arrangement of laser beam pulses may remove the epithelial layer to expose at least one of the stromal layer or a Bowman&#39;s membrane and the second arrangement of laser beam pulses may ablate a portion of the stromal layer to correct the optical property. Alternatively or in combination, the first arrangement of laser beam pulses may be combined with the second arrangement of laser beam pulses such that a portion of the second arrangement of laser beam pulses irradiates the epithelial layer and a portion of the first arrangement of laser beam pulses irradiates the stroma. In specific embodiments, the portion of the second arrangement that irradiates the epithelium may be interspersed among pulses of the first arrangement, and the portion of the first arrangement that irradiates the stroma may be interspersed among pulses of the second arrangement. 
     In some embodiments, energy is transmitted through the epithelial layer and/or reflected from an interface between the epithelial layer and the stromal layer while the region is mapped, and the energy reflected from the interface may comprise at least one of optical energy or ultrasound energy. 
     In another aspect, embodiments of the present invention provide a system to treat a region of a cornea of an eye, in which the region comprises an epithelial layer disposed over a stromal layer. The system comprises a device to measure a thickness of the epithelial layer, and a laser to generate a laser beam of an ablative radiation. A movable scan component is coupled to the laser to scan the laser beam over the region. A processor system is coupled to the laser and the movable scan component. The processor system comprises a tangible medium configured to arrange pulses of laser beam to ablate the epithelial layer of the region in response to the epithelial thickness. 
     In many embodiments the device to measure the thickness of the epithelial layer comprises at least one of an ultrasound array, an optical coherence tomography machine, a con-focal microscope or a Scheimpflug imaging system 
     In another aspect, embodiments of the invention provide a system to treat a region of a cornea of an eye. The region comprises an epithelial layer disposed over a stromal layer. The system comprises a device to map a thickness of the epithelial layer over the region of the cornea to generate a map of epithelial thickness over the region, and a laser to generate a laser beam of an ablative radiation. A movable scan component is coupled to the laser to scan the laser beam over the region. A processor system is coupled to the laser and the movable scan component. The processor system comprises a tangible medium configured to arrange pulses of laser beam to ablate the epithelial layer of the region in response to the map of epithelial thickness. 
     In some embodiments, the processor system is configured to ablate the epithelial layer in response to the epithelial layer map thickness to expose at least one of the stromal layer or a Bowman&#39;s membrane. The processor system can be configured control the laser and/or moveable scan component to ablate the stromal layer in response to the map of thickness of the epithelial layer. The processor system can be configured to determine a refractive optical property of the eye and irradiate the region in response to the determined optical property and the map of the thickness of the epithelial layer. 
     In specific embodiments, the refractive optical property device may comprise at least one of a trial lens, a phoropter, an auto-refractor, a spatially resolved refractometer, a corneal topographer, or a Hartmann-Shack wavefront sensor. The device to map the epithelial layer may comprise at least one of an ultrasound array, an optical coherence tomography machine, a confocal microscope or a Scheimpflug imaging system. 
     The processor system may be configured to register the map of epithelial thickness with an iris of the eye and adjust the arrangement of pulses in response to an orientation of the eye. 
     In some embodiments, the system includes an imaging system to form an image of a tissue auto-fluorescence of the cornea that is visible to a user, wherein the processor system is configured to interrupt delivery of the epithelial arrangement of pulses in response to user input while the user views the tissue auto-fluorescence. 
     In another aspect, embodiments of the present invention provide a method for treating a region of a cornea of an eye. The eye comprises an epithelial layer over a stromal layer. An epithelial basis profile is determined for the epithelial layer and a stromal basis profile for the stromal layer. The stromal basis profile is different from the epithelial basis profile. An epithelial arrangement of laser beam pulses can be determined that corresponds to ablation of the epithelial layer of the region to a target epithelial ablation profile. The region is irradiated with the epithelial arrangement. 
     In some embodiments, the epithelial arrangement can be determined in response to the epithelial basis profile and the target ablation profile. The epithelial basis profile may correspond to tissue removed with an epithelial laser beam pulse to the epithelial layer, and the stromal basis profile may correspond to tissue removed with a stromal laser beam pulse to the stromal layer. In specific embodiments, the epithelial arrangement may be determined with a plurality of epithelial basis profiles that correspond to epithelial tissue ablated with a plurality of sizes of the laser beam. 
     In some embodiments, an arrangement of laser beam pulses for ablation of Bowman&#39;s membrane may be determined. 
     In specific embodiments, a thickness of the epithelial layer of the region can be mapped to generate a map of epithelial thickness over the region, and the epithelial arrangement determined in response to the map of epithelial thickness over the region. 
     In some embodiments, a stromal arrangement of laser beam pulses corresponds to ablation of a stromal layer of the region to a target stromal ablation profile. The stromal arrangement can be determined with a stromal basis profile that corresponds to stromal tissue removed with laser beam pulses to the stromal layer. The region can be irradiated with the stromal arrangement of laser beam pulses to contour the region. The stromal arrangement may be determined in response to the stromal basis profile and the target stromal ablation profile. The stromal arrangement can be determined with a plurality of stromal basis profiles that correspond to stromal tissue ablated with a plurality of sizes of the laser beam. An optical property of the eye over the region can be mapped to generate an optical property profile over the region, and the stromal arrangement is determined in response to the optical property profile. The epithelial arrangement of pulses can be delivered to the epithelial layer and the stromal arrangement of pulses is delivered to the stromal layer. 
     In some embodiments, the epithelial arrangement of pulses can be combined with the stromal arrangement of pulses, and several pulses of the epithelial arrangement are delivered to the stromal layer and several pulses of the epithelial arrangement are delivered to the epithelial layer. In specific embodiments, the several pulses of the epithelial arrangement that are delivered to the stromal layer may be interspersed among several pulses of the stromal arrangement that are delivered to the stromal layer. The several pulses of the stromal arrangement that are delivered to the epithelial layer may be interspersed among several pulses of the epithelial arrangement that are delivered to the epithelial layer 
     In some embodiments of the present invention, a method is provided for treating a region of a cornea of an eye with an epithelial layer over a stromal layer and an epithelial basis profile determined for the epithelial layer and a stromal basis profile determined for the stromal layer. An epithelial arrangement of laser beam pulses is determined that corresponds to ablation of the epithelial layer of the region to a target epithelial ablation profile. The stromal basis profile is different from the epithelial basis profile. The region is irradiated with the epithelial arrangement. 
     In some embodiments, a stromal arrangement of laser beam pulses is determined that corresponds to ablation of a stromal layer of the region to a target stromal ablation profile. The region can be irradiated with the stromal arrangement of laser beam pulses to contour the region. The epithelial arrangement of pulses may be combined with the stromal arrangement of pulses, and several pulses of the epithelial arrangement delivered to the stromal layer and several pulses of the epithelial arrangement delivered to the epithelial layer. 
     In another aspect, embodiments of the present invention provide a system to treat a region of a cornea of an eye. The eye comprises an epithelial layer over a stromal layer. The system includes a laser to generate a beam and the laser beam comprises pulses of an ablative radiation, and a movable scan component to scan the laser beam over the region of the cornea to ablate the region. The system may include a processor system coupled to the laser and the movable scan component to scan the laser beam over the region. The processor system comprises a tangible medium configured to store an epithelial basis profile for the epithelial layer and a stromal basis profile for the stromal layer, the epithelial basis profile is different from the stromal basis profile. The processor system can be configured to determine an epithelial arrangement of the laser beam pulses in response to a target epithelial ablation profile and the epithelial basis profile. 
     In some embodiments, a peripheral portion of the epithelial basis profile corresponds to concave surface curvature ablated with a pulse of the laser beam and an inner portion of the basis profile corresponds to convex surface curvature ablated with the laser beam pulse. The epithelial basis profile may correspond to tissue removed with an epithelial laser beam pulse to the epithelial layer, and the stromal basis profile corresponds to tissue removed with a stromal laser beam pulse to the stromal layer. The processor system can be configured to combine the epithelial arrangement of laser beam pulses with the epithelial basis profile to determine a calculated epithelial tissue ablation profile and compare the calculated profile with the target profile. In specific embodiments, the processor system comprises a plurality of epithelial basis profiles that correspond to sizes of the laser beam. 
     In some embodiments, the processor system is configured to determine a stromal arrangement of the laser beam pulses in response to a target stromal ablation profile and the stromal basis profile. The processor system can be configured to combine the stromal arrangement of laser beam pulses with the stromal basis profile to determine a calculated stromal tissue ablation profile and compare the calculated stromal ablation profile with the target stromal ablation profile. In specific embodiments, the processor system comprises a plurality of ablation basis profiles that correspond to sizes of the laser beam. 
     In some embodiments, the processor system is configured to determine at least one of the epithelial arrangement or the stromal arrangement in response to an optical property map of the region. The processor system can be configured to deliver the epithelial arrangement of pulses to the epithelial layer and the stromal arrangement of pulses to the stromal layer. In specific embodiments, the epithelial arrangement of pulses may be combined with the stromal arrangement of pulses, and several pulses of the epithelial arrangement are delivered to the stromal layer and several pulses of the stromal arrangement are delivered to the epithelial layer. 
     In some embodiments, the processor system is configured to store the epithelial arrangement of pulses and the stromal arrangement of pulses in a treatment table comprising a sequence of pulses. The treatment table sequence can comprise several smaller pulses before several larger pulses to expand the beam from the smaller pulses to the larger pulses several times during the treatment. 
     In some embodiments, the processor system comprises a tangible medium configured to store Bowman&#39;s basis profile for ablation of Bowman&#39;s layer, and the Bowman&#39;s basis profile may be different from the stromal basis profile and the epithelial basis profile. The processor system can be configured to determine a Bowman&#39;s arrangement of the laser beam pulses in response the Bowman&#39;s basis profile. 
     In another aspect, embodiments of the present invention provide a method for treating a region of a cornea of an eye in which the eye comprises a Bowman&#39;s layer over a stromal layer. A Bowman&#39;s basis profile is provided for the Bowman&#39;layer and a stromal basis profile is determined for the stromal layer. The stromal basis profile may be different from the Bowman&#39;s basis profile. A Bowman&#39;s arrangement of laser beam pulses is determined that corresponds to ablation of the Bowman&#39;s layer of the region to a target Bowman&#39;s ablation profile. The region is irradiated with the Bowman&#39;s arrangement. 
     In some embodiments, a stromal arrangement of laser beam pulses is determined that correspond to ablation of a stromal layer of the region to a target stromal ablation profile. The region may be irradiated with the stromal arrangement of laser beam pulses to contour the region. The stromal arrangement can be determined in response to the stromal basis profile and the target stromal ablation profile. 
     In a further aspect, embodiments of the present invention provide a system to treat a region of a cornea of an eye in which the eye comprises a Bowman&#39;s layer over a stromal layer. The system comprises a laser to generate a beam in which the beam comprises pulses of an ablative radiation. The system also comprises a movable scan component to scan the laser beam over the region of the cornea to ablate the region. A processor system may be coupled to the laser and the movable scan component to scan the laser beam over the region. The processor system may comprise a tangible medium configured to store a Bowman&#39;s basis profile for the Bowman&#39;s layer and a stromal basis profile for the stromal layer. The Bowman&#39;s basis profile may be different from the stromal basis profile, and the processor system may be configured to determine a Bowman&#39;s arrangement of the laser beam pulses in response to a target Bowman&#39;s ablation profile and the Bowman&#39;s basis profile. 
     In some embodiments, the processor system may be configured to determine a stromal arrangement of the laser beam pulses in response to a target stromal ablation profile and the stromal basis profile. The processor system may be configured to combine the stromal arrangement of laser beam pulses with the stromal basis profile to determine a calculated stromal tissue ablation profile and compare the calculated stromal ablation profile with the target stromal ablation profile. The processor system may comprise a plurality of ablation basis profiles that correspond to sizes of the laser beam. 
     In another aspect, embodiments of the present invention provide a method for contouring a region of a cornea of an eye. The region comprises an epithelial layer disposed over a stromal layer. A thickness of an epithelial layer of the region is mapped. A refractive optical property of the region is determined, and a desired optical profile to correct the refractive optical property is determined. A healed profile of the epithelial layer over the stromal layer is determined in response to the desired optical profile and the mapped epithelial layer thickness. The stromal layer is ablated to a profile in response to the healed epithelial layer profile to contour the region and correct the optical property of the eye. 
     In some embodiments, the optical property comprises at least one of a manifest refraction, a cycloplegic refraction, an auto-refraction, a Zernike coefficient, a Fourier coefficient or a wavefront elevation map. An epithelial component of the optical property and a remainder component of the optical property can be determined. The epithelial component corresponds to the mapped thickness of the epithelial layer. The epithelial component may be subtracted from the optical property to determine the remainder component. The stromal layer profile can be ablated in response to the remainder component and the healed epithelial layer component. 
     In some embodiments, a healed profile of the stromal layer is determined, and the stromal layer ablation profile determined in response to the healed stromal layer profile and the healed epithelial layer profile. 
     In another aspect, embodiments of the present invention provide a system for contouring a region of a cornea of an eye. The region comprises the epithelial layer disposed over a stromal layer. The system comprises a laser to generate an ablative laser beam, and an epithelial thickness mapping device to map a thickness of an epithelial layer of the region. A processor system comprises a tangible medium configured to determine a desired optical profile to correct an optical property of the eye. The processor system is configured to determine a healed profile of the epithelial layer over the stromal layer in response to the desired optical profile and the mapped epithelial layer thickness. The processor system is coupled to the laser to ablate a profile in the stromal layer in response to the healed epithelial layer profile to contour the region and correct the optical property of the eye. In specific embodiments, the optical property comprises at least one of a manifest refraction, a cycloplegic refraction, an auto-refraction, or a wavefront elevation map. 
     In some embodiments, the processor system can be configured to determine an epithelial component of the optical property and a remainder component of the optical property, and the epithelial component corresponds to the mapped thickness of the epithelial layer. The processor system can be configured to subtract the epithelial component from the optical property to determine the remainder component. The processor system may be configured to ablate the stromal layer profile in response to the remainder component and the healed epithelial component. 
     In some embodiments, the processor system is configured to determine a healed profile of the stromal layer. The processor system may be configured to determine the stromal layer ablation profile in response to the healed stromal layer profile and the healed epithelial layer profile. 
     For a fuller understanding of the nature and advantages of the present invention, reference should be had to the ensuing detailed description taken in conjunction with the accompanying drawings. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         FIG. 1A  is a perspective view of a laser ablation system for incorporating embodiments of the present invention. 
         FIG. 1B  illustrates profiles of mapped tissue structures of an eye, according to embodiments of the present invention. 
         FIG. 1C  illustrates an ablation of a region of a cornea of an eye using an arrangement of scanning laser beam pulses of varying diameter applied over a region of a cornea of an eye, according to embodiments of the present invention. 
         FIGS. 2 and 3  schematically illustrate a laser beam delivery system for selectively directing a laser beam onto the corneal tissue, according to embodiments of the present invention. 
         FIG. 4  is a function block diagram illustrating a control architecture of an ablation system as in  FIG. 1 , according to embodiments of the present invention. 
         FIG. 5A  is a schematic illustration of a system for mapping refractive optical properties of an eye, mapping epithelial thickness of the eye, and ablating the eye with an arrangement of laser beam pulses, according to embodiments of the present invention. 
