Frieder Loesel

Corneal refractive surgery with femtosecond lasers

We investigated the use of ultrashort pulsed (femtosecond) laser technology in corneal refractive surgery. When compared to 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 practicality in real-world operating conditions. Contiguous tissue effects were achieved by scanning a 5-/spl mu/m focused laser spot below the corneal surface at pulse energies of approximately 2-4 /spl mu/J. 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 keratornileusis). Preliminary in vivo studies of intrastromal vision correction suggest that consistent refractive changes can also be achieved with this method. 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.

Second−harmonic imaging of cornea after intrastromal femtosecond laser ablation

Nonlinear laser scanning microscopy is widely used for noninvasive imaging in cell biology and tissue physiology. However, multiphoton fluorescence imaging of dense, transparent connective tissue (e.g., cornea) is challenging since sophisticated labeling or slicing is necessary. High-resolution, high-contrast second harmonic generation (SHG) imaging of corneal tissue based on the intrinsic structure of collagen is discussed. The three-dimensional corneal ultrastructure in depths up to hundreds of microns can be probed noninvasively, without any staining or mechanical slicing. As an important application of second harmonic imaging in ophthalmology, the modification of corneal ultrastructure using femtosecond laser intrastromal ablation is systematically investigated to evaluate next-generation refractive surgical approaches.

An in vivo model of femtosecond laser intrastromal refractive surgery.

BACKGROUND AND OBJECTIVE To develop an animal model for evaluation of femtosecond laser intrastromal refractive surgery. METHODS Intrastromal photodisruption was performed in New Zealand Albino rabbits using a femtosecond laser system. This surgical pattern consisted of a 100 microm-tick pyramid of laser pulses starting 180 microm below the corneal surface. Animals underwent serial slit lamp examinations and corneal thickness measurements at 1,3,7,14, and 28 days, then monthly up to 1 year. RESULTS Approximately 70 microm of central corneal thinning were seen at 1 week, remaining stable up to 7 months. CONCLUSIONS Intrastromal photodisruption with femtosecond lasers produced consistent changes in corneal thickness without loss of corneal transparency. These changes were more stable than those produced with excimer laser procedures in a similar animal model.

Laser spot size as a function of tissue depth and laser wavelength in human sclera

We determined the wavelength dependence of the minimum spot size of a laser beam focused through human sclera to evaluate the potential for transcleral glaucoma surgical techniques using ultrashort-pulsed lasers. The spectrum of the forward scattered light was measured by collimating the incident and transmitted beam in a spectrophotometer. This spectrum shows that sclera is highly scattering until 1100 nm, after which, the transmission spectrum is similar to water. To measure the minimal spot size, a laser beam was focused on the back surface of sclera of differing thickness. The minimum spot at 800 nm, 1060 nm, 1301 nm, and 1557 nm was imaged. At 800 nm, the spot size was invariant upon focal lens position, being a thousand fold larger than the incident beam spot size. As the wavelength increased, the area of the spot decreased, so that at 1557 nm, the minimal spot size was on the order of the incident beam spot size.

Plasma-mediated ablation of biological tissue with picosecond and femtosecond laser pulses

We investigated plasma-mediated surface ablation in corneal tissue using picosecond and femtosecond laser pulses in order to achieve high precision, non-thermal tissue removal with a non-ultraviolet laser source. Experiments utilized three laser systems, a regeneratively amplified Ti:sapphire laser, a synchronously amplified dye laser, and a regeneratively amplified picosecond Nd:YLF laser. Tissue ablation was performed by tightly focusing the laser beam on the tissue surface. Ablation thresholds were determined by monitoring the plasma spark, as well as the tissue surface. Tissue ablations were then analyzed by standard histologic methods and scanning electron microscopy. We observed a decrease in the ablation fluence threshold as the pulse duration is shortened from 200 ps to approximately 140 fs, in agreement with our theoretical predictions. Using identical pulse energies, the femtosecond laser pulses ablated tissue at higher efficiencies than the picosecond laser, with an approximately two-fold improvement in the etch depth curve. Histologic analysis reveal minimal adjacent tissue damage at either pulse duration. Femtosecond laser pulses may offer advantages that make them ideal tools for high precision tissue ablation.

Comparison of three different laser systems for application in dentistry

Three different laser systems have been investigated according to their possible application in dentistry: a free running and a Q-switched microsecond Ho:YAG laser, a free running microsecond Er:YAG laser and picosecond Nd:YLF laser system consisting of an actively mode locked oscillator and a regenerative amplifier. The experiments focused on the question if lasers can support or maybe replace ordinary drilling machines. For this purpose several cavities were generated with the lasers mentioned above. Their depth and quality were judged by light and electron microscopy. The results of the experiments showed that the picosecond Nd:YLF laser system has advantages compared to other lasers regarding their application in dentistry.

