INTRODUCTION
The history of medicine is replete with instances of path-breaking discoveries and inventions, which have had a significant impact on mankind. Light amplification by stimulated emission of radiation (LASER) is an instance of one such landmark development, which has changed the management of numerous diseases in the field of medicine, especially in ophthalmology. We have briefly outlined the evolution of lasers in ophthalmology, with an emphasis on femtosecond laser technology. The changing paradigm of cornea-based refractive surgeries has been described, from the early mechanical reshaping of the cornea to the present day flapless femtosecond laser-assisted refractive lenticule extraction (Flowchart 1.1).
LASERS IN OPHTHALMOLOGY: A BRIEF HISTORY
Today, one tends to associate the term LASER with precision, accuracy and speed. However, its evolution has taken decades of work by numerous scientists around the world. The use of light as a therapeutic agent in ophthalmology dates back to the 1940s, when Meyer-Schwickerath first focused strong sunlight on the retina of patients with choroidal melanomas in order to treat them.1 The concept of stimulated emission was introduced by Einstein in 1917.2 Townes and Schawlow used microwave radiation as the external source for stimulated emission and developed microwave amplification by stimulated emission of radiation (MASER). Gordon provided the concept of using light as the source for stimulated emission, and thus coined the term light amplification by stimulated emission of radiation or LASER.3
Laser radiation has the advantage of being highly coherent, monochromatic and collimated. The first functional laser was developed by Maiman in 1960.4 Zaret produced the first ocular lesion using ruby laser in 1961.5 In 1964, Bridges developed the argon laser with emission in the blue and green wavelengths.6 In 1970, Basov built a laser using xenon dimer gas, and called it excimer laser (an abbreviation for excited dimer).72
3Argon fluoride laser, a type of excimer laser, was developed in 1976, with emission in the ultraviolet range at a wavelength of 193 nm.8
CORNEAL REFRACTIVE SURGERY: TRACING THE BEGINNING
The history of corneal refractive surgery dates back to the year 1896, when Lendeer Jans Lans gave the idea of reshaping the cornea for correcting corneal astigmatism using penetrating corneal cuts. He concluded that traverse incisions flattened the cornea in the meridian perpendicular to the incisions.9
Decades later, in the 1930s, Tsutomu Sato conceptualized this principle in the form of the technique of radial keratotomy, a procedure which was later popularized by Fyodorov et al. Sato had observed a flattening effect in the cornea of keratoconus patients after an episode of acute hydrops. He subsequently created both anterior and posterior corneal incisions to cause flattening in order to correct myopia. Radial keratotomy gained immense popularity during the 1970s and 1980s for the surgical correction of myopia.10
In 1964, Jose Ignacio Barraquer, belonging to the third generation of a family of famous ophthalmologists in Spain, introduced the idea of keratomileusis, which literally meant corneal carving. He used a manual microkeratome for lamellar dissection of cornea. The disc, thus obtained, was frozen (with liquid nitrogen or solid carbon dioxide) and cryolathed on its posterior surface based on the refractive correction required. This disc was then sutured onto the corneal stromal bed. However, the technique was not very suitable to correct astigmatism.11 Later on, his pupils developed the Barraquer-Krumeich-Swinger (BKS) nonfreeze technique, which did not require the freezing of the dissected corneal disc, thereby leading to fewer postoperative complications and faster visual recovery.12 Ruiz modified the technique by doing an in situ keratomileusis, wherein he resected a layer of tissue from the stromal bed itself by passing the microkeratome at a different depth after making the initial cap. He is also credited with the development of an automated microkeratome, producing a more regular corneal surface with greater precision. He demonstrated the formation of a corneal flap by stopping the microkeratome head before the end of the pass, followed by stromal bed resection and repositioning of the flap. This helped in avoiding the cap related complications.13,14
The introduction of argon fluoride laser in 1981 heralded a major breakthrough in the field of refractive surgery. It allowed enhanced precision levels and led to the creation of clean, etched-out lesions with minimal collateral damage.
The utility of excimer laser was subsequently expanded to radial keratotomy as well as photorefractive keratectomy (PRK).15–184
Pallikaris described the present technique of laser-assisted in situ keratomileusis (LASIK) in 1991. He created a hinged corneal flap using a guarded microkeratome followed by excimer laser-assisted stromal ablation.19
The late 1980s and early 1990s witnessed an increasing use of picosecond and nanosecond lasers for in situ keratomileusis and corneal flap creation. These lasers were the precursors of femtosecond lasers, which were introduced in the subsequent decade.
In 1996, Ito et al. attempted the use of a 1,053 nm picosecond laser (10−12) to create a corneal flap as well as a stromal lenticule in experimental rabbit eyes. The infrared picosecond laser replaced the functions of microkeratome and excimer laser, and this experimental technique formed the basis of refractive lenticule extraction by Sekundo et al. in 2008.20 In 1998, Krueger et al. used the picosecond laser [Neodymium-doped yttrium lithium fluoride (Nd:YLF), 1053 nm; energy: 25 µJ/pulse, 30 picoseconds] in a case with −15 D myopia to create the corneal flap and perform excimer laser- assisted stromal ablation. They also attempted both flap creation and stromal lenticule creation [again, a precursor to femtosecond lenticule extraction (FLEx)] with the picosecond laser.21 Krueger et al. (1996) evaluated the corneal stroma ultrastructure after picosecond laser photodisruption and observed multiple, coalescing intrastromal cavities parallel to the corneal surface, without any thermal necrosis or coagulative change in the region of tissue interaction.22 The incision quality and precision produced by picosecond lasers were comparable to that produced by excimer laser.23
FEMTOSECOND LASERS IN CORNEAL REFRACTIVE SURGERY
Femtosecond lasers in ophthalmology were introduced by Kurtz et al. in 1998, who created corneal flaps in primate cadaver eyes with high precision and smooth lamellar dissection planes.24 Dr Tibor Juhasz and his team are credited with designing and building the first surgical ophthalmic femtosecond laser system. He worked in collaboration with Dr Kurtz and his associates to develop the laser parameters for use in corneal refractive surgery.25 Laser pulses of ultrashort duration of the order of 10−15 seconds were focused 150–200 microns below the epithelial surface and delivered in a spiral pattern. Tissue dissection was achieved best at pulse energies ranging from 4 µJ to 8 µJ and spot separations of 10–15 microns.