         FIG. 5B  is a schematic illustration of epithelial basis data used to determine an arrangement of laser beam pulses to ablate an epithelial layer to a targeted epithelial ablation profile, according to embodiments of the present invention. 
         FIG. 5C  is a schematic illustration of stromal basis data used to determine an arrangement of laser beam pulses to ablate a stromal layer to a targeted stromal ablation profile, according to embodiments of the present invention. 
         FIG. 5D  is a schematic illustration of Bowman&#39;s basis data used to determine an arrangement of laser beam pulses to ablate Bowman&#39;s layer to a targeted stromal ablation profile, according to embodiments of the present invention. 
         FIG. 5E  is a schematic illustration of a target epithelial ablation profile and an estimated epithelial ablation profile determined by combining the epithelial basis data with an epithelial arrangement of laser beam pulses, according to embodiments of the present invention. 
         FIG. 5F  is a schematic illustration of a target stromal ablation profile and an estimated stromal ablation profile determined by combining the stromal basis data with a stromal arrangement of laser beam pulses, according to embodiments of the present invention. 
         FIG. 5G  is a schematic illustration of a target Bowman&#39;s ablation profile and an estimated Bowman&#39;s ablation profile determined by combining the Bowman&#39;s basis data with a Bowman&#39;s arrangement of laser beam pulses, according to embodiments of the present invention. 
         FIG. 6A  is a schematic illustration of a profile map of corneal epithelial thickness, according to embodiments of the present invention. 
         FIG. 6B  is a schematic illustration of a profile map of refractive optical properties of the eye, according to embodiments of the present invention. 
         FIG. 6C  is a schematic illustration of a stromal ablation profile map to correct refractive optical properties of the eye in response to the refractive optical properties profile map as in  FIG. 6B , according to embodiments of the present invention. 
         FIG. 6D  is a schematic illustration of layers of corneal tissue ablated based on mapping the thickness of the epithelium and mapping the refractive optical properties of the eye, according to embodiments of the present invention. 
         FIG. 7A  is a schematic illustration of a profile map of estimated healed corneal epithelial thickness following ablation of the profile map to correct refractive optical properties of the eye, according to embodiments of the present invention. 
         FIG. 7B  is a schematic illustration of a stromal ablation profile map in response to the map of estimated corneal epithelial thickness following ablation as in  FIG. 7A , the profile map of corneal epithelial thickness as in  FIG. 6A  and the profile map of refractive optical properties of the eye as in  FIG. 6B , according to embodiments of the present invention. 
         FIG. 8A  is a simplified schematic illustration of an epithelial arrangement of pulses in accordance with embodiments of the present invention. 
         FIG. 8B  is a simplified schematic illustration of a stromal arrangement of pulses in accordance with embodiments of the present invention. 
         FIG. 8C  is a simplified schematic illustration of an epithelial treatment table that comprises epithelial arrangement, according to embodiments of the present invention. 
         FIG. 8D  is a simplified schematic illustration of a stromal treatment table that comprises stromal arrangement, according to embodiments of the present invention. 
         FIG. 8E  is a simplified schematic illustration of a sequential treatment table that comprises epithelial sequence combined stromal sequence, according to embodiments of the present invention. 
         FIG. 8F  is a simplified schematic illustration of an interleaved treatment table that comprises epithelial sequence interleaved with stromal sequence, according to embodiments of the present invention. 
         FIG. 9  is a flow chart that schematically illustrates a method of ablating the eye, according to embodiments of the present invention. 
         FIGS. 10A to 10H  show examples of images of epithelial fluorescence, according to embodiments of the present invention. 
         FIG. 11  shows a plot of image intensity for epithelium removal with images as in  FIGS. 10A to 10H . 
         FIG. 12  is a simplified schematic illustration of a sequential treatment table that comprises epithelial sequence ablation pulse instructions combined with stromal sequence ablation pulse instructions, according to embodiments of the present invention. 
         FIG. 13  depicts aspects of a treatment method that includes administration of epithelial sequence ablation pulses combined with administration of stromal sequence ablation pulses, according to embodiments of the present invention. 
         FIG. 14  is a simplified schematic illustration of a sequential treatment table that comprises epithelial sequence ablation pulse instructions combined with stromal sequence ablation pulse instructions, according to embodiments of the present invention. 
         FIG. 15  depicts aspects of a treatment method that includes administration of epithelial sequence ablation pulses combined with administration of stromal sequence ablation pulses, according to embodiments of the present invention. 
         FIGS. 16 and 16A-16C  depict aspects of a treatment method that includes administration of epithelial sequence ablation pulses combined with administration of stromal sequence ablation pulses, according to embodiments of the present invention. 
         FIG. 17  depicts aspects of a treatment method that includes administration of epithelial sequence ablation pulses combined with administration of stromal sequence ablation pulses, according to embodiments of the present invention. 
         FIG. 18  depicts aspects of an exemplary computer system according to an embodiment of the present invention. 
     
    
    
     DETAILED DESCRIPTION 
     Embodiments of the present invention can be particularly useful for enhancing the accuracy and efficacy of laser eye surgical procedures, such as photorefractive keratectomy (PRK), phototherapeutic keratectomy (PTK), and the like. In some instances, embodiments of the present invention can provide enhanced optical accuracy of refractive procedures and improved patient comfort during the procedure by improving removal of the corneal epithelium. Hence, while the system and methods of exemplary embodiments of the present invention are described primarily in the context of a laser eye surgery system for treating a cornea of the eye, it should be understood the techniques of the present invention may be adapted for use in alternative ablation procedures. 
     The techniques disclosed herein can be readily adapted for use with existing laser systems. By providing a more rapid (and hence, for example, less error-prone) methodology for correcting optical errors of an eye, embodiments of the present invention facilitates sculpting of the cornea so that treated eyes may regularly receive a desired optical correction having improved vision with minimal discomfort to a patient. 
     Referring now to  FIG. 1A , a laser eye surgery system  10  for incorporating embodiments of the present invention includes a laser  12  that produces a laser beam  14 . Laser  12  is optically coupled to laser delivery optics  16 , which directs laser beam  14  to an eye of patient P. A delivery optics support structure (not shown here for clarity) extends from a frame  18  supporting laser  12 . An input device  20  is used to align laser system  10  with patient P. A microscope  21  is mounted on the delivery optics support structure. Microscope  21  comprises an imaging system to image a cornea of eye E. The laser eye surgery system  10  may include a display  23  that provides an image of eye E that is visible to the user. A video camera  25  can be optically coupled to microscope  21  to provide an image of the eye E on the display as seen through the microscope. 
     Microscope  21  transmits visible light, and the operator can view tissue auto-fluorescence of the epithelial layer while the laser ablates corneal tissue. The operator can interrupt the treatment in response to penetration of the epithelial layer, for example by lifting a foot switch pedal. Microscope  21  may comprise at least one lens to form an optical image of the tissue fluorescence that is visible to the operator such that the operator can detect penetration of the epithelial layer based on the optical feedback. In some embodiments, video camera  25  comprises a camera sensitive to visible light and at least a portion of the epithelial fluorescence comprises visible light, such that epithelial fluorescence can be seen with video camera  25 . In some embodiments, a second video camera  25 A can be coupled to microscope  21 . Second camera  25 A comprises a sensor sensitive to UV light to detect epithelial fluorescence. Second camera  25 A can be triggered off the laser fire signal, such that each pulse of the treatment can be shown on the display, for example fluorescence from individual pulse  23 P. Second video camera  25 A may comprise an electronic shutter synchronized to the laser trigger such that the shutter is open for no more than about 1 ms, for example no more than 100 μs, or even no more than 50 μs, when the laser fires to enhance visibility of the epithelial fluorescence. Although a microscope is shown, in some embodiments a camera lens can be used to image the tissue fluorescence, such that the image of the tissue fluorescence can be shown on the display. 
     In some embodiments, the laser pulses may be sorted such that the user can see penetration of the epithelial layer, as described in U.S. Pat. App. No. 60/865,342, filed Nov. 10, 2006, entitled, “Operator-Controlled Scanning Laser Procedure Designed for Large-Area Epithelium Removal,” the full disclosure of which is incorporated herein by reference. 
     In some embodiments the laser may automatically detect penetration of the epithelial layer as described in U.S. Pat. Nos. 5,505,724; 6,019,755; and 6,293,939 entitled “Epithelium Removal”. 
     In many embodiments, a sudden reduction in fluorescence, for example either an average amount or a number of pixels of an image of fluorescence, can be measured and used to find and/or determine breakthrough, for example penetration, of the epithelial layer, for example when the measured fluorescence decreases from a first value above a threshold fluorescence amount to a second value below the threshold fluorescence amount so as to indicate penetration and/or breakthrough of the epithelial layer. In response to the detected penetration and/or breakthrough, the treatment algorithm and/or treatment program may stop ablation for safety and/or may change treatment modes, for example to selectively ablate epithelium and/or to perform a refractive ablation of the stroma. Systems and methods of detecting at least one of penetration, breakthrough or clearance of the epithelial layer and automated removal of the epithelium in response to epithelial fluorescence are described in U.S. Pat. No. 8,926,600, the full disclosure of which is incorporated herein by reference. In various embodiments, the laser eye surgery system  10  includes at least some portions of a STAR S4 IR™ Excimer Laser System with Variable Spot Scanning (VSS™). In some embodiments, the laser eye surgery system  10  includes at least some portion of a WaveScan WaveFront® System or an iDesign® System available from AMO Manufacturing USA, LLC, Milpitas, Calif., the Wavelight® Allegretto laser system, Wavelight® Analyzer II, and Wavelight® Topolyzer™ diagnostic system commercially available from Alcon, a Novartis division, of Forth Worth; Tex., the Zyoptix® Systems commercially available from Bausch &amp; Lomb of Bridgewater, N.J.; the EC-5000 Series of excimer laser systems commercially available from NIDEK of Gamagori, Japan, the OPD Scan III also available from NIDEK; and the MEL 80™ Excimer Laser, WASCA™ analyzer, and Atlas 9000 system, all commercially available from Carl Zeiss Meditec, Inc. of Dublin, Calif. One embodiment includes a WaveScan system with a deformable mirror. An alternate embodiment of a wavefront measuring system is described in U.S. Pat. No. 6,271,915, the full disclosure of which is incorporated herein by reference. It is appreciated that any wavefront aberrometer could be employed for use with embodiments of the present invention. Relatedly, embodiments of the present invention encompass the implementation of any of a variety of optical instruments provided by Abbott Medical Optics Inc., including the iDesign system, and the like. 
     Relatedly, embodiments of the present invention encompass the implementation of any of a variety of optical instruments provided by WaveFront Sciences, Inc., including the COAS wavefront aberrometer, the ClearWave contact lens aberrometer, the CrystalWave IOL aberrometer, and the like. Embodiments of the present invention may also involve wavefront measurement schemes such as a Tscherning-based system, which may be provided by Alcon. Embodiments of the present invention may also involve wavefront measurement schemes such as a ray tracing-based system, which may be provided by Tracey Technologies, Corp. 
     Laser eye surgery system  10  may comprise an eye tracker  19 . Eye tracker  19  may comprise, for example, an eye tracker as commercially available in the STAR S4 IR™ Excimer Laser System with Variable Spot Scanning (VSS™). Eye tracker  19  may comprise optical components microscope  21 . The eye tracking system may comprise at least some optical components separate from the microscope, for example as described in U.S. Pat. No. 6,322,216. Eye tracker  19  can be in communication with the embedded computer so as to offset the position of the laser beam pulse in response to a measured position of the eye. The processor may comprise a processor system with at least one processor, for example a plurality of processors, such as a processor for tracking the eye, a processor to control the laser and at least one processor to control positions of scanning elements, sensors and laser firing. The processor system may comprise a distributed processor system with a first processor to calculate a treatment table, for example at a research facility, and a second processor, for example of the laser system, to ablate the eye with the treatment table from the first processor. In some cases, one processor may be implemented in or coupled with a diagnostic device (e.g. wavefront aberrometer) and another processor may be implemented in or coupled with a laser delivery device. In some cases, a separate processor may be implemented in or coupled with a device that measures and/or calculates epithelial thickness. In some cases, a separate processor may be implemented in or coupled with a device that calculates an epithelial removal treatment. In some cases, a single processor or processor system can perform any of the calculations, determinations, or method steps disclosed herein. In some cases, systems as disclosed herein may include one or more processors or processor systems. 
     The display  23  may comprise windows to show images of the eye, for example a first window  23 W and a second window  23 A. First window  23 W can be coupled to video camera  25  to show the image of the eye E as seen through the operating microscope. First window  23 W may show structures visible to the operator, for example a reticule  23 R, and the image of the eye including the iris and pupil. Video camera  25  may comprise a color video camera to show a color image of the eye to the operator on the display. Second window  23 A can be coupled to second video camera  25 A. The second video camera  25 A can be coupled to a frame grabber of the embedded processor to grab an image for each pulse of the laser treatment and display the image from each pulse in second window  23 A of the display, so as to minimize dropped frames and facilitate detection of penetration through the epithelium. The camera synchronized to the laser beam pulse can improve epithelial fluorescence imaging and may be used for detection of penetration where the display is shown to an operator and/or where the laser pulse firing is stopped automatically. Although reference is made to a video camera, the fluorescence sensor can comprise many known sensors sensitive to fluorescence such as at least one of an area sensor, a line sensor, a CCD array, a gated image intensifier, photomultiplier tube, a photodiode, a phototransistor or a cascade detector. 
     While the input device  20  is here schematically illustrated as a joystick, it should be understood that a variety of input mechanisms may be used. Suitable input mechanisms may include trackballs, touch screens, foot-pedals or a wide variety of alternative pointing devices. Still further alternative input mechanisms include keypads, data transmission mechanisms such as an Ethernet, intranet, internet, a modem, or the like. 
     Laser  12  generally comprises an excimer laser, ideally comprising an argon-fluorine laser producing pulses of laser light having a wavelength of approximately  193  nm. The pulses of laser light typically have a fixed pulse duration having a full width half maximum (FWHM) of about  15  nanoseconds during a treatment. Laser  12  is preferably designed to provide a feedback stabilized fluence at the patient&#39;s eye, delivered via delivery optics  16 . Embodiments of the present invention may also be useful with alternative sources of ultraviolet or infrared radiation, particularly those adapted to controllably ablate the corneal tissue without causing significant damage to adjacent and/or underlying tissues of the eye. The laser system may include, but is not limited to, excimer lasers such as argon-fluoride excimer lasers (producing laser energy with a wavelength of about 193 nm), solid state lasers, including frequency multiplied solid state lasers such as flash-lamp and diode pumped solid state lasers. Exemplary solid state lasers include UV solid state lasers (approximately 193-215 nm) such as those disclosed in U.S. Pat. Nos. 5,144,630 and 5,742,626; Borsurtky et al., “ Tunable UV Radiation at Short Wavelengths  (188-240  nm )  Generated by Sum Frequency Mixing in Lithium Borate,” Appl. Phys.  61:529-532 (1995), and the like. The laser energy may comprise a beam formed as a series of discreet laser pulses. A variety of alternative lasers might also be used. Hence, although an excimer laser is the illustrative source of an ablating beam, other lasers may be used in embodiments of the present invention. 