Noninvasive evaluation of mini-invasive femtosecond laser refractive surgery

Nd:glass femtosecond laser is promising as next generation mini-invasive eye surgical laser, with the advantages of excellent beam quality, high surgical precision and minimized side effects. However, there are still many open questions concerning the precision, efficiency and collateral effects of femtosecond laser refractive surgery. By non-invasive microscopic imaging methods including confocal, multiphoton, second harmonic and atomic force microscopy, we successfully characterized the three dimensional corneal ultrastructure without applying fixation and slicing. Based on the intrinsic properties of collagen, second harmonic cornea imaging proved to be outstanding to analyze the outcome of femtosecond laser intrastromal ablations. Strong contrast and large sensing depth second harmonic image was obtained without fixation, sectioning or labelling. The three dimensional ultrastructure of porcine cornea after Nd:glass femtosecond laser intrastromal surgery was examined to evaluate the concepts of minimum-invasive all-optical refractive eye surgery. No thermal damages were recognized and the surgical outcome appeared highly predictable. Due to the similarities between the physical principals of nonlinear laser scanning microscopy and femtosecond laser ablations, a setup of the Nd:glass femtosecond laser system integrating both the surgery and probing functions was proposed.

Femtosecond all-solid-state laser for refractive surgery

Refractive surgery in the pursuit of perfect vision (e.g. 20/10) requires firstly an exact measurement of abberations induced by the eye and then a sophisticated surgical approach. A recent extension of wavefront measurement techniques and adaptive optics to ophthalmology has quantitatively characterized the quality of the human eye. The next milestone towards perfect vision is developing a more efficient and precise laser scalpel and evaluating minimal-invasive laser surgery strategies. Femtosecond all-solid-state MOPA lasers based on passive modelocking and chirped pulse amplification are excellent candidates for eye surgery due to their stability, ultra-high intensity and compact tabletop size. Furthermore, taking into account the peak emission in the near IR and diffraction limited focusing abilities, surgical laser systems performing precise intrastromal incisions for corneal flap resection and intrastromal corneal reshaping promise significant improvement over todays Photorefractive Keratectomy (PRK) and Laser Assisted In Situ Keratomileusis (LASIK) techniques which utilize UV excimer lasers. Through dispersion control and optimized regenerative amplification, a compact femtosecond all-solid-state laser with pulsed energy well above LIOB threshold and kHz repetition rate is constructed. After applying a pulse sequence to the eye, the modified corneal morphology is investigated by high resolution microscopy (Multi Photon/SHG Confocal Microscope).

Ultraprecise medical applications with ultrafast lasers: corneal surgery with femtosecond lasers

We investigated refractive corneal surgery in vivo and in vitro by intrastromal photodisruption using a compact ultrafast femtosecond laser system. Ultrashort-pulsed lasers operating in the femtosecond time regime are associated with significantly smaller and deterministic threshold energies for photodisruption, as well as reduced shock waves and smaller cavitation bubbles than the nanosecond or picosecond lasers. Our reliable all-solid-state laser system was specifically designed for real world medical applications. By scanning the 5 micron focus spot of the laser below the corneal surface, the overlapping small ablation volumes of single pulses resulted in contiguous tissue cutting and vaporization. Pulse energies were typically in the order of a few microjoules. Combination of different scanning patterns enabled us to perform corneal flap cutting, femtosecond-LASIK, and femtosecond intrastromal keratectomy in porcine, rabbit, and primate eyes. The cuts proved to be highly precise and possessed superior dissection and surface quality. Preliminary studies show consistent refractive changes in the in vivo studies. We conclude that the technology is capable to perform a variety of corneal refractive procedures at high precision, offering advantages over current mechanical and laser devices and enabling entirely new approaches for refractive surgery.

Experimental and theoretical investigations on threshold parameters of laser-induced optical breakdown on tissues

The dependence of the fluence at the threshold of laser- induced optical breakdown on the laser pulse duration has been investigated experimentally and theoretically for human cornea, human enamel, and bovine brain tissue. For the experiments in the range from 100 fs to 200 ps, we used a femtosecond dye laser system and a picosecond Nd:YLF laser system. We observed a significant decrease of the fluence at the threshold when reducing the pulse duration. The measured dependence on the pulse duration is in good agrement with our model.