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Systems, apparatus, and methods are disclosed for locating tissue layer transitions within a cornea, including focusing a laser to a laser spot with an energy below a photodisruption threshold of the cornea, varying a position of the focal spot of the laser between an anterior surface of the cornea

Systems, apparatus, and methods are disclosed for locating tissue layer transitions within a cornea, including focusing a laser to a laser spot with an energy below a photodisruption threshold of the cornea, varying a position of the focal spot of the laser between an anterior surface of the cornea and a posterior surface of the cornea, and determining one or more transitions of the tissue layers based on a change in harmonic light generated by the laser spot.

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1. A method of locating tissue layers within a cornea, the cornea having an anterior surface, a posterior surface, and a photodisruption threshold, the method comprising the steps of: generating a pulsed laser beam from a femtosecond laser, the laser beam having a wavelength between 400 nm to 3000 n

1. A method of locating tissue layers within a cornea, the cornea having an anterior surface, a posterior surface, and a photodisruption threshold, the method comprising the steps of: generating a pulsed laser beam from a femtosecond laser, the laser beam having a wavelength between 400 nm to 3000 nm and a pulse width from 100 femtoseconds to 10 nanoseconds;focusing the laser beam to a laser spot having an energy level such that the irradiance of the laser spot is below the photodisruption threshold of the cornea;varying a position of the laser spot between the anterior surface of the cornea and the posterior surface of the cornea and across at least one transition of the tissue layers, a harmonic signal being produced as the laser spot propagates in the cornea wherein the harmonic signal has an intensity correlated with a density of the cornea; anddetermining the transition of the tissue layers based on a change in the harmonic signal, the change comprising a change in the intensity of the harmonic signal. 2. The method of claim 1, further comprising determining a thickness between a first tissue layer of the tissue layers and a second tissue layer of the tissue layers based on the transition of the tissue layers. 3. The method of claim 1, wherein the tissue layers comprise one or more of the group consisting of an epithelium, a Bowman's layer, a stroma, a Descemet's membrane, and an endothelium. 4. The method of claim 1, wherein the varying step comprises continuously varying a position of the laser spot between the anterior surface of the cornea and the posterior surface of the cornea. 5. The method of claim 1, wherein the varying step comprises varying a position of the laser spot in increments between the anterior surface of the cornea and the posterior surface of the cornea. 6. The method of claim 1, further comprising determining multiple transitions of the tissue layers at various locations across the cornea. 7. The method of claim 1, further comprising generating a three dimensional model of the tissue layers. 8. The method of claim 1, further comprising applanating the cornea prior to determining the transition of tissue layers. 9. The method of claim 1, further comprising calibrating a focal depth of the laser spot based on the transition of the tissue layers. 10. An apparatus for determining a depth measurement and incising a cornea, the cornea having a photodisruption threshold, the apparatus comprising: a first input operable to receive a first input signal indicating a focal depth of a pulsed laser beam within the cornea, the laser beam having a wavelength between 400 nm to 3000 nm, a pulse width from 100 femtoseconds to 10 nanoseconds, and a pulse energy below the photodisruption threshold;a second input operable to receive a second input signal representing a harmonic of the laser beam generated as the laser beam propagates in the cornea;an output; anda processor coupled to the first input, the second input, and the output, the processor configured to: detect a change in the second input signal, the change indicating a tissue layer interface within the cornea as the focal depth of the laser beam is varied within the cornea and across the tissue layer interface;correlate the focal depth of the laser beam with the tissue layer transition to provide a reference depth of the laser beam; andtransmit an output signal via the output, the output signal indicating the reference depth of the laser beam. 11. The apparatus of claim 10, wherein the cornea has a Bowman's layer, a stroma, and an epithelium, and wherein the processor is further configured to: determine a first tissue layer transition between the Bowman's layer and the stroma based on a first change in the second input signal; anddetermine a second tissue layer transition between the Bowman's layer and the epithelium based on a second change in the second input signal. 12. The apparatus of claim 10, wherein the cornea has an anterior surface and a posterior surface, and wherein the processor is further configured to determine a distance from an anterior surface of the cornea to the tissue layer transition. 13. The apparatus of claim 12, wherein the cornea has a stroma, and wherein the processor is further configured to determine an incision depth of the laser beam based on the tissue layer transition, the incision depth being within the stroma. 14. The apparatus of claim 12, wherein the processor is further configured to: determine multiple tissue layer transitions in the cornea based by detecting different changes in the second input signal; andgenerate a three dimensional model based on the multiple tissue layer transitions. 15. The method of claim 1, wherein the energy level of the laser spot is below 1 μJ. 16. The apparatus of claim 10, wherein the laser beam has a pulse energy of below 1 μJ. 17. A system for locating tissue layer transitions within a cornea having an anterior surface, a posterior surface, and a photodisruption threshold, the system comprising: a laser subsystem including a femtosecond laser generating a pulsed laser beam having a wavelength between 400 nm to 3000 nm and a pulse width from 100 femtoseconds to 10 nanoseconds, the laser subsystem being configured to scan a laser spot of the pulsed laser beam between the anterior surface of the cornea and the posterior surface of the cornea and across one or more tissue layer transitions, the laser spot having an energy below the photodisruption threshold, a harmonic signal being produced as the laser spot propagates in the cornea;a sensor configured to detect the harmonic signal; anda processor coupled to the sensor and the laser subsystem, the processor configured to: monitor a location of the laser spot within the cornea;measure a change in the harmonic signal; andcorrelate the location of the laser spot within the cornea with the change in the harmonic signal to determine a tissue layer transition within the cornea. 18. The system of claim 17, wherein the cornea has adjacent tissue layers with different harmonic signals; and wherein the change in the harmonic signal indicates the tissue layer transition. 19. The system of claim 18, wherein the tissue layers comprise one or more of the group consisting of an epithelium, a Bowman's layer, a stroma, a Descemet's membrane, and an endothelium. 20. The system of claim 18, wherein the processor is further configured to determine a distance between the tissue layer transition and the anterior surface of the cornea or the posterior surface of the cornea. 21. The system of claim 18, wherein the processor is further configured to determine a thickness of the tissue layers based on the harmonic signal. 22. The system of claim 17, wherein the laser subsystem comprises a femtosecond laser. 23. The system of claim 18, wherein the harmonic signal has an intensity; and wherein the change is based on a change in the intensity of the harmonic signal. 24. The system of claim 17, wherein the processor is further configured to generate a three dimensional model of the tissue layers based on the tissue layer transition. 25. The system of claim 17, wherein the laser subsystem is further configured to: output a pulsed incision beam having a pulse energy of greater than or equal to the photodisruption threshold; and incise the cornea with the pulsed incision beam based on the tissue layer transition. 26. The method of claim 17, wherein the energy of the laser spot is below 1 μJ.