     Laser  12  and delivery optics  16  generally direct laser beam  14  to the eye E of patient P under the direction of a computer  22 . Computer  22  will often selectively adjust laser beam  14  to expose portions of the cornea to the pulses of laser energy so as to effect a predetermined sculpting of the cornea and alter the refractive characteristics of the eye. In some embodiments, both laser  14  and the laser delivery optical system  16  will be under computer control of processor system  22  to effect the desired laser sculpting process, with the processor system effecting (and optionally modifying) the pattern of laser pulses. In some embodiments, a treatment plan is developed to treat a layer of tissue, and the treatment plan can be defined with a pattern of laser beam pulses. For example, a treatment plan to ablate the epithelial layer may comprise a pattern of laser beam pulses applied to the epithelial layer, and a treatment plan to ablate the stromal tissue may comprise a pattern of stromal laser beam pulses applied to the stromal layer. The pattern of pulses may by summarized in machine readable data of tangible media  29  in the form of a treatment table. Although tangible media  29  is illustrated having a particular form factor in  FIG. 1A , it should be understood that any form of tangible media may store information indicating the pattern of pulses used to ablate the stromal tissue and/or the epithelial layer, or any other machine instructions and/or data discussed herein. The treatment table may be adjusted according to feedback input into processor system  22  from an automated image analysis system (which automated image analysis system may be, for example, manually installed into the processor system by a system operator) in response to feedback data provided from an ablation monitoring system feedback system. Such feedback might be provided by integrating the wavefront measurement system described below with the laser treatment system  10 , and processor system  22  may continue and/or terminate a sculpting treatment in response to the feedback, and may optionally also modify the planned sculpting based at least in part on the feedback. 
     Laser beam  14  may be adjusted to produce the desired sculpting using a variety of alternative mechanisms. The laser beam  14  may be selectively limited using one or more variable apertures. An exemplary variable aperture system having a variable iris and a variable width slit is described in U.S. Pat. No. 5,713,892. The laser beam may also be tailored by varying the size and offset of the laser spot from an axis of the eye, as described in U.S. Pat. Nos. 5,683,379, and 6,203,539. 
     Still further alternatives are possible, including scanning of the laser beam over a surface of the eye and controlling the number of pulses and/or dwell time at each location, as described, for example, by U.S. Pat. No. 4,665,913; using masks in the optical path of laser beam  14  which ablate to vary the profile of the beam incident on the cornea; hybrid profile-scanning systems in which a variable size beam (typically controlled by a variable width slit and/or variable diameter iris diaphragm) is scanned across the cornea; or the like. The computer programs and control methodology for these laser pattern tailoring techniques are well described in the patent literature. 
     Additional components and subsystems may be included with laser system  10 , as should be understood by those of skill in the art. For example, spatial and/or temporal integrators may be included to control the distribution of energy within the laser beam, as described in U.S. Pat. No. 5,646,791. An ablation effluent evacuator/filter and other ancillary components of the laser surgery system which are not necessary to an understanding of the invention need not be described in detail for an understanding of the present invention. 
     Processor system  22  may comprise (or interface with) a conventional PC system including the standard operator interface devices such as a keyboard, a display monitor, and the like. Processor system  22  typically includes an input device such as a magnetic or optical disk drive, an internet connection, or the like. Such input devices will often be used to download a computer executable code from a tangible storage media  29  embodying any of the methods of the present invention. Tangible storage media  29  may take the form of a floppy disk, an optical disk, a data tape, a volatile or non-volatile memory, or the like, and the processor system  22  includes the memory boards and other standard components of modern computer systems for storing and executing this code. Tangible storage media  29  may optionally embody wavefront sensor data, wavefront gradients, a wavefront elevation map, a treatment map, a corneal topography map, a measurement of refraction of the eye, pupil images of the eye such as iris registration data, epithelial map data, and/or an ablation table. 
       FIG. 1B  illustrates profiles of mapped tissue structures of an eye, according to embodiments of the present invention. An eye E comprises an epithelium or epithelial layer, Bowman&#39;s membrane, a stroma/stromal layer under Bowman&#39;s membrane, and an endothelial layer. As Bowman&#39;s membrane is substantially collagenous and has a poorly defined posterior boundary with the stromal layer, at least a portion of Bowman&#39;s membrane can be considered a part of the stromal layer in some embodiments of the present invention. Eye E includes an iris that defines a pupil. The epithelial thickness above the stromal layer and Bowman&#39;s membrane is mapped and has as a central thickness E 1  and a peripheral thickness E 2 . In some embodiments, several thickness measurements are made along a tissue section to profile the thickness along the section, and several sections are measured to provide a map of epithelial thickness along two dimensions over the pupil of the eye. In some embodiments, several optical coherence tomography (hereinafter “OCT”)scans are made along tissue sections to map the epithelium. In some embodiments, Scheimpflug images are measured along tissue sections and combined to make a three dimensional map. The maps can be shown as three dimensional maps of corneal thickness with the first two dimensions corresponding to transverse positions on the eye and the third dimension corresponding to the thickness of the epithelial layer at locations along the first two dimensions. In some embodiments, the thickness of additional structures are mapped, for example thickness of the stromal layer defined by a distance from Bowman&#39;s membrane to the endothelial layer, a thickness of the crystalline lens and/or a length of the eye. 
     An ablation of a region of a cornea of an eye using an arrangement of pulses  14   a - 14   e  of a scanning laser beam is illustrated in  FIG. 1C . The arrangement of pulses is applied to positions over a region  15  of a cornea C of an eye E. As illustrated in  FIG. 1A , pulses  14   e  and  14   d  overlap. A dimension across pulse  14   c  is smaller than a dimension across pulse  14   b . The arrangement of pulses  14   a  to  14   e  corresponds to the coordinate position and size of each pulse. The arrangement can be ordered to define a sequential series of pulses  14   a  to  14   e  that is sequentially applied to eye E in accordance with a treatment table listing. The treatment table lists the coordinates and sizes of the laser beam for each pulse. Mathematically, an arrangement of pulses in a treatment table may correspond to a pulse instruction vector (hereinafter “Hy”) that represents the laser instruction for each pulse. Systems and methods for determining an arrangement of laser beam pulses with basis functions are described in U.S. Pat. No. 7,008,415, the full disclosure of which is incorporated herein by reference. 
     A sequential series of pulses that ablates the epithelial layer to a desired shape can be referred to as an epithelial series of pulses. In some embodiments, an epithelial series of pulses can be used to ablate the epithelial layer, for example to provide access to at least one of the stromal layer or Bowman&#39;s membrane. The epithelial series of pulses may be arranged to ablate the epithelial layer in response to the mapped thickness of the epithelial layer. 
     An additional ablation procedure can then be ablated into at least one of the stromal corneal tissue or Bowman&#39;s membrane to provide a refractive correction with a stromal arrangement of pulses. A sequential series of pulses that ablates the stromal layer can be referred to as a stromal series of pulses. 
     In some embodiments, some of the pulses may simultaneously ablate epithelial tissue and Bowman&#39;s membrane and/or stromal tissue, and such pulses may be referred to as crossover pulses. Crossover pulses may occur when the epithelial layer is partially removed and the laser beam pulse irradiates residual epithelial tissue and exposed Bowman&#39;s membrane tissue and/or stromal tissue with the same pulse. As the corneal stroma, like the Bowman&#39;s membrane, includes substantially acellular collagenous tissue and collagenous tissue fibers, ablation of Bowman&#39;s membrane can be modeled with stromal ablation basis functions. Also, in some embodiments, Bowman&#39;s membrane may comprise a thickness of two to three microns such that modeling of Bowman&#39;s tissue as stromal tissue may have a minimal impact on error in the ablated shape. 
     In some embodiments, the epithelial layer can be ablated with epithelial pulses until penetration of the stroma is detected with crossover epithelial pulses that simultaneously ablate epithelial tissue and Bowman&#39;s tissue and/or stromal tissue, and the operator may pause the treatment. The treatment can be resumed with stromal pulses and the stromal layer can be subsequently ablated with stromal pulses. The epithelium may be allowed to grow back over the stroma following stromal ablation with stromal pulses. 
     The treatment table can be sorted in many ways. In some embodiments, the epithelial series of pulses is applied to the epithelial layer and the stromal series of pulses applied to the stromal layer. In some embodiments, the pulses are sorted such that some of the pulses from the stromal series are applied to the epithelial layer and some of the pulses from the epithelial series are applied to the stromal layer. The stromal pulses may be combined with the epithelial pulses such that the stromal pulses are interspersed, or mixed, between the epithelial pulses by sorting, such that many epithelial pulses are applied to the stromal tissue layer after the epithelial layer is ablated and many stromal pulses are applied to the epithelial layer before the stromal layer is ablated. 
     In some embodiments, the epithelium and stroma can be ablated to remove corneal haze with minimal intended impact on the refraction of the eye. 
     Referring now to  FIG. 2 , laser beam delivery system  16  for directing laser beam  14  at eye E will often include a number of mirrors  30 , as well as one or more beam homogenizers. The laser beam homogenizers can even (or otherwise tailor) the laser energy distribution across the laser beam with spatial and temporal integration. Spatial integration can include overlapping portions of the laser beam with prisms, diffractive optics, lenses and the like. In some embodiments, a hexagonal array of prisms  36  separates laser beam  14  into a plurality of beamlets, which may partially overlap on eye E to smooth edges of the ablation or “crater” from each pulse of the laser beam. Temporal integration can include moving the beam, for example with rotation with dove prisms, K-mirrors, cylindrical lens pairs and the like. In some embodiments, temporal integrator  32 , may comprise a dove prism. Laser  12  will often comprise an excimer laser as described above. Apparatus for laser beam homogenization are described in U.S. Pat. Nos. 5,646,791; 5,912,775; 6,816,316 and 7,206,132. 
     In some embodiments, a variable aperture  34  changes a diameter and/or slot width profile of laser beam  14 . In specific embodiments, the variable aperture includes both a variable diameter iris and a variable width slot. Variable aperture  34  may comprise a variable diameter iris and/or a plurality of apertures on a movable structure such as a plate or wheel. In some embodiments that scan the laser beam over the eye with offset of the laser beam, a variable sized circular aperture may provide correction of astigmatism and wavefront aberrations, optionally without the variable slot. 
     Referring now to  FIGS. 2 and 3 , an offset module  38  may include motors  40  which vary an angular offset of an offset lens  42 , and which also change the radial orientation of the offset. Hence, offset module  38  can selectively direct laser beam  14  at a desired lateral region of the cornea. A structure and method for using laser beam delivery system  16  and offset module  38  are more fully described in U.S. Pat. Nos. 6,984,227; 6,331,177; 6,203,539; 5,912,775; and 5,646,791. In some embodiments, the offset module may comprise scanners with movable mirror that are controlled with galvanometer current measurements, as described in U.S. Pat. Nos. 4,718,418; 4,665,913 and 5,480,396. 
     Referring now to  FIG. 4 , a control system of a laser system  10  is schematically illustrated according to the principles of the present invention. A processor system  22  enables precise control of laser system  10  to sculpt a surface shape specified in a laser treatment table  52 . A processor system  22 , which generally comprises a PC workstation, makes use of a computer program stored on a tangible media  29  to generate treatment table  52 . Processor system  22  may include a library  44  of treatments and treatment tables as described in U.S. Pat. Nos. 6,245,059; and 7,077,838. In some embodiments, processor system  22  may additionally include several basis data profiles and programs to calculate simulated ablation shapes and determine a sequence of laser beam pulses. An embedded computer  58  within laser system  10  is in electronic communication with the PC workstation. Alternatively, a PC workstation may be embedded in the laser system and include an embedded processor card in communication with the PC workstation for directing the ophthalmic surgery. The eye tracker  19 , as described above, can be connected to embedded computer  58 . Video camera  25  and second video camera  25 A can be optically coupled to microscope  21 , as described above, and connected to display  23  to show images of the eye to the surgeon and/or system operator. 
     Embedded computer  58  is in electronic communication with a plurality of sensors  56  and a plurality of motor drivers  60 . The motor drivers  60  are coupled to the embedded computer  58  to vary the position and configuration of many of the optical components of the delivery optics  16  according to treatment table  52 . For example, first and second scanning axis  62 ,  64  control the position of the offset lens to move the beamlets over the surface of the cornea. Iris motor  66  controls the diameter of the overall beam, and in some cases, the length of light transmitted through a variable width slot. Similarly slot width driver  68  controls the width of the variable slot. Slot angle driver  70  controls rotation of the slot about its axis. Beam angle driver  72  controls rotation of the beam as effected by a temporal integrator as described above. Processor system  22  issues a command for laser  12  to generate a pulse of the laser beam  14  after the various optical elements have been positioned to create a desired crater on eye E. Treatment table  52  comprises a listing of all of the desired craters to be combined so as to effect a treatment therapy. 
     A timer  80  may be located on an add on card of processor system  22  and in some embodiments may comprise a Lab-PC-1200 model card having timers 8253/8254. The Lab-PC-1200 model card is available from National Instruments of Austin, Tex. In alternate embodiments, timer  80  is located externally to processor system  22 . The timer  80  is controlled by a computer program of processor system  22  and is adapted to measure time intervals. The laser  12  is electronically coupled to processor system  22 . Laser  12  fires upon a command issued from processor system  22  in response to a time interval measured by timer  80 . Processor system  22  varies the rate at which laser  12  fires during at least a portion of a treatment of an eye E. 
       FIG. 5A  is a schematic illustration of a system  200  for mapping refractive optical properties of an eye, mapping epithelial thickness of the eye, and ablating the eye with an arrangement of laser beam pulses, according to embodiments of the present invention. System  200  includes a refractive properties mapping device  210 . Refractive properties mapping device  210  can map refractive optical properties of the eye, for example wavefront elevation mapping of the refractive properties of the entire optical train of the eye extending from the cornea to the retina. System  200  includes an epithelial thickness mapping device  220 . Epithelial thickness mapping device  220  maps a thickness of the epithelial layer covering Bowman&#39;s membrane and the stroma. System  200  may include a corneal topography mapping device  230 . Corneal topography mapping device  230  maps a surface topography of the front surface of the cornea, for example with videokeratography. In some embodiments, system  200  includes the same device to perform both corneal epithelial mapping and corneal topography mapping. 
     System  200  includes a processor system  240 , with many of the components as described above. Processor system  240  includes epithelial basis data  242 , stromal basis data  252  and may comprise Bowman&#39;s basis data  262 . Epithelial basis data  242  includes ablation profiles for laser beam pulses to the epithelial layer that can be used to calculate the shape of tissue removed from the epithelial layer for an epithelial arrangement of laser beam pulses applied to the epithelial layer. Stromal basis data  252  includes ablation profiles for laser beam pulses to the stromal layer that can be used to calculate the shape of tissue removed from the stromal layer with a stromal arrangement of laser beam pulses applied to the stromal layer. Bowman&#39;s basis data  262  includes ablation profiles for laser beam pulses to Bowman&#39;s layer that can be used to calculate the shape of tissue removed from Bowman&#39;s layer with a Bowman&#39;s arrangement of laser beam pulses applied to Bowman&#39;s layer. System  200  includes a laser eye surgery system  250 . Laser eye surgery system  250  can include many of the components described above. 