The first Food and Drug Administration (FDA) approved femtosecond laser for ophthalmological use was IntraLase Pulsion. It was approved in the year 2000 for lamellar corneal surgery and became commercially available for creation of corneal flap in LASIK surgery by 2001. The laser spots were delivered in a spiral pattern. The earlier models were of the low frequency and high energy. The first generation IntraLase Pulsion femtosecond laser 5(Abbott Medical Optics) had a frequency of only about 10 kHz. With technological advancements, higher frequencies and lower energies were targeted. This translated to greater cutting speeds, more efficient tissue cutting and less spill-over effect on the adjacent tissue. The second and third generation IntraLase laser systems had a frequency of 15 kHz and 30 kHz, respectively, while the energy delivered lowered to 2.9 µJ and 1.7 µJ. The lower energy systems require closer spacing of the laser spots. The fifth generation IntraLase femtolaser received FDA approval in 2008 for FS-LASIK (Femtosecond-LASIK). It had a planar applanation system with a frequency of 150 kHz and could create a flap in about 10 seconds.
In 2007, VisuMax laser (200 kHz) was approved for its laser microkeratome function by the FDA. The currently available VisuMax laser (Carl Zeiss Meditec AG) has a frequency of 500 kHz with each pulse conveying energy of about 150 nJ. The laser spots have 1 μm diameter and are placed at a distance of 2–5 μm in a spiral pattern. The VisuMax laser, unlike the IntraLase, has a curved applanation surface which causes less corneal distortion and minimizes intraocular pressure (IOP) spikes. The other femtosecond laser systems approved for femto-LASIK include the Femtec (Technolas Perfect Vision), Femto LDV (Ziemer Ophthalmic Systems AG), and Wavelight FS200 (Alcon Surgical).
The femtosecond laser technology has evolved from the early laser systems with a low repetition rate (10 kHz) which needed higher energy to operate, to the newer devices having a higher repetition rate (as high as 500 kHz), with lesser energy utilization, shorter procedure duration and better surface quality.26 In addition to refractive surgery, femtosecond lasers have found applications in tunnel creation for intracorneal ring segments (INTACS), astigmatic keratotomy, keratoplasty (both penetrating and lamellar) and cataract surgery.
The femtosecond lasers were a major advancement over the microkeratome in being able to make thinner flaps which were more precise and thus, associated with fewer flap-related complications and corneal biomechanical changes.27
In the year 2000, Holger et al. used Ti-sapphire femtosecond laser in porcine eyes to create corneal flaps and stromal lenticules. They observed enhanced precision of stromal cuts with pulse energies of 1–2 µJ (lower than that used by Kurtz et al.), spot size of 5–10 microns and spot separation of 8 microns. The thermal alteration of adjacent tissue was of the order of only 1 micron.28 Subsequently, in 2003, Heisterkamp et al. successfully demonstrated the use of femtosecond laser in rabbit corneas for creation of the anterior corneal flap and stromal lenticule, which was extracted after lifting the flap. They proposed femtosecond laser to be a suitable replacement for both microkeratome and excimer laser.296
In 2003, Ratkay-Traub et al. published the clinical results of use of femtosecond neodymium-glass laser on human eyes. It was used to create the corneal flap, perform keratomileusis and create channels for intrastromal ring segments. Comparable results were observed between FS-LASIK and microkeratome-LASIK. Femtosecond laser created precise stromal cuts with additional advantages over the mechanical methods.30
The evolution of refractive lenticule extraction marked the next major breakthrough in the field of refractive surgery. Sekundo et al. introduced the technique of FLEx in 2008, which involved a femtosecond laser-assisted creation of a flap as well as a refractive lenticule. The femtosecond laser flap was lifted akin to the LASIK flap, and the underlying refractive lenticule was dissected from the stromal bed and extracted.31 At present, the VisuMax (Carl Zeiss Meditec, Jena, Germany) laser platform is the only commercially available system that allows refractive lenticule creation. Though the new procedure of refractive lenticule extraction was observed to be safe and efficacious, it did not lead to a decrease in the flap-related complications.32 There was a need for superior procedures that eliminated the need for a corneal flap. This led to the evolution of small incision lenticule extraction (SMILE) in 2010. Sekundo et al. described the creation of an intrastromal refractive lenticule that could be extracted through two small side-cut incisions of 80° chord length, placed 180° apart. Although the lenticule dissection and extraction is more challenging, the technique is associated with a significantly decreased incidence of microstriae and dry eyes as well as an improved internal structural stability. SMILE became available for commercial use in 2011.33
The initial VisuMax laser system used for SMILE had a frequency of 200 kHz. The new 500 kHz VisuMax femtosecond laser received the FDA approval for SMILE in September 2016. It is currently approved to treat myopia ranging from −1.00 D to −8.00 D of myopia, with less than or equal to −0.50 D cylinder and manifest refraction spherical equivalent (MRSE) less than or equal to −8.25 D. It is not yet approved for treating astigmatism or hyperopia. Currently, trials are ongoing to evaluate the safety and efficacy of SMILE in higher degrees of myopia, as well as astigmatism and hyperopia.
CONCLUSION
