**2. Historical background for development of femtosecond laser systems in ophthalmology**

Various laser sources were developed and pioneered by solid-state and organic dye lasers in the 1960s and early 1970s. In 1979, short-pulse lasers at near-infrared wavelengths were used in ophthalmology for the treatment of posterior capsule opacification after surgery (by Aron-Rosa). In the 1980s, research continued on non-linear effects in optical fibers and near-infrared spectral region; in 1982, the first Titane (Ti): sapphire laser was built by Moutan, which had a wide tuning range (680–1130 nm), which was based the tunable FSL source. Following the use of the coupled-cavity mode-locking technique with a Ti: sapphire laser to constitute the generation of sub-100 fs pulses, a new generation of FSL was generated, which matched the cavity containing the 'non-linear element' with interferometric precision to the master cavity of the color-center laser oscillator. With peak optical pulse powers of >5 MW from a Ti: sapphire laser, compared with the dye-laser pulse peak powers, oscillator-amplifier combinations were no longer required, but for using the optical Kerr effect, cavity-design parameters were required (**Figure 1**). In 1984, FS dye laser was used in oscillator-amplifier configurations, and in 1989, Stern and colleagues found that reducing the pulse duration of near-infrared laser from the nanosecond to the picosecond (10−12) and then FS (10−15) resulted in higher precision ablation profiles and less collateral damage. FS belongs to ultra-fast or ultra-short pulse lasers with a beam diameter of <8 microns in the near-infrared spectral region and is capable of producing smaller shock waves and cavitation bubbles that affect a tissue volume about 103 times less than picosecond-duration pulses [1].

The first prototype of the ophthalmic surgical FSL system was developed by Dr. Jujasz and colleagues and was clinically used by Dr. Kurtz at the University of Michigan in the early 1990s. The IntraLase Pulsion FSL was approved by the U.S. Food and Drug Administration (FDA) for lamellar corneal surgery in Jan. 2000, and the first commercial laser was introduced to the market in 2001 for the creation of the corneal flap in

**Figure 1.** *The diversity of ultrashort pulse laser oscillators.*

refractive surgery, i.e. laser in situ keratomileuses (LASIK). The advantages of this system caused FSL to replace the mechanical cutting devices shortly. In 2002, Advanced Medical Optics (IntraLase FS, Irvine, California, USA) fired a 10–kHz laser. In 2007, Ziemer FEMTO LDV™ introduced new low pulse energy with high frequency. The current IntraLase system has a pulse rate of 60 kHz, which enables shorter flap-cutting times, less energy to cut the flap, and closer separation of the spots and lines. The fifth generation of the IntraLase FS system fires at 150 kHz with high-precision computer control of the parameters, which enables cutting flaps in less than 10 seconds with a variety of geometric shapes, depths, diameters, wound configurations, energy, spot sizes, and spot separation, allowing for precise corneal cutting.

FSL has also been used for cataract surgery since 2008; the LensX™ system, approved for this procedure by FDA in 2009, opened another sector of ophthalmic FS-laser application. The early version operated at 33 kHz pulse frequency and 6–15 μJ energies. LensX was then integrated with Alcon, and similar products were launched by multiple manufacturers. In 2014, the first low pulse energy FSL system was introduced for cataract and cornea surgery, the Ziemer FEMTO LDV Z8™ [4].

Simultaneous with the development of FSL, optical coherence tomography (OCT) was also described (1988), which provided non-invasive 3D in vivo imaging with fine resolution (microscopic resolution of 5–20 μm) in both lateral and axial dimensions at a micrometer level. Several variations have been developed for OCT since its introduction and are currently used with FSL systems in most modern cataract procedures after docking the laser interface to the eye.

Fourier Domain Optical Coherence Tomography (FD-OCT) employed a fixed reference arm length but a spectrometer with a linear detector array instead of a single detector. In this scenario, optical path length variations between interferometer arms cause periodic interference modulation. By Fourier transformation, the measured spectrum can yield an A-scan. "Sweep-source" (SS) OCT is an improved frequencydomain OCT variant. A tunable light source with a "sawtooth" frequency profile over time is used with a fast single-pixel detector instead of a spectrometer. After docking the laser interface to the eye, most current cataract fs-lasers do three-dimensional OCT scans.

Also, a 3D confocal structured illumination is used with the Scheimpflug camera, which was first described by Theodor Scheimpflug in 1904, and is currently used in LENSAR™ system. Therefore, the integration of FSL processing with optical devices enabled new applications in ophthalmology [5]. Considering the day-to-day advancements of FSL, in this chapter, we describe the latest micromachining advancements in optical systems and devices.