     Processor system  240  receives as input mapped epithelial thickness profile data from device  220 , and mapped refractive property profile data from device  210 . Processor system  240  can receive input from many additional sources to determine the treatment for the patient, for example patient manifest refraction, age and keratometry. Processor system  240  uses the epithelial, stromal and/or Bowman&#39;s basis profile data to determine the arrangement of laser beam pulses, for example as a pulse instruction vector as described in U.S. Pat. No. 7,008,415, the full disclosure of which has been previously incorporated herein by reference. Processor system  240  outputs a laser treatment table to laser eye surgery system  250 . The laser eye surgery system uses coordinate references in the treatment table and sizes of the laser beam to treat the eye. 
     In some embodiments, processor system  240  may comprise a distributed processor network that includes a plurality of processors in electronic or other communication, for example of the Internet, an intranet and/or local area network with wireless communication. In specific embodiments, an operator can carry a floppy drive from one processor to another processor to effect communication among the processors of the processor system. In some embodiments, refractive properties mapping device  210  comprises a processor; epithelial thickness mapping device  220  comprises a processor; and corneal topography mapping device  230  comprises a processor and laser eye surgery system  250  comprises a processor. Processor system  240  may comprise the processors of any of the measurement devices and the laser eye surgery system. 
     Refractive properties mapping device  210  may comprise many devices that can be used to determine the refractive properties of the optical path of the eye from the front surface of the cornea to the retina with subjective and/or objective measurements. In some embodiments refractive properties mapping device  210  comprises a Hartmann Shack wavefront sensor, for example as described in U.S. Pat. Nos. 6,155,684; 6,264,328; 6,271,914; 6,271,915; and 7,036,934. In some embodiments, refractive properties mapping device  210  comprises a spatially resolved refractometer, for example as described in U.S. Pat. Nos. 5,258,791; 6,000,800; and 6,409,345. In some embodiments, the device to measure the eye may include objective measurements with a light probe beam, for example as described in U.S. Pat. No. 6,409,345, entitled “Method and Device for Synchronous Mapping of the Total Refraction Non-Homogeneity of the Eye and Its Refractive Components”; and U.S. Pat. No. 6,932,475, entitled “Device for Measuring Aberration Refraction of the Eye”. In some embodiments, the refractive optical properties of the eye may be measured with an interferometer, for example as described in U.S. Pat. No. 7,084,986, entitled “System for Measuring the Optical Image Quality of an Eye in a Contactless Manner”; and U.S. Pat. No. 6,922,250, entitled “Optical Multiplex Short Coherence Interferometry on the Eye”. In some embodiments, the optical property of the eye is measured with an autorefractor, for example as described in U.S. Pat. No. 7,001,020, entitled “Complete Autorefractor System in an Ultra-Compact Package”; and U.S. Pat. No. 5,329,322, entitled “Palm Size Autorefractor and Fundus Topographical Mapping Instrument”. The optical property of the eye determined with many of these devices can be determined as a wavefront elevation map, Zernike coefficients, and Fourier coefficients, for example as described in U.S. Pat. No. 6,299,311, entitled “Rapid, Automatic Measurement of the Eye&#39;s Wave Aberration; U.S. Pat. No. 7,175,278, entitled “Wavefront Reconstruction Using Fourier Transformation and Direct Integration”, and U.S. Pat. No. 7,168,807, entitled “Iterative Fourier Reconstruction for Laser Surgery and Other Optical Applications”. 
     Epithelial thickness mapping device  220  may comprise many devices that can used to determine a thickness of the epithelial layer. In some embodiments, epithelial mapping device  220  measures energy reflected from the interface of the epithelial layer with Bowman&#39;s membrane and/or the stroma. The reflected energy may comprise light energy and/or ultrasonic energy. In some embodiments epithelial thickness mapping device  220  comprises an OCT machine, for example as described in U.S. Pat. Nos. 5,491,524; 6,741,359; and 6,755,819. In some embodiments, the epithelial thickness mapping device may comprise a high frequency ultrasound array, for example as described in U.S. Pat. Nos. 6,315,727; 6,949,071; 7,048,690. Scheimpflug and other photography may also be used to map thickness of the epithelial layer U.S. Pat. Nos. 4,523,821; 5,512,965; 6,286,958; 6,588,903. In some embodiments, epithelial mapping device  220  may comprise a con-focal microscope, for example as described in U.S. Pat. Nos. 5,359,373 and 6,118,580. In some embodiments, epithelial mapping device  220  may measure a thickness of Bowman&#39;s membrane, and the thickness data of Bowman&#39;s membrane may be communicated within processor system  240  and used to determine an arrangement of laser beam pulses to ablate Bowman&#39;s membrane. 
     In some embodiments, epithelial mapping device  220  comprises an imaging system to image the iris of eye E while the epithelium is mapped. The mapped epithelial thickness profile can then be registered and/or stored with the epithelial thickness profile so as to permit registration of the mapped epithelium with the iris. The registration of the mapped epithelium can occur while the epithelial thickness is mapped and/or during ablation of the region of the eye. Examples of systems and methods to register an image of the iris of the eye during laser ablation are described in U.S. Pat. No. 7,044,602, entitled “Methods and Systems for Tracking a Torsional Orientation and Position of an Eye”. In some embodiments, the processor system may adjust the arrangement of laser beam pulses in real time in response to torsional alignment of the eye while the patient is treated with the therapeutic laser beam. 
     Corneal topography mapping device  230  may comprise many devices that can be used to measure and/or map topography of the corneal surface. In some embodiments corneal topography mapping device  230  can comprise a machine that analyzes images reflected from the eye to determine the topography map of the anterior surface of the cornea as described, for example, in U.S. Pat. Nos. 4,692,003; 4,863,260; 5,062,702; and 5,841,511. In some embodiments, corneal topography mapping device  230  comprises fluorescence that analyzes the position fluorescence from a pattern projected on the eye to determine the shape of the front surface of the eye as described, for example, in U.S. Pat. Nos. 4,761,071; 4,995,716; 5,159,361; 6,592,574; 6,613,041; and 6,666,857. In some embodiments, the system that maps one or more of the epithelial thickness, the refractive properties of the retina, and the corneal topography is not the same system as the system that applies the laser eye surgery. Thus, instead of actively performing these functions, the system  200  may instead receive that data (the refractive properties, epithelial thickness map, and/or corneal topography) pre-determined from another system and may perform laser eye surgery based on that data as described elsewhere herein. Stated differently, the refractive properties mapping device  210 , epithelial thickness mapping device  220 , and corneal topography mapping device  230  are considered optional in  FIG. 5A . 
       FIG. 5B  is a schematic illustration of epithelial basis data  242  used to determine an arrangement of laser beam pulses to ablate an epithelial layer with an epithelial ablation profile, according to embodiments of the present invention. Epithelial basis data  242  includes profiles of epithelial basis data for small, medium and large beam diameters, for example 2, 4 and 6 mm beam diameters respectively. A coordinate reference system  242 X,  242 Y, and  242 Z shows dimensions of the basis ablation profile data. Each of the profiles shows a characteristic ablation for a single pulse of the laser beam at the specified diameter. A peripheral portion of each basis ablation profile corresponds to a concave ablation in tissue and comprises concave surface curvature with localized negative optical power. An inner portion of each basis ablation profile may correspond to a concave, convex or flat localized ablation surface curvature in tissue depending on the size and characteristics of the laser beam and type of tissue ablated. In some embodiments, the inner portion can be concave with concave surface curvature, for example with 1 mm beam diameters and with Gaussian laser beam profiles. In some embodiments with flat top or uniform laser energy distribution laser beams with diameter greater than about 3 mm, the inner portion of the ablation may comprise localized flat and convex surface curvature while the peripheral portion of the ablation comprises localized concave surface curvature. In some embodiments, the inner portion comprises a flat central sub-portion with flat curvature (i.e. no curvature or zero curvature) and a peripheral inner sub-portion with convex curvature. 
     Small pulse ablation profile  242 A illustrates ablation profile data for a small diameter laser beam. Small diameter pulse ablation profile  242 A comprises an inner portion  246 A and an annular peripheral portion  244 A. Annular peripheral portion  244 A comprises a concave surface curvature ablated with a peripheral portion of the laser beam. Inner portion  246 A comprises a concave surface curvature ablated with a central portion of the laser beam. 
     Medium pulse ablation profile  242 B illustrates a profile for a medium diameter laser beam. Medium diameter pulse ablation profile  242 B comprises an inner portion  246 B and an annular peripheral portion  244 B. Annular peripheral portion  244 B comprises a concave surface ablated with a peripheral portion of the laser beam. Inner portion  246 B comprises flat and convex surface curvatures ablated with a central portion of the laser beam, and inner portion  246 B is ablated to a lesser depth than peripheral portion  244 B. Inner portion  246 B comprises a central sub-potion with flat curvature and a peripheral convex sub-portion with convex curvature. 
     Large pulse ablation profile  242 C illustrates a profile for a large diameter laser beam. Large diameter pulse ablation profile  242 C comprises an inner portion  246 C and an annular peripheral portion  244 C. Annular peripheral portion  244 C comprises a concave surface curvature ablated with a peripheral portion of the laser beam. Inner portion  246 C comprises flat and convex surface curvatures ablated with a central portion of the laser beam. Such profiles can be obtained with a uniform laser beam having a top hat energy distribution profile, although many laser beams and energy distributions can be used, for example multi-laser beam energy distribution profiles, for example as described in U.S. Pat. No. 6,984,227. Inner portion  246 C comprises a central sub-potion with flat curvature and a peripheral convex sub-portion with convex curvature. 
     Epithelial basis data  242  can be generated empirically with experimental measurements from patients. For example, the shape of epithelial tissue can be measured in situ with corneal topography on a population of patients who undergo trans-epithelial PRK. For each pulse diameter profile approximately 10 patients are measured. For example, with basis ablation profiles for each of 1, 2, 3, 4, 5 and 6 mm, 10 patients are measured for a total of 60 patients. Basis data for smaller sized laser beams may also be measured. The corneal epithelial layer may be measured prior to laser ablation with mapping as described above. The shape of the front surface of the cornea can be measured intra-operatively prior to ablation, and then measured subsequently during ablation with many of the corneal topography mapping devices described above. The shape of tissue removed with the fixed size laser beam is then measured for each patient to empirically determine the basis data for the fixed laser beam diameter used. The epithelial tissue can then be removed in many ways, for example mechanically and/or chemically and normal PRK performed. 
       FIG. 5C  is a schematic illustration of stromal basis data  252  used to determine an arrangement of laser beam pulses to ablate a stromal layer with a stromal ablation profile, according to embodiments of the present invention. Stromal basis data  252  can be obtained with many of the laser beams and methods described with respect to the epithelial ablation data. Stromal basis data  252  comprises small diameter pulse ablation profile  252 A, medium diameter pulse profile  252 B and large diameter pulse profile  252 C. In some embodiments the diameters of the small, medium and large diameter pulses are 2, 4 and 6 mm, respectively. 
     Small pulse ablation profile  252 A illustrates ablation profile data for a small diameter laser beam. Small diameter pulse ablation profile  252 A comprises an inner portion  256 A and an annular peripheral portion  254 A. Annular peripheral portion  254 A comprises a concave surface ablated with a peripheral portion of the laser beam. Inner portion  256 A comprises a concave surface curvature ablated with a central portion of the laser beam. 
     Medium pulse ablation profile  252 B illustrates a profile for a medium diameter laser beam. Medium diameter pulse ablation profile  252 B comprises an inner portion  256 B and an annular peripheral portion  254 B. Annular peripheral portion  254 B comprises a concave surface curvature ablated with a peripheral portion of the laser beam. Inner portion  256 B comprises flat and convex surface curvatures ablated with a central portion of the laser beam. Inner portion  256 B comprises a central sub-potion with flat curvature and a peripheral convex sub-portion with convex curvature. 
     Large pulse ablation profile  252 C illustrates a profile for a large diameter laser beam. Large diameter pulse ablation profile  252 C comprises an inner portion  256 C and an annular peripheral portion  254 C. Annular peripheral portion  254 C comprises a concave surface ablated with a peripheral portion of the laser beam. Inner portion  256 C comprises flat and convex surface curvatures ablated with a central portion of the laser beam. Inner portion  256 C comprises a central sub-potion with flat curvature and a peripheral convex sub-portion with convex curvature. 
     In some embodiments, the basis profiles for the epithelial layer and stromal layer are different for similar beam diameters. For example, the central depth of ablation can be different, and the size of the inner portion flat and convex curvatures may be different. 
       FIG. 5D  is a schematic illustration of Bowman&#39;s basis data  262  used to determine an arrangement of laser beam pulses to ablate a Bowman&#39;s layer with a Bowman&#39;s ablation profile, according to embodiments of the present invention. Bowman&#39;s basis data  252  can be obtained with many of the laser beams and methods described with respect to the epithelial and stromal ablation data. Bowman&#39;s basis data  262  comprises small diameter pulse ablation profile  262 A, medium diameter pulse profile  262 B and large diameter pulse profile  262 C. In some embodiments the diameters of the small, medium and large diameter pulses are 2, 4 and 6 mm, respectively. 
     Small pulse ablation profile  262 A illustrates ablation profile data for a small diameter laser beam. Small diameter pulse ablation profile  262 A comprises an inner portion  266 A and an annular peripheral portion  264 A. Annular peripheral portion  264 A comprises a concave surface ablated with a peripheral portion of the laser beam. Inner portion  266 A comprises a concave surface curvature ablated with a central portion of the laser beam. 
     Medium pulse ablation profile  262 B illustrates a profile for a medium diameter laser beam. Medium diameter pulse ablation profile  262 B comprises an inner portion  266 B and an annular peripheral portion  264 B. Annular peripheral portion  264 B comprises a concave surface curvature ablated with a peripheral portion of the laser beam. Inner portion  266 B comprises flat and convex surface curvatures ablated with a central portion of the laser beam. Inner portion  266 B comprises a central sub-potion with flat curvature and a peripheral convex sub-portion with convex curvature. 
     Large pulse ablation profile  262 C illustrates a profile for a large diameter laser beam. Large diameter pulse ablation profile  262 C comprises an inner portion  266 C and an annular peripheral portion  264 C. Annular peripheral portion  264 C comprises a concave surface ablated with a peripheral portion of the laser beam. Inner portion  266 C comprises flat and convex surface curvatures ablated with a central portion of the laser beam. Inner portion  266 C comprises a central sub-potion with flat curvature and a peripheral convex sub-portion with convex curvature. 
     In some embodiments, the basis profiles for the epithelial layer, stromal layer and Bowman&#39;s layer are different for the similar beam diameters. For example, the central depth of ablation can be different, and the size of the inner portion flat and convex curvatures may be different for each of the three tissue layers. 
