Short pulse lasers are used for a variety of therapeutic applications in medicine. Recently ultra-short pulse lasers have gained prominence due to the reduction in collateral thermal damage to surrounding healthy tissue during tissue ablation. In this paper, ultra-short pulsed laser ablation of mouse skin tissue is analyzed by assessing the extent of damage produced due to focused laser beam irradiation. The laser used for this study is a fiber-based desktop laser (Raydiance, Inc.) having a wavelength of 1552 nm and a pulse width of 1.3 ps. The laser beam is focused on the sample surface to a spot size on the order of 10 microns, thus producing high peak intensity necessary for precise clean ablation. A parametric study is performed on in vitro mouse tissue specimens and live anaesthetized mice with mammary tumors through variation of laser parameters such as time-averaged laser power, repetition rate, laser scanning rate and irradiation time. Radial temperature distribution is measured using thermal camera to analyze the heat affected zone. Temperature measurements are performed to assess the peak temperature rise attained during ablation. A detailed histological study is performed using frozen section technique to observe the nature and extent of laser-induced damages.
Ultrashort laser pulses can be used to create high precision incision in transparent and translucent tissue with minimal damage to adjacent tissue. These performance characteristics meet important surgical requirements in ophthalmology, where femtosecond laser flap creation is becoming a widely used refractive surgery procedure. We summarize clinical findings with femtosecond laser flaps as well as early experiments with other corneal surgical procedures such as corneal transplants. We also review laser-tissue interaction studies in the human sclera and their consequences for the treatment of glaucoma.
Approximately five million people worldwide are blind due to complications from glaucoma. Current surgical techniques often fail due to infection and scarring. Both failure routes are associated with damaging surface tissues. Femtosecond lasers allow a method to create a highly precise incision beneath the surface of the tissue without damaging any of the overlying layers. However, subsurface surgery can only be performed where the beam can be focused tightly enough to cause optical breakdown. Under normal conditions, subsurface surgery is not possible since sclera is highly scattering. Using two independent methods, we show completely subsurface surgery in human sclera using a femtosecond laser. The first method is to make the sclera transparent by injecting a dehydrating agent. The second method is to choose a wavelength that is highly focusable in the sclera. Both methods may be applied in other tissues, such as skin. We show highly precise incisions in in vitro tissues. Subsurface femtosecond photodisruption may be useful for in vivo surgical technique to perform a completely subsurface surgery.
Laser induced optical breakdown (LIOB) in fluids produces a localized plasma, an expanding radial shock wave front, heat transfer from the plasma to the fluid, and the formation of cavitation bubbles. Collectively these phenomena are referred to as photodisruption. Subjecting photodisruptively produced cavitation bubble nuclei to an ultrasonic field can result in strong cavitation and local cellular destruction. The ability of ultrafast lasers to produce spatially localized photodisruptions with microJoule pulse energies in combination with the possibility of larger scale tissue destruction using ultrasound presents an attractive and novel technique for selective and non-invasive tissue modification, referred to as photodisruptively nucleated ultrasonic cavitation (PNUC). Optimization of PNUC parameters in a confocal laser and ultrasound geometry is presented. The cavitation signal as measured with an ultrasound receiver was maximized to determine optimal laser and ultrasound spatial overlap in water. A flow chamber was used to evaluate the effect of the laser and ultrasound parameters on the lysis of whole canine red blood cells in saline. Parameters evaluated included laser pulse energy and ultrasound pressure amplitude.
The eye is potentially an ideal target for high precision surgical procedures utilizing ultrafast lasers. We present progress on corneal applications now being tested in humans and proof of concept ex vivo demonstrations of new applications in the sclera and lens. Two corneal refractive procedures were tested in partially sighted human eyes: creation of corneal flaps prior to excimer ablation (Femto- LASIK) and creation of corneal channels and entry cuts for placement of intracorneal ring segments (Femto-ICRS). For both procedures, results were comparable to standard treatments, with the potential for improved safety, accuracy and reproducibility. For scleral applications, we evaluated the potential of femtosecond laser glaucoma surgery by demonstrating resections in ex vivo human sclera using dehydrating agents to induce tissue transparency. For lens applications, we demonstrate in an ex vivo model the use of photodisruptively-nucleated ultrasonic cavitation for local and non-invasive tissue interaction.
Subsurface photodisruption is shown to be an effective tool for cutting beneath the surface in human sclera. Using a dehydrating agent to reduce scattering by index matching, photodistruption is possible anywhere in the volume of the sclera. We examine incision in human sclera in vitro using scanning electron microscopy. We found a disorganized material filling the incision and penetrating into the adjacent tissue.
We evaluated the efficacy, safety, and stability of femtosecond laser intrastromal refractive procedures in ex vivo and in vivo models. When compared with longer pulsewidth nanosecond or picosecond laser pulses, femtosecond laser-tissue interactions are characterized by significantly smaller and more deterministic photodisruptive energy thresholds, as well as reduced shock waves and smaller cavitation bubbles. We utilized a highly reliable, all-solid-state femtosecond laser system for all studies to demonstrate clinical practicality. Contiguous tissue effects were achieved by scanning a 5 μm focused laser spot below the corneal surface at pulse energies of approximately 2 - 4 microjoules. A variety of scanning patterns was used to perform three prototype procedures in animal eyes; corneal flap cutting, keratomileusis, and intrastromal vision correction. Superior dissection and surface quality results were obtained for lamellar procedures (corneal flap cutting and keratomileusis). Preliminary in vivo evaluation of intrastromal vision correction in a rabbit model revealed consistent and stable pachymetry changes, without significant inflammation or loss of corneal transparency. We conclude that femtosecond laser technology may be able to perform a variety of corneal refractive procedures with high precision, offering advantages over current mechanical and laser devices and techniques.
We investigated three potential femtosecond laser ophthalmic procedures: intrastromal refractive surgery, transcleral photodisruptive glaucoma surgery and photodisruptive ultrasonic lens surgery. A highly reliable, all-solid-state system was used to investigate tissue effects and demonstrate clinical practicality. Compared with longer duration pulses, femtosecond laser-tissue interactions are characterized by smaller and more deterministic photodisruptive energy thresholds, smaller shock wave and cavitation bubble sizes. Scanning a 5 (mu) spot below the target tissue surface produced contiguous tissue effects. Various scanning patterns were used to evaluate the efficacy, safety, and stability of three intrastromal refractive procedures in animal eyes: corneal flap cutting, keratomileusis, and intrastromal vision correction (IVC). Superior dissection and surface quality results were obtained for the lamellar procedures. IVC in rabbits revealed consistent, stable pachymetric changes, without significant inflammation or corneal transparency degradation. Transcleral photodisruption was evaluated as a noninvasive method for creating partial thickness scleral channels to reduce elevated intraocular pressure associated with glaucoma. Photodisruption at the internal scleral surface was demonstrated by focusing through tissue in vitro without collateral damage. Femtosecond photodisruptions nucleated ultrasonically driven cavitation to demonstrate non-invasive destruction of in vitro lens tissue. We conclude that femtosecond lasers may enable practical novel ophthalmic procedures, offering advantages over current techniques.