       FIG. 5E  is a schematic illustration of a target epithelial ablation profile  270  and an estimated epithelial ablation profile  272  determined by combining the epithelial basis data with an epithelial arrangement of laser beam pulses, according to embodiments of the present invention. Target epithelial ablation profile  270  can be obtained in many ways; for example, by mapping the epithelium as described above, or by an operator inputting a desired depth of ablation for a uniform epithelial thickness. The processor system then uses the target ablation shape and the epithelial basis data profiles to determine an arrangement of laser beam pulses that will remove tissue to the target profile  270 . The processor system combines the arrangement of laser beam pulses with the profile of each laser beam pulse and adds the profiles for each pulse together to obtain the estimated epithelial ablation profile  272 . Although the estimated ablation profile  272  can be obtained in many ways, in an embodiment the estimated ablation profile is calculated by adding the epithelial ablation basis profile for each pulse of the treatment together with the other pulses of the treatment to determine the estimated ablation depth  272 . The arrangement of laser beam pulses for a given set of epithelial basis data and target ablation shape can be calculated in many ways, for example with techniques similar to those described in U.S. Pat. No. 7,008,415, the whole disclosure of which has been previously incorporated herein by reference. 
       FIG. 5F  is a schematic illustration of a target stromal ablation profile  280  and an estimated stromal ablation profile  282  determined by combining the stromal basis data with a stromal arrangement of laser beam pulses, according to embodiments of the present invention. Target stromal ablation profile  280  can be defined in many ways, for example, with wavefront elevation mapping of the refractive error along the optical path of the eye, manifest refraction of the eye, cycloplegic refraction of the eye, and autorefractor refraction of the eye. The processor system uses the target stromal ablation profile and the stromal basis profiles as described above to determine an arrangement of laser beam pulses to ablate the stromal tissue to the target stromal ablation profile  280 . Estimated stromal ablation profile  282  can be determined by combining the arrangement of laser beam pulses. For example, a calculation that uses the arrangement of laser beam pulses and the basis data for the stroma can be used to determine estimated stromal ablation profile  282 . The processor system may calculate the arrangement of laser beam pulses comprised in a treatment table in many ways; for example, with iterations using the treatment table to determine the arrangement of pulses so that a minimal residual error results between the target ablation profile and estimated ablation profile. Systems and methods for calculating a treatment table with basis data for a target ablation shape are described in U.S. Pat. No. 7,008,415, the full disclosure of which has been previously incorporated herein by reference. In some embodiments, localized laser ablation characteristics based on corneal topography mapping can be used and the treatment table calculated in response to corneal topography, for example as described in U.S. Pat. No. 7,083,609. 
       FIG. 5G  is a schematic illustration of a target Bowman&#39;s ablation profile  290  and an estimated Bowman&#39;s ablation profile  292  determined by combining the Bowman&#39;s basis data with a Bowman&#39;s arrangement of laser beam pulses, according to embodiments of the present invention. Target Bowman&#39;s ablation profile  290  can be obtained in many ways; for example, by measuring Bowman&#39;s with a con-focal microscope as described above, or by an operator inputting a desired depth of ablation through Bowman&#39;s membrane. The processor system then uses the target ablation shape and the Bowman&#39;s basis data profiles to determine an arrangement of laser beam pulses that will remove tissue to the target profile  290 . The processor system combines the arrangement of laser beam pulses with the profile of each laser beam pulse and adds the profiles for each pulse together to obtain the estimated Bowman&#39;s ablation profile  272 . Although the estimated ablation profile  272  can be obtained in many ways, in an embodiment the estimated ablation profile is calculated by adding the epithelial ablation basis profile for each pulse of the treatment together with the other pulses of the treatment to determine the estimated ablation depth  292 . The arrangement of laser beam pulses for a given set of epithelial basis data and target ablation shape can be calculated many ways, for example with techniques similar to those above. 
       FIG. 6A  is a schematic illustration of a mapped profile  310  of corneal epithelial thickness, according to embodiments of the present invention. Map profile  310  shows a depth or thickness of the corneal epithelial layer in microns across the corneal surface from −4 mm to +4 mm referenced in relation to the pupil of the eye. Mapped profile  310  shows the profile along one cross sectional slice of the corneal epithelial layer. In some embodiments, several parallel and perpendicular slices are obtained and the thickness of the epithelial layer is mapped along two dimensions of the eye. In some embodiments, the thickness of the epithelial layer can be three dimensional with two position dimensions along a pupil and/or cornea of the eye and a third dimension corresponding to thickness of the epithelium along the optical axis of the eye through the pupil. 
       FIG. 6B  is a schematic illustration of a wavefront map profile  320  of refractive optical properties of the eye, according to embodiments of the present invention. Profile  310  can be obtained in many ways including a wavefront mapping device that maps optical path difference or error across the pupil in relation to a plane wave. Epithelial thickness profile  310  can be subtracted from wavefront map profile  320  after the epithelial profile has been converted to optical path length. In some embodiments, the epithelial profile can be converted to optical path length by multiplying the profile by the quantity (n−1) where n is the index of refraction of the epithelium, about 1.377. The optical path length can then be converted to optical path difference (hereinafter “OPD”) relative to a plane by subtracting piston, or one or more other constants, from the optical path length such that the epithelial contribution to the refractive optical characteristic is determined. Epithelial contribution  322  can then be subtracted from wavefront map profile  320  to obtain a remainder portion  324 . In some embodiments, remainder portion  324  corresponds to curvature of the cornea, refractive power of the lens, and optical path length of the eye along the axis of the eye and the relative positions of the cornea, lens and retina along the optical path length of the eye. 
       FIG. 6C  is a schematic illustration of a stromal ablation profile  330  to correct refractive optical properties of the eye in response to the refractive optical properties profile map as in  FIG. 6B , according to embodiments of the present invention. Stromal ablation profile  330  can be calculated from wavefront map profile  320 . Stromal ablation profile  330  includes remainder portion profile  334 . Remainder portion profile  334  corrects the wavefront error of remainder portion  324 . Epithelial contribution profile  332  corrects epithelial contribution  322  to the wavefront map profile  320 . In some embodiments, the epithelial layer may heal over the ablation with the post-operative thickness profile the same as the pre-operative thickness profile, such that ablation of the stromal layer to correct epithelial contribution  322  can provide correction of the refractive optical properties of the eye. Hence, ablation of the epithelial contribution and remainder contribution can correct the optical errors of the eye. 
     In some embodiments, healing of the epithelial layer and stromal layer can impact the final shape of the eye and optical correction that the patient receives. Adjustment to the ablation profile in response to estimated healing may be used. 
       FIG. 6D  is a schematic illustration of layers of corneal tissue ablated based on mapping the thickness of the epithelium and mapping the refractive optical properties of the eye, according to embodiments of the present invention. Stromal ablation profile  330  is shown subtracted from the anterior stromal surface and/or Bowman&#39;s surface of the cornea. Epithelial thickness profile  310  is shown over the surface of the cornea. One will appreciate that in some embodiments the epithelium will heal following ablation in the stromal layer of profile  330 , and thickness profile  310  postoperatively will be changed in some embodiments. 
       FIG. 7A  is a schematic illustration of a healed epithelial profile  340  of healed corneal epithelial thickness following ablation of the profile map to correct refractive optical properties of the eye, according to embodiments of the present invention. Healed epithelial profile  340  is shown in relation to mapped epithelial profile  310 . A change in profile  342  shows the change in pre-operative epithelial profile  310  to post-operative epithelial profile  340 . Healed profile  340  and change in profile  342  and can be estimated based on empirical measurements of a patient population of patients who are treated. For example, a patient sample size of 100 patients can be selected and their epithelial thickness measured preoperatively and postoperatively to determine an estimate of postoperative thickness and/or change in thickness of the epithelial layer based on the pre-operative epithelial thickness mapping and ablation characteristics. An estimate of healed epithelial profile  340  can be used to modify the stromal ablation profile to determine an adjusted stromal ablation profile. The estimated healed profile can be in response to several patient variables, for example age, degree of myopia, degree hyperopia, degree of astigmatism, race and sex. The patient population can be increased or decreased as appropriate, depending on the number of variables and level of statistical significance and power. 
     Similar measurements and estimates can be made for stromal healing based on empirical data, and an estimated healed stromal profile determined. In some embodiments, the front surface of the stromal layer and/or Bowman&#39;s membrane is determined, for example by subtracting the mapped epithelial thickness profile from a corneal topography measurement. Pre-operative corneal topography measurements and post-operative corneal topography measurements can be made when the epithelial layer is mapped as described above, such that the stromal profile can be determined from the corneal topography and mapped epithelial layer. The stromal ablation profile can be adjusted in response to the changes in stromal profile and/or epithelial profile. 
       FIG. 7B  is a schematic illustration of an adjusted stromal ablation profile  350  in response to the map of estimated corneal epithelial thickness following ablation as in  FIG. 7A , the profile map of corneal epithelial thickness as in  FIG. 6A , and the profile map of refractive optical properties of the eye as in  FIG. 6B , according to embodiments of the present invention. Adjusted stromal ablation profile  350  includes a healed epithelial contribution  352  and remainder portion profile  334 . For comparison, stromal ablation profile  330  without the healing adjustment is also shown. Remainder portion profile  334  can be added to healed epithelial profile contribution  352  to obtain adjusted stromal ablation profile  350 . Adjusted stromal ablation profile  350  can then be used as a target stromal ablation profile and the arrangement of laser beam pulses solved to ablate the stroma with this profile. 
       FIG. 8A  is a simplified schematic illustration of an epithelial arrangement  802  of pulses in accordance with embodiments of the present invention. Epithelial arrangement  802  includes a diameter  830 , an x-coordinate  840 , y-coordinate  850  and a delay  860  for each pulse of the arrangement. A number of pulses  810  for each diameter and/or pulse number can also be specified for each pulse of the arrangement. A treatment table with delays, positions and diameters sorted to avoid tissue heating is described, for example, in U.S. Pat. No. 7,077,838. An illustrative epithelial treatment for epithelial mapping treatments may include 80 pulses of 1 mm diameter, 80 pulses of 2 mm diameter, 80 pulses of 3 mm diameter, and 80 pulses of 4 mm diameter. In some embodiments, each line in the treatment table corresponds to a single pulse of the laser beam, such that each pulse has its own position and delay, and the pulse position and delay can vary within each group of pulses. Although the illustrative embodiment can list positions for each pulse of the laser beam, the arrangement of pulses can be organized as a trajectory, or the like. 
       FIG. 8B  is a simplified schematic illustration of a stromal arrangement  804  of pulses in accordance with embodiments of the present invention. Stromal arrangement  804  includes diameter  830 , x-coordinate  840 , y-coordinate  850  and delay  860  for each pulse of the arrangement. Number of pulses  810  or pulse number is also be specified for each pulse of the arrangement. An illustrative stromal treatment to correct epithelial and remainder component aberrations may include 100 pulses of 1 mm diameter, 100 pulses of 2 mm diameter, 100 pulses of 3 mm diameter, and 100 pulses of 4 mm diameter. 
       FIG. 8C  is a simplified schematic illustration of an epithelial treatment table  806  that comprises epithelial arrangement  802 , according to embodiments of the present invention. Epithelial treatment table  806  comprises an epithelial sequence  870  of laser beam pulses, which is determined in response to epithelial mapping as described above. Epithelial arrangement  802  can be sorted to determine epithelial sequence  870 . Epithelial sequence  870  comprises pulses sorted such that the laser beam expands from small 1 mm diameter to larger 4 mm diameter four times during the ablation. 
       FIG. 8D  is a simplified schematic illustration of a stromal treatment table  808  that comprises stromal arrangement  804 , according to embodiments of the present invention. 
     Stromal treatment table  808  comprises a stromal sequence  880  of laser beam pulses, which is determined based on the optical properties of the eye and/or healing as described above. Stromal arrangement  804  can be sorted to determine stromal sequence  880 . Stromal sequence  880  comprises pulses sorted such that the laser beam expands from small 1 mm diameter to larger 4 mm diameter four times during the ablation. 
       FIG. 8E  is a simplified schematic illustration of a sequential treatment table  820  that comprises epithelial sequence  870  combined with stromal sequence  880 , according to embodiments of the present invention. Epithelial sequence  870  is located before stromal sequence  880  such that epithelial sequence  870  ablates the epithelial layer in response to the mapped epithelial profile as described above. Pulse sequence  870  can remove the epithelial layer to expose the stromal layer and/or Bowman&#39;s membrane. Subsequent to removal of the epithelial layer, the stromal layer is ablated to a target ablation profile as described above. In some embodiments, the operator is able to interrupt the treatment upon penetration of the epithelial layer based on visual, or other, feedback from corneal epithelial and/or stromal fluorescence. In some embodiments, delay  860  is increased, for example from 50 ms to 200 ms, upon transition from epithelial sequence  870  to stromal sequence  880  to permit the operator to pause the treatment and mechanically remove the epithelial layer. 
       FIG. 8F  is a simplified schematic illustration of an interleaved treatment table  822  that comprises epithelial sequence  870  interleaved with stromal sequence  880 , according to embodiments of the present invention. Epithelial sequence  870  is interleaved with stromal sequence  880 . Many pulses from stromal sequence  880  are placed at intervals among pulses from epithelial sequence  870  such that pulses from stromal sequence  880  are interspersed among pulses from epithelial sequence  870 . Many of the pulses from stromal sequence  880  that are interspersed among epithelial pulses  870  are located near the beginning portion of the table such that pulses from stromal sequence  880  ablate the epithelial layer. Many pulses from epithelial sequence  870  are placed at intervals among pulses from stromal sequence  880  and located near the end portion of the table, such that pulses from epithelial sequence  870  are interspersed among stromal pulses so as ablate the stromal layer. The laser beam expands from small 2 mm diameter to larger 4 mm diameter eight times during the treatment. 
     One will appreciate that the embodiments shown in  FIGS. 8A to 8F  are merely examples of patterns, sequences, sorting techniques and treatment tables. Additional embodiments will be readily apparent to one or ordinary skill who will recognize variations, alternatives and modifications. For example, wide area pulses may be used to remove most of the epithelium followed by smaller pulses to remove epithelial and stromal tissue, and that some pulses may remove both epithelial and stromal tissue. 
     In some embodiments, an arrangement of pulses can be determined for Bowman&#39;s membrane, and Bowman&#39;s arrangement of pulses may be located within the treatment table in many ways. For example, the pulses that correspond to Bowman&#39;s membrane can be located in a treatment table at a location between epithelial pulses and stromal pulses. The epithelial pulses may be located near the beginning of the treatment table and stromal pulses located near the end of the treatment such that the location of the pulses in the treatment table corresponds to the tissue actually ablated with each pulse. In some embodiments, the treatment table may be interleaved such that Bowman&#39;s pulses are interspersed among epithelial and stromal pulses at many locations in the treatment table. The Bowman&#39;s pulses may be located near the beginning and near the end of the treatment table at locations in the treatment table that correspond to ablation of epithelial tissue and ablation of stromal tissue, respectively. 
       FIG. 9  is a flow chart that schematically illustrates a method  900  of ablating the eye, according to embodiments of the present invention. Method  900  includes a step  910  to map refractive optical properties of the eye. The refractive optical properties of the eye can be mapped in many ways; for example, with a wavefront system that measures the optical properties of the entire path of the eye. A step  915  maps thickness of the epithelial layer. The thickness of the epithelial layer can be mapped in many ways; for example, with an ultrasound machine. A step  920  maps corneal topography of the eye. The corneal topography of the eye of the eye can be mapped in many ways, as described above. A step  925  determines epithelial contribution to the refractive error map of the eye. The epithelial contribution of the refractive map of the eye can be determined from the thickness of the epithelial layer. A step  930  determines the remainder of contribution to the refractive map. The remainder of contribution can be determined by subtracting the epithelial contribution from the map of optical properties of the eye. A step  935  determines the healed profile of the epithelial layer. The healed profile of the epithelial layer can be determined in response to the ablation profile and/or a desired optical correction of the eye to correct optical properties of the eye. A step  945  determines stromal layer ablation profile map. The stromal layer ablation profile map can be determined from the healed profile of the epithelial layer and the remainder of contribution to the refractive map. A step  950  determines a Bowman&#39;s layer ablation profile. A step  955  determines an arrangement of laser beam pulses to ablate the epithelial layer. Step  955  uses epithelial basis data as described above. A step  960  determines an arrangement of laser pulses to ablate the stromal layer. Step  960  uses stromal basis data as described above. A step  965  determines an arrangement of pulses to ablate Bowman&#39;s layer to the profile determined in step  950 . Step  965  uses Bowman&#39;s basis data as described above. A step  970  sorts the laser beam pulses. The pulses can be sorted in inany ways, for example based on diameter of the pulse so that several small pulses are ablated before several large pulses, and several large pulses are ablated before several small pulses several times during the treatment. A step  975  ablates the cornea. The cornea is ablated with the stromal arrangement of the laser beam pulses and the epithelial arrangement of laser beam pulses, as described above. 
     It should be appreciated that the specific steps illustrated in  FIG. 9  provide a particular method of ablating the eye, according to an embodiment of the present invention. Other sequences of steps may also be performed according to alternative embodiments. For example, alternative embodiments of the present invention may perform the steps outlined above in a different order. Moreover, the individual steps illustrated in  FIG. 9  may include multiple sub-steps that may be performed in various sequences as appropriate to the individual step. Furthermore, additional steps may be added or removed depending on the particular applications. In some embodiments, some, all, or none of steps  910 - 950  are performed. For instance, the method  900  need not include steps to measure the eye, such as step  910 , step  915 , or step  920 , as those measurements may have been taken earlier or may not be needed. As another example, determinations related to contributions to the refractive map (steps  925  and  930 ) need not be performed as such determinations may either be unnecessary or may have been previously performed). Determination of the healed profile and of the various other profiles also do not need to be performed as that information may be unnecessary or may have been previously determined. It should be understood that although corneal ablation is described as being based on data related to specific types of corneal tissue (e.g., epithelial, Bowman&#39;s, and stromal), the ablation may be based on data for other types of tissue, such as scar tissue. Thus in an alternative, the method  900  may include receiving and/or determining scar tissue locations and geometry, receiving or determining basis data related to the scar tissue, generating laser beam pulses based on the scar tissue, and ablating the cornea based at least in part on the laser beam pulses generated based on the scar tissue. One of ordinary skill in the art would recognize many variations, modifications, and alternatives. 
     Embodiments of the present invention may use epithelial mapping without refractive correction to the stromal layer. For example, in some embodiments, the epithelium may be mapped as described above and epithelial and stromal treatments calculated to ablate haze or other optical irregularities from the cornea. In some embodiments, the epithelium may be ablated without stromal ablation to remove pathologies from the epithelium. 
       FIGS. 10A to 10H  show examples of images of epithelial fluorescence from a patient treatment. The images shown in  FIGS. 10A to 10H  can be sampled from a treatment, for example a treatment of 1600 pulses. To obtain the images, a UV sensitive CCD camera can be mounted on the side of the microscope beam splitter and used to image the fluorescing event of each pulse, as described above. The camera may have its own frame-capture card located in the system controller computer. A “fire laser” signal, for example TTL (5 volt) signal, can be sent to the camera to trigger frame capture with each pulse, as described above. The exposure of the image may be timed such that the entire fluorescing event will be captured. The exposure time may be limited to 100 μs to avoid capturing unwanted light, including reflections from the patient illumination and room lighting. 
       FIG. 10A  shows a baseline image acquired when the laser is not fired and there is no epithelial fluorescence.  FIG. 10B  shows epithelial fluorescence with a first pulse at a first location, in which fluorescence extends across the first pulse location with an intensity above a threshold value.  FIG. 10C  shows epithelial fluorescence with a second pulse at a second location, in which fluorescence extends across the second pulse location with an intensity above the threshold value.  FIG. 10D  shows epithelial fluorescence with a third pulse at a third location, in which fluorescence extends across the third pulse location with an intensity above the threshold value.  FIG. 10E  shows epithelial fluorescence with a fourth pulse at a fourth location, in which fluorescence extends across the fourth pulse location with an intensity above the threshold value.  FIG. 10F  shows epithelial fluorescence with a fifth pulse at a fifth location, in which fluorescence extends across a majority of the area of the fifth pulse location with an intensity above the threshold value, and portions of the fifth pulse location comprise fluorescence intensity below the threshold value so as to indicate penetration of the epithelium.  FIG. 10G  shows epithelial fluorescence with a sixth pulse at a sixth location, in which fluorescence extends across a minority of the area of the sixth pulse location with an intensity above the threshold value, and portions of the sixth pulse location comprise fluorescence intensity below the threshold value so as to indicate penetration of the epithelium.  FIG. 10H  shows epithelial fluorescence with a seventh pulse at a seventh location, in which fluorescence extends across a minority of the area of the seventh pulse location with an intensity above the threshold value, and portions of the seventh pulse location comprise fluorescence intensity below the threshold value so as to indicate penetration of the epithelium. 
     The images shown in  10 A to  10 H comprise images sampled from a portion of the treatment, and similar images can be acquired from each pulse of the laser treatment for the entire treatment, for example with the camera triggered off the laser and coupled to the frame grabber and shown on the display as described above. The image from each pulse can be shown on the display in real time, such operator is able to visualize penetration of the epithelium with minimal interference from visible light, for example as shown in  FIG. 10A  which shows little interference from visible light at baseline. 
     Plotting General Intensity of Epithelial Fluorescence 
       FIG. 11  shows a plot of image intensity for epithelium removal with images as in  FIGS. 10A to 10H . This plot illustrates characteristics of the fluorescence images obtained with the above described system that can be used to detect penetration and/or clearance of the epithelium. Penetration/breakthrough of the epithelium can encompass at least some portion of the treatment area over which the epithelium which has been completely removed. Clearance of the epithelium may encompass removal of the epithelium over a majority of the surface area of the area targeted for removal. In many embodiments, penetration/breakthrough corresponds to a first amount of fluorescence and epithelial clearance corresponds to a second amount of fluorescence, the second amount smaller than the first amount. 
     The mean intensity value of a 20 pulse rolling average can be graphed to show intensity drop with penetration and/or epi clearance. Each laser beam pulse applied to the epithelium will fluoresce a certain threshold amount. Although the stroma may fluoresce, this amount can be substantially below the threshold amount. The amount of epithelial fluorescence can be quantified by summing the brightness value of each image for an empirical number of patients, for example 20 patients. As each pulse is applied, a specific image intensity can be expected because the exact area of epithelium irradiated is known based on the programmed size of the laser beam. By plotting the fluorescence values for each pulse, for example expected fluorescence minus measured, on a simple line graph inflexion points can signify breakthrough/penetration and clearance areas where epithelium has been removed. A running average of fluorescence values for a plurality of pulses may be used to determine penetration and/or clearance of the epithelium, for example a running average of 20 pulses. Therefore, a signal indicating epithelial penetration and/or clearance can be generated in response to at least one laser beam size, a mean expected fluorescence value, or running average of fluorescence. The signal may comprise a first signal to indicate penetration of the epithelium and a second signal to indicate clearance of the epithelium. 
     Epithelial Layer Pulse Repetition Rate Induction Signal 
       FIG. 12  is a simplified schematic illustration of a sequential treatment table  1200  that comprises epithelial sequence  1270  combined with stromal sequence  1280 , according to embodiments of the present invention. According to some embodiments, epithelial sequence  1270  is located before stromal sequence  1280  such that epithelial sequence  1270  ablates the epithelial layer in response to the mapped epithelial profile as described elsewhere herein. In some cases, the epithelial layer can be ablated based on an estimated epithelial profile or an estimated epithelial thickness. For example, an epithelial profile or epithelial thickness can be estimated based on a patient&#39;s age, a patient&#39;s gender, or other patient factors. In some cases, an epithelial profile or epithelial thickness can be estimated based on a patient&#39;s surgical history (e.g. vision or eye treatments previously administered to the patient), a patient&#39;s medical condition or diagnosis (e.g. keratoconus or diabetes), and the like. Pulse sequence  1270  can remove the epithelial layer to expose the stromal layer and/or Bowman&#39;s membrane. Subsequent to removal of the epithelial layer, the stromal layer can be ablated to a target ablation profile as described elsewhere herein. 
     As shown here, the epithelial sequence  1270  can include a first epithelial arrangement of laser beam pulses  1270   a  and a second epithelial arrangement of laser beam pulses  1270   b . According to some embodiments, the first epithelial arrangement of laser beam pulses  1270   a  can terminate in response to a crossover signal  1275 . According to some embodiments, the second epithelial arrangement of laser beam pulses  1270   b  can initiate in response to the crossover signal  1275 . In some cases, the first epithelial arrangement of laser beam pulses  1270   a  can terminate and the second epithelial arrangement of laser beam pulses  1270   b  can initiate in response to the crossover signal  1275 . The crossover signal  1275  is some signal that marks the boundary between the first epithelial arrangement of laser beam pulses  1270   a  and the second epithelial arrangement of laser beam pulses  1270   b . In some embodiments, the crossover signal  1275  is generated when the first epithelial arrangement of laser beam pulses  1270   a  is complete and acts as a trigger to begin the second epithelial arrangement of laser beam pulses  1270   b . More specifically, in such embodiments, the first epithelial arrangement of laser beam pulses  1270   a  comprises a pre-planned set of pulses generated in response to corneal data. The crossover signal  1275  may be generated when that set of pulses is fully complete. In some instances, the first epithelial arrangement of laser beam pulses  1270   a  is interrupted. The first epithelial arrangement of laser beam pulses  1270   a  may be interrupted upon automatic detection of a crossover event, which is an event detected by the laser system  10  based on processing by a processing system of the laser system  10 . In such instances, the crossover event represents a particular event in the process of epithelial ablation that is associated with crossover into ablation of the epithelium via the second epithelial arrangement of laser beam pulses  1270   b . This event may occur when the laser system  10  determines that one of the following has occurred: automated detection that the epithelial layer has been removed, automated detection that a particular portion or amount of the epithelial layer remains, or automated detection that a breakthrough in the epithelial layer has occurred. Exemplary automated detection features (e.g. for epithelial penetration and/or clearance) are describe in U.S. Pat. No. 8,926,600, the content of which is incorporated herein by reference. If the crossover signal  1275  is generated within the laser system  10  based on automatic detection that some condition is satisfied, then the crossover signal  1275  is received and processed internally within the laser system  10 . In an alternative, the crossover signal  1275  is generated in response to sensing an input from a human operator or other operator external to the laser system  10 . In an example, an operator is observing the display as described with respect to  FIGS. 10A-10H  and determines that the first epithelial arrangement of laser beam pulses  1270   a  should end. In response, to receiving the crossover signal  1275  (whether generated automatically or in response to manual input from an operator), the laser system  10  triggers a transition to the second epithelial arrangement of laser beam pulses  1270   b.    
     The first epithelial arrangement of laser beam pulses  1270   a  can have a first number of individual laser pulses. The second epithelial arrangement of laser beam pulses  1270   b  can have a second number of individual laser pulses. According to some embodiments, the second epithelial arrangement of laser beam pulses  1270   b  has a number of laser pulses within a range from 50 pulses to 250 pulses. In some instances, delivery of the second epithelial arrangement of laser beam pulses  1270   b  is sufficient to ensure that no epithelial layer remains at the targeted region (or that a sufficiently small amount of epithelial layer remains). In some instances, delivery of the second epithelial arrangement of laser beam pulses  1270   b  does not result in complete removal of the epithelial layer the targeted region. In some instances, a physician or operator may opt to terminate delivery of the second epithelial arrangement of laser beam pulses  1270   b , for example prior to completion of the entire sequence of the second epithelial arrangement of laser beam pulses  1270   b.    
     In some instances, the first epithelial arrangement of laser beam pulses  1270   a  includes a first individual laser pulse having a first epithelial basis data. In some instances, the second epithelial arrangement of laser beam pulses  1270   b  includes a second individual laser pulse having a second epithelial basis data. According to some embodiments, the first epithelial basis data is the same as the second epithelial basis data. 
     The first epithelial arrangement of laser beam pulses  1270   a  can have a first epithelial pulse repetition rate. The second epithelial arrangement of laser beam pulses  1270   b  can have a second epithelial pulse repetition rate. The first epithelial pulse repetition rate can be different (e.g. faster or slower) than the second epithelial pulse repetition rate. In some cases, the first epithelial pulse repetition rate is within a range from 18 Hz to 22 Hz. In some cases, the first epithelial pulse repetition rate is within a range from 10 Hz to 1000 Hz. In some cases, the second epithelial pulse repetition rate is within a range from 5 Hz to 6 Hz. In some cases, the second epithelial pulse repetition rate is within a range from 5 Hz to 10 Hz. According to some embodiments, the first epithelial arrangement of laser beam pulses  1270   a  is delivered at a pulse repetition rate that is higher than the pulse repetition rate of the second epithelial arrangement of laser beam pulses  1270   b , and the slower pulse repetition rate of the second epithelial arrangement of laser beam pulses  1270   b  can make it easier for the physician or operator to monitor or terminate delivery of the second epithelial arrangement of laser beam pulses  1270   b . For example, the physician or operator may decide to stop or pause the ablation treatment during delivery of the second epithelial arrangement of laser beam pulses  1270   b  when a desired amount of epithelial tissue has been removed, or when a certain percentage of breakthrough is achieved or observed. In some cases, the first epithelial arrangement of laser beam pulses  1270   a  and/or the second epithelial arrangement of laser beam pulses  1270   b  are based on a predetermined calculation or factor. For example, the induction signal can be based on one or more of a patient&#39;s age, patient&#39;s gender and/or another factor. 
     According to some embodiments, the stromal sequence  1280  can include a stromal arrangement of laser beam pulses. In some instances, the stromal arrangement of laser beam pulses can be delivered at a stromal pulse repetition rate. In some cases, the stromal pulse repetition rate can be a variable repetition rate. In some cases, the variable repetition rate can have a maximum rate of 20 Hz. In some cases, the variable repetition rate can have a maximum rate of 50 Hz. In some cases, the variable repetition rate can have a maximum rate of 1000 Hz. The stromal arrangement can include one or more individual laser pulses having a stromal basis data. In some cases, the stromal pulse repetition rate is independent of the first epithelial pulse repetition rate. In some cases, the stromal pulse repetition rate is independent of the second epithelial pulse repetition rate. In some cases, the stromal pulse repetition rate is independent of the first epithelial pulse repetition rate and the second epithelial pulse repetition rate. 
     Individual laser pulses of a pulse arrangement or sets of laser pulses of a pulse arrangement can have a pulse diameter  1230 , an x-coordinate  1240 , a y-coordinate  1250 , and a delay  1260 . A number of pulses  1210  for each diameter and/or pulse number can also be specified for each pulse of the arrangement. A treatment table with delays, positions and diameters sorted to avoid tissue heating is described, for example, in U.S. Pat. No. 7,077,838, the contents of which are incorporated herein by reference. In some cases, embodiments of the present invention may include aspects of treatment tables and/or basis data such as that described in US Patent Publication No. 2014/0135748, the contents of which are incorporated herein by reference. An illustrative epithelial treatment for epithelial mapping treatments may include 80 pulses of 1 mm diameter, 80 pulses of 2 mm diameter, 80 pulses of 3 mm diameter, and 80 pulses of 4 mm diameter. 
     According to some embodiments, some of all of the epithelial sequence  1270  can be performed in a scanning manner. For example, the epithelial arrangement of laser beam pulses can include a first laser beam pulse centered at a first position on the eye and a second laser beam pulse centered at a second position on the eye, such that the first position is different from the second position. Relatedly, individual pulses of the epithelial sequence  1270  can be centered on any desired location relative to the center of the eye or cornea. In some instances, one or more of the individual pulses of the epithelial sequence  1270  can be offset from the center of the eye (or cornea, pupil, or some other feature of the eye). In some instances, a treatment may include scanning laser pulses so they are centered on a variety of different locations relative to the center of the eye (or cornea, pupil, or some other feature of the eye). 
     Embodiments of the present invention encompass automated or computer implemented methods for treating a patient eye based on the techniques described in conjunction with  FIG. 12 . 
     For example, exemplary methods may involve treating a region of a cornea of an eye using a laser. The region of the cornea can include an epithelial layer disposed over a stromal layer. As depicted in  FIG. 13 , aspects of such a treatment method  1300  may include receiving, at a processor system  1310 , an epithelial thickness map of the eye  1320 . In some cases, instead of a thickness map, the processor system can receive an estimated thickness of the epithelium. Method  1300  can also include receiving, at the processor system  1310 , a crossover signal  1330 , which, in some embodiments, is the same as the crossover signal  1275 . As with crossover signal  1275  described with respect to  FIG. 12 , the crossover signal  1330  can be generated either by an operator  1395  monitoring progress of the treatment via a camera  1390  and/or other device, or can be generated by code  1360  in response to an automatic determination, based on input from the camera  1390  and/or other device. Further, method  1300  can include receiving, at the processor system  1310 , an epithelial basis data  1340  corresponding to an epithelial laser pulse ablation profile. Method  1300  can also include receiving, at the processor system  1310 , a stromal basis data  1350  corresponding to a stromal laser pulse ablation profile. Still further, method  1300  can include executing, using the processor system, computer executable code  1360 . The code  1360  can be stored on a non-transitory computer readable medium, and the code  1360  can include instructions for a laser  1370  to ablate a patient eye  1380 . For example, the code  1360  can include instructions for the laser  1370  to ablate the epithelial layer with a first epithelial arrangement of laser beam pulses at a first epithelial pulse repetition rate and a second epithelial arrangement of laser beam pulses at a second epithelial pulse repetition rate, where the first epithelial arrangement of laser beam pulses includes a first individual laser pulse corresponding to the epithelial basis data and the second epithelial arrangement of laser beam pulses includes a second individual laser pulse corresponding to the epithelial basis data. Further, the code  1360  can include instructions for the laser  1370  to ablate the stromal layer with a stromal arrangement of laser beam pulses at a stromal pulse repetition rate. The stromal arrangement can include a third individual laser pulse corresponding to the stromal basis data. The instructions can be based on the epithelial thickness map of the eye and the crossover signal. Delivery of the epithelial and stromal laser beam pulse arrangements can constitute a treatment of the eye of the patient using the laser  1370 . 
     Partial Laser Epithelial Removal 
       FIG. 14  is a simplified schematic illustration of a sequential treatment table  1400  that comprises an epithelial treatment aspect  1470  combined with a stromal treatment aspect  1480 , according to embodiments of the present invention. According to some embodiments, epithelial aspect  1470  is located before stromal aspect  1480  such that epithelial aspect  1470  is first administered to the epithelial layer followed by administration of the stromal aspect  1480  to the stromal layer. In some cases, the epithelial layer can be ablated or treated at least partially based on an epithelial thickness parameter. In some cases, an epithelial thickness parameter can be an estimated epithelial profile or an estimated epithelial thickness. For example, an epithelial profile or epithelial thickness can be estimated based on a patient&#39;s age, a patient&#39;s gender, or other patient factors. In some cases, an epithelial profile or epithelial thickness can be estimated based on a patient&#39;s surgical history (e.g. vision or eye treatments previously administered to the patient), a patient&#39;s medical condition or diagnosis (e.g. keratoconus or diabetes), and the like. In some cases, an epithelial thickness parameter can be an epithelial thickness map. Epithelial treatment aspect  1470  can remove the epithelial layer to expose the stromal layer and/or Bowman&#39;s membrane. Subsequent to removal of the epithelial layer, the stromal layer can be ablated to a target ablation profile as described elsewhere herein. 
     As shown here, the epithelial treatment aspect  1470  can include an epithelial arrangement of laser beam pulses  1470   a  and a manual epithelial removal protocol  1470   b . According to some embodiments, the first epithelial arrangement of laser beam pulses  1470   a  can terminate based on a value that represents a percentage of epithelial tissue designated for removal (also referred to as an “epithelial percentage value”). For example, the epithelial layer can have a thickness (e.g. estimated or measured), and the percentage of epithelial tissue can correspond to a percentage of the thickness of the epithelial layer. In some cases, the percentage is within a range from 50 percent to 95 percent. In some instances, a treatment system can include an input that receives the percentage indicator from the operator or physician. For example, the operator or physician can designate that the epithelial arrangement of laser beam pulses  1470   a  be effective to remove 50 percent of the thickness of the epithelial layer. As another example, the physician can program the treatment system with a percentage indicator of 95 percent, such that the epithelial arrangement of laser beam pulses  1470   a  is effective to remove 95 percent of the thickness of the epithelial layer. In this way, the physician or operator can provide instructions to the treatment system that result in automated laser removal of any desired percentage or amount of the epithelial layer. Laser ablation of the epithelial layer can terminate at stage  1475 , after which the treatment can include manual removal of epithelial tissue at step  1470   b , followed by administration of the stromal treatment aspect  1480 . In some instances, manual removal of the epithelium can be performed using a brush, a scraping tool such as a scapula, or a debridement instrument. In some instances, manual removal may also involve a chemical treatment. For example, alcohol can be applied to the epithelial tissue, and following the alcohol treatment or saturation, debridement or other manual techniques can be used to remove the epithelial tissue. According to some embodiments, the system can provide a visual or audible prompt to an operator to proceed with the manual removal protocol  1470   b , following completion of an epithelial arrangement of laser beam pulses  1470   a.    
     The epithelial arrangement of laser beam pulses  1470   a  can have a number of individual laser pulses. In some instances, the epithelial arrangement of laser beam pulses  1470   a  includes an individual laser pulse having an epithelial basis data. The epithelial arrangement of laser beam pulses  1470   a  can have an epithelial pulse repetition rate. In some cases, the epithelial pulse repetition rate is within a range from 18 Hz to 22 Hz. In some cases, the epithelial pulse repetition rate is within a range from 10 Hz to 1000 Hz. 
     According to some embodiments, the stromal treatment aspect  1480  can include a stromal arrangement of laser beam pulses. In some instances, the stromal arrangement of laser beam pulses can be delivered at a stromal pulse repetition rate. In some cases, the stromal pulse repetition rate can be a variable repetition rate. In some cases, the variable repetition rate can have a maximum rate of 20 Hz. In some cases, the variable repetition rate can have a maximum rate of 50 Hz. In some cases, the variable repetition rate can have a maximum rate of 1000 Hz. The stromal arrangement can include one or more individual laser pulses having a stromal basis data. 
     Individual laser pulses of a pulse arrangement or sets of laser pulses of a pulse arrangement can have a pulse diameter  1430 , an x-coordinate  1440 , a y-coordinate  1450 , and a delay  1460 . A number of pulses  1410  for each diameter and/or pulse number can also be specified for each pulse of the arrangement. A treatment table with delays, positions and diameters sorted to avoid tissue heating is described, for example, in U.S. Pat. No. 7,077,838, the contents of which are incorporated herein by reference. In some cases, embodiments of the present invention may include aspects of treatment tables and/or basis data such as that described in US Publication No. 2014/0135748, the contents of which are incorporated herein by reference. 
     According to some embodiments, some of all of the epithelial arrangement of laser beam pulses  1470   a  can be performed in a scanning manner. For example, the epithelial arrangement of laser beam pulses can include a first laser beam pulse centered at a first position on the eye and a second laser beam pulse centered at a second position on the eye, such that the first position is different from the second position. Relatedly, individual pulses of the epithelial arrangement of laser beam pulses  1470   a  can be centered on any desired location relative to the center of the eye or cornea. In some instances, one or more of the individual pulses of the epithelial arrangement of laser beam pulses  1470   a  can be offset from the center of the eye (or cornea, pupil, or some other feature of the eye). In some instances, a treatment may include scanning laser pulses so they are centered a variety of different locations relative to the center of the eye (or cornea, pupil, or some other feature of the eye). 
     Embodiments of the present invention encompass automated or computer implemented methods for treating a patient eye based on the techniques described in conjunction with  FIG. 14 . For example, exemplary methods may involve treating a region of a cornea of an eye using a laser. The region of the cornea can include an epithelial layer disposed over a stromal layer. As depicted in  FIG. 15 , aspects of such a treatment method  1500  may include receiving, at a processor system  1510 , an epithelial thickness parameter  1520  associated with the eye  1580 . In some cases, a thickness parameter can be a thickness map. In some cases, a thickness parameter can be an estimated thickness of the epithelium. Method  1500  can also include receiving, at the processor system  1510 , an epithelial basis data  1540  corresponding to an epithelial laser pulse ablation profile. Method  1500  can also include receiving, at the processor system  1510 , a stromal basis data  1550  corresponding to a stromal laser pulse ablation profile. Still further, method  1500  can include executing, using the processor system, computer executable code  1560 . The code  1560  can be stored on a non-transitory computer readable medium, and the code  1560  can include instructions for a laser  1570  to ablate a patient eye  1580 . For example, the code  1560  can include instructions for the laser  1570  to ablate the epithelial layer with an epithelial arrangement of laser beam pulses. The epithelial arrangement of laser beam pulses can include at least one individual laser pulse corresponding to the epithelial basis data. The epithelial arrangement of laser pulses can be effective to remove the designated percentage of epithelial tissue. The instructions can be based on the epithelial thickness map of the eye and the operator input. Further, the code  1560  can include instructions for the laser  1570  to ablate the stromal layer with a stromal arrangement of laser beam pulses at a stromal pulse repetition rate. The stromal arrangement can include at least one individual laser pulse corresponding to the stromal basis data. Delivery of the epithelial and stromal laser beam pulse arrangements via laser  1570 , along with the manual removal of epithelial tissue  1530 , can constitute a treatment of the eye of the patient. 
     Uniform Stromal Ablation Following Epithelial Ablation 
       FIG. 16  is a simplified schematic illustration of a sequential treatment table  1600  that comprises epithelial sequence  1670  combined with stromal sequence  1680 , according to embodiments of the present invention. According to some embodiments, epithelial sequence  1670  is located before stromal sequence  1680  such that epithelial sequence  1670  ablates the epithelial layer in response to the mapped epithelial profile as described elsewhere herein. In some cases, the epithelial layer can be ablated based on an estimated epithelial profile or an estimated epithelial thickness. For example, an epithelial profile or epithelial thickness can be estimated based on a patient&#39;s age, a patient&#39;s gender, or other patient factors. In some cases, an epithelial profile or epithelial thickness can be estimated based on a patient&#39;s surgical history (e.g. vision or eye treatments previously administered to the patient), a patient&#39;s medical condition or diagnosis (e.g. keratoconus or diabetes), and the like. Pulse sequence  1670  can remove the epithelial layer to expose the stromal layer and/or Bowman&#39;s membrane. Subsequent to removal of the epithelial layer, the stromal layer can be ablated. 
     In some cases, the epithelial sequence  1670  can include at least one individual laser pulse corresponding to epithelial basis data. In some cases, the epithelial arrangement of laser beam pulses is based on an epithelial thickness map. The first epithelial arrangement of laser beam pulses  1670  can have a first epithelial pulse repetition rate. In some cases, the epithelial pulse repetition rate is within a range from 5 Hz to 1000 Hz. 
     As depicted in  FIG. 16 , stromal sequence  1680  includes a first stromal arrangement of laser beam pulses  1680   a  and a second stromal arrangement of laser beam pulse  1680   b . In some instances, the anterior portion of the patient stromal tissue may be irregular or lack a uniform or smooth surface shape. In these and other situation, a physician or operator may desire to remove the irregular anterior stromal features, so as to provide an anterior stromal surface that is smooth or uniform. In some instances, a patient may have received a previous vision treatment procedure, for example which may have resulted in an irregular or non-uniform stromal surface shape, and the instant vision treatment procedure is performed subsequent to that previous procedure so as to produce a regular or uniform posterior stromal surface. Administration of the first stromal arrangement of laser beam pulses  1680   a  can be effective in accomplishing these objectives. Once the desired smooth or uniform anterior stromal surface is obtained (e.g. as indicated by stage  1685 ), the second stromal arrangement of laser beam pulse  1680   b  can be administered. According to some embodiments, the second stromal arrangement of laser beam pulse  1680   b  is configured to produce a desired refractive optical property in the eye (e.g. to treat myopia, hyperopia, astigmatism, presbyopia, or some other vision condition). Hence, treatment embodiments can include ablating the stromal layer with a first stromal arrangement of laser beam pulses, where the first stromal arrangement of laser beam pulses includes at least one individual laser pulse corresponding to the epithelial basis data, and where the first stromal arrangement of laser beam pulses effective to remove a layer of stromal tissue so as to produce a smooth or uniform anterior stromal surface shape. In some instances, the first stromal arrangement of laser beam pulses is effective to remove or reduce a scar present on the stromal layer of the cornea. 
     Further, treatment embodiments can include additional ablation of the stromal layer with a second stromal arrangement of laser beam pulses. The second stromal arrangement of laser beam pulses can include at least one individual laser pulse corresponding to the stromal basis data. The second stromal arrangement of laser beam pulses can be based on a refractive optical property of the eye (e.g. low order aberration, high order aberration, or a combination thereof). 
     According to some embodiments, the stromal sequence  1680  can include a stromal arrangement of laser beam pulses. In some instances, the stromal arrangement of laser beam pulses can be delivered at a stromal pulse repetition rate. In some cases, the stromal pulse repetition rate can be a variable repetition rate. In some cases, the variable repetition rate can have a maximum rate of 20 Hz. In some cases, the variable repetition rate can have a maximum rate of 50 Hz. In some cases, the variable repetition rate can have a maximum rate of 1000 Hz. The stromal arrangement can include one or more individual laser pulses having a stromal basis data. In some cases, the first stromal arrangement of laser beam pulses  1680   a  can be delivered at an epithelial pulse repetition rate (e.g. within a range from 5 Hz to 1000 Hz) and the second stromal arrangement of laser beam pulse  1680   b  can be delivered at a stromal pulse repetition rate. 
     Individual laser pulses of a pulse arrangement or sets of laser pulses of a pulse arrangement can have a pulse diameter  1630 , an x-coordinate  1640 , a y-coordinate  1250 , and a delay  1260 . A number of pulses  1210  for each diameter and/or pulse number can also be specified for each pulse of the arrangement. A treatment table with delays, positions and diameters sorted to avoid tissue heating is described, for example, in U.S. Pat. No. 7,077,838, the contents of which are incorporated herein by reference. In some cases, embodiments of the present invention may include aspects of treatment tables and/or basis data such as that described in US Publication No. 2014/0135748, the contents of which are incorporated herein by reference. An illustrative epithelial treatment for epithelial mapping treatments may include 80 pulses of 1 mm diameter, 80 pulses of 2 mm diameter, 80 pulses of 3 mm diameter, and 80 pulses of 4 mm diameter. 
     According to some embodiments, some of all of the epithelial sequence  1670  can be performed in a scanning manner. For example, the epithelial arrangement of laser beam pulses can include a first laser beam pulse centered at a first position on the eye and a second laser beam pulse centered at a second position on the eye, such that the first position is different from the second position. Relatedly, individual pulses of the epithelial sequence  1670  can be centered on any desired location relative to the center of the eye or cornea. In some instances, one or more of the individual pulses of the epithelial sequence  1670  can be offset from the center of the eye (or cornea, pupil, or some other feature of the eye). In some instances, a treatment may include scanning laser pulses so they are centered a variety of different locations relative to the center of the eye (or cornea, pupil, or some other feature of the eye). 
     Although the first stromal arrangement of laser beam pulses  1680   a  is referred to as a stromal arrangement, it is understood that this arrangement of pulses can administered to portions of tissue that are a combination of both epithelial and stromal tissue. For example, as depicted in  FIG. 16 , the epithelial arrangement of laser beam pulses  1670  can be administered to remove an upper layer of tissue that is all or mostly epithelial tissue, the first stromal arrangement of laser beam pulses  1680   a  can be administered to remove a middle layer of tissue that is a combination of epithelial and stromal tissue, and the second stromal arrangement of laser beam pulse  1680   b  can be administered to remove a lower layer of tissue that is all or mostly stromal tissue. In some cases, the epithelial arrangement of laser beam pulses  1670  (and optionally, the first stromal arrangement of laser beam pulses  1680   a ) can include a generic or standard arrangement of pulses that can be delivered to any patient or a population of patients regardless of their vision condition. In some cases, the second stromal arrangement of laser beam pulse  1680   b  can include an arrangement of pulses that is specific or unique to a particular patient. 
     In some cases, the physician or operator can visually inspect the tissue fluorescence so as to monitor the progress of the first stromal arrangement of laser beam pulses  1680   a . As depicted in  FIG. 16A , the anterior surface of the stromal layer can have wrinkles, undulations, or other imperfections. As delivery of the first stromal arrangement of laser beam pulses  1680   a  progresses, various patterns of fluorescence may be visible as a results of such undulations or surface irregularities (which often are about 1 to 2 microns in depth). As such, the physician or operator will be able to visually observe artifact patterns, visual irregularities, undulating patterns, and other irregular fluorescence patterns. The disappearance of the fluorescence or fluorescence pattern can indicate that the epithelium has been removed. Hence, in order to achieve a smooth or uniform anterior stromal surface, the physician or operator can continue delivering the first stromal arrangement of laser beam pulses  1680   a  until the fluorescence pattern disappears and there is no longer any visible fluorescence. In some cases, the first stromal arrangement of laser beam pulses  1680   a  is not intended to induce any particular refractive or corrective shape on the stroma. A primary purpose of the first stromal arrangement of laser beam pulses  1680   a  can be to ablate through a portion of stroma while removing residual epithelium to smooth out localized imperfections, undulations, or wrinkles which may be masked by epithelial smoothing. As described elsewhere herein, such imperfections may be exposed only after ablating through a portion of the epithelium. In some cases, delivery of epithelial and/or stromal pulses can be controlled or modulated (e.g. interrupted) in response to a presence or absence of tissue fluorescence of at least one of the epithelial layer, a Bowman&#39;s membrane, or the stromal layer. 
     In another example, as depicted in  FIG. 16B , the first epithelial arrangement of laser beam pulses  1670  can be administered to remove an upper layer of tissue that is all or mostly epithelial tissue, the first stromal arrangement of laser beam pulses  1680   a  can be administered to remove a middle layer of tissue that is a combination of epithelial and stromal tissue. As shown here, pulses  1680   a  extend further into the stromal layer as compared to  FIG. 16A , specifically by an amount C. For example, during delivery of the first stromal arrangement of laser beam pulses  1680   a , the physician or operator may continue the first stromal arrangement even after it appears that all epithelium has been removed. In some cases, the amount C corresponds to an additional depth having a value within a range from 1 micron to 5 microns. Subsequently, the second stromal arrangement of laser beam pulse  1680   b  can be administered to remove a lower layer of tissue that is all or mostly stromal tissue. 
     As depicted in  FIG. 16C , an epithelial sequence  1670  can be delivered to remove an upper layer of epithelium, and subsequently, epithelial tissue that remains between or near the stromal undulations can be removed manually. 
     Embodiments of the present invention encompass automated or computer implemented methods for treating a patient eye based on the techniques described in conjunction with  FIG. 16 . For example, exemplary methods may involve treating a region of a cornea of an eye using a laser. The region of the cornea can include an epithelial layer disposed over a stromal layer. As depicted in  FIG. 17 , aspects of such a treatment method  1700  may include receiving, at a processor system  1710 , an epithelial thickness map of the eye  1720 . In some cases, instead of a thickness map, the processor system can receive an estimated thickness of the epithelium. Method  1700  can also include receiving, at the processor system  1710 , a refractive optical property of the eye  1730 . Further, method  1700  can include receiving, at the processor system  1710 , an epithelial basis data  1740  corresponding to an epithelial laser pulse ablation profile. Method  1700  can also include receiving, at the processor system  1710 , a stromal basis data  1750  corresponding to a stromal laser pulse ablation profile. Still further, method  1700  can include executing, using the processor system, computer executable code  1760 . 
     The code  1760  can be stored on a non-transitory computer readable medium, and the code  1760  can include instructions for a laser  1770  to ablate a patient eye  1780 . For example, the code  1760  can include instructions for the laser  1770  to ablate the epithelial layer of the eye  1780  with an epithelial arrangement of laser beam pulses, where the epithelial arrangement of laser beam pulses includes one or more individual laser pulses corresponding to the epithelial basis data, and where the epithelial arrangement of laser beam pulses is based on the epithelial thickness map. Further, the code  1760  can include instructions for the laser  1770  to ablate the stromal layer with a first stromal arrangement of laser beam pulses, where the first stromal arrangement of laser beam pulses includes one or more individual laser pulses corresponding to the epithelial basis data, and where the first stromal arrangement of laser beam pulses is effective to remove an amount of stromal tissue so as to produce a uniform anterior stromal surface. Still further, the code  1760  can include instructions for the laser  1770  to ablate the stromal layer with a second stromal arrangement of laser beam pulses, where the second stromal arrangement of laser beam pulses includes one or more individual laser pulses corresponding to the stromal basis data, and where the second stromal arrangement of laser beam pulses is based on the refractive optical property of the eye. In this way, treatment method  1700  can be carried out so as to treat a region of the cornea of the patient eye using a laser, where the region of the cornea includes an epithelial layer disposed over a stromal layer. According to some embodiments, the first stromal arrangement of laser beam pulses is effective to remove a scar present on the stromal layer of the cornea. According to some embodiments, the epithelial arrangement of laser beam pulses includes a first laser beam pulse centered at a first position on the eye and a second laser beam pulse centered at a second position on the eye, where the first position is different from the second position. Delivery of the epithelial and stromal laser beam pulse arrangements can constitute a treatment of the eye of the patient using the laser  1770 . 
       FIG. 18  is a simplified block diagram of an exemplary computer system  1822  that may be used by a laser surgical system according to embodiments of the present invention. Computer system  1822  typically includes at least one processor  1852  which may communicate with a number of peripheral devices via a bus subsystem  1854 . These peripheral devices may include a storage subsystem  1856 , comprising a memory subsystem  1858  and a file storage subsystem  1860 , user interface input devices  1862 , user interface output devices  1864 , and a network interface subsystem  1866 . Network interface subsystem  1866  provides an interface to outside networks  1868  and/or other devices, such as a laser delivery system and/or or a diagnostic system such as a wavefront measurement system. 
     User interface input devices  1862  may include a keyboard, pointing devices such as a mouse, trackball, touch pad, or graphics tablet, a scanner, foot pedals, a joystick, a touchscreen incorporated into the display, audio input devices such as voice recognition systems, microphones, and other types of input devices. User input devices  1862  will often be used to download a computer executable code from a tangible storage media embodying any of the methods of the present invention. In general, use of the term “input device” is intended to include a variety of conventional and proprietary devices and ways to input information into computer system  1822 . 
     User interface output devices  1864  may include a display subsystem, a printer, a fax machine, or non-visual displays such as audio output devices. The display subsystem may be a cathode ray tube (CRT), a flat-panel device such as a liquid crystal display (LCD), a projection device, or the like. The display subsystem may also provide a non-visual display such as via audio output devices. In general, use of the term “output device” is intended to include a variety of conventional and proprietary devices and ways to output information from computer system  1822  to a user. 
     Storage subsystem  1856  can store the basic programming and data constructs that provide the functionality of the various embodiments of the present invention. For example, a database and modules implementing the functionality of the methods of the present invention, as described herein, may be stored in storage subsystem  1856 . These software modules are generally executed by processor  1852 . In a distributed environment, the software modules may be stored on a plurality of computer systems and executed by processors of the plurality of computer systems. Storage subsystem  1856  typically comprises memory subsystem  58  and file storage subsystem  1860 . 
     Memory subsystem  1858  typically includes a number of memories including a main random access memory (RAM)  1870  for storage of instructions and data during program execution and a read only memory (ROM)  1872  in which fixed instructions are stored. File storage subsystem  1860  provides persistent (non-volatile) storage for program and data files, and may include tangible storage media  29  ( FIG. 1A ) which may optionally embody wavefront sensor data, wavefront gradients, a wavefront elevation map, a treatment map, and/or an ablation table. File storage subsystem  1860  may include a hard disk drive, a floppy disk drive along with associated removable media, a Compact Digital Read Only Memory (CD-ROM) drive, an optical drive, DVD, CD-R, CD-RW, solid-state removable memory, and/or other removable media cartridges or disks. One or more of the drives may be located at remote locations on other connected computers at other sites coupled to computer system  1822 . The modules implementing the functionality of the present invention may be stored by file storage subsystem  1860 . 
     Bus subsystem  1854  provides a mechanism for letting the various components and subsystems of computer system  1822  communicate with each other as intended. The various subsystems and components of computer system  1822  need not be at the same physical location but may be distributed at various locations within a distributed network. Although bus subsystem  1854  is shown schematically as a single bus, alternate embodiments of the bus subsystem may utilize multiple busses. 
     Computer system  1822  itself can be of varying types including a personal computer, a portable computer, a workstation, a computer terminal, a network computer, a control system in a wavefront measurement system or laser surgical system, a mainframe, or any other data processing system. Due to the ever-changing nature of computers and networks, the description of computer system  1822  depicted in  FIG. 18  is intended only as a specific example for purposes of illustrating one embodiment of the present invention. Many other configurations of computer system  1822  are possible having more or less components than the computer system depicted in  FIG. 18 . 
     All patent filings (including patents, patent applications, and patent publications), scientific journals, books, treatises, technical references, and other publications and materials discussed in this application are incorporated herein by reference in their entirety for all purposes. 
     A variety of modifications are possible within the scope of the present invention. A variety of parameters, variables, factors, and the like can be incorporated into the exemplary method steps or system modules. While the specific embodiments have been described in some detail, by way of example and for clarity of understanding, a variety of adaptations, changes, and modifications will be obvious to those of skill in the art. Although the invention has been described with specific reference to a wavefront system using lenslets, other suitable wavefront systems that measure angles of light passing through the eye may be employed. For example, systems using the principles of ray tracing aberrometry, tscherning aberrometry, and dynamic skiascopy may be used with embodiments of the current invention. The above systems are available from TRACEY Technologies of Bellaire, Tex., Wavelight of Erlangen, Germany, and Nidek, Inc. of Fremont, Calif., respectively. Embodiments of the invention may also be practiced with a spatially resolved refractometer as described in U.S. Pat. Nos. 6,099,125; 6,000,800; and 5,258,791, the full disclosures of which are incorporated herein by reference. Treatments that may benefit from the invention include intraocular lenses, contact lenses, spectacles and other surgical methods in addition to refractive laser corneal surgery. 
     All features of the described systems are applicable to the described methods mutatis mutandis, and vice versa. Each of the calculations or operations discussed herein may be performed using a computer or other processor having hardware, software, and/or firmware. The various method steps may be performed by modules, and the modules may comprise any of a wide variety of digital and/or analog data processing hardware and/or software arranged to perform the method steps described herein. The modules optionally comprising data processing hardware adapted to perform one or more of these steps by having appropriate machine programming code associated therewith, the modules for two or more steps (or portions of two or more steps) being integrated into a single processor board or separated into different processor boards in any of a wide variety of integrated and/or distributed processing architectures. These methods and systems will often employ a tangible media embodying machine-readable code with instructions for performing the method steps described above. Suitable tangible media may comprise a memory (including a volatile memory and/or a non-volatile memory), a storage media (such as a magnetic recording on a floppy disk, a hard disk, a tape, or the like; on an optical memory such as a CD, a CD-R/W, a CD-ROM, a DVD, or the like; or any other digital or analog storage media), or the like. While the exemplary embodiments have been described in some detail, by way of example and for clarity of understanding, those of skill in the art will recognize that a variety of modification, adaptations, and changes may be employed. 
     The methods and apparatuses of the present invention may be provided in one or more kits for such use. The kits may comprise a system for determining a treatment for an eye of a patient, and instructions for use. Optionally, such kits may further include any of the other system components described in relation to the present invention and any other materials or items relevant to the present invention. The instructions for use can set forth any of the methods as described herein. 
     While the above provides a full and complete disclosure of exemplary embodiments of the present invention, various modifications, alternate constructions and equivalents may be employed as desired. Consequently, although the embodiments have been described in some detail, by way of example and for clarity of understanding, a variety of modifications, changes, and adaptations will be obvious to those of skill in the art. Accordingly, the above description and illustrations should not be construed as limiting the invention, which can be defined by the claims. 
     Where a range of values is provided, it is understood that each intervening value between the upper and lower limits of that range is also specifically disclosed, to the smallest fraction of the unit or value of the lower limit, unless the context clearly dictates otherwise. Any encompassed range between any stated value or intervening value in a stated range and any other stated or intervening value in that stated range is disclosed. The upper and lower limits of those smaller ranges may independently be included or excluded in the range, and each range where either, neither, or both limits are included in the smaller range is also disclosed and encompassed within the technology, subject to any specifically excluded limit, value, or encompassed range in the stated range. Where the stated range includes one or both of the limits, ranges excluding either or both of those included limits are also included. 
     It is understood that other embodiments may fall within the spirit and scope of the invention. The scope of the invention should, therefore, be determined with reference to the appended claims along with their full scope of equivalents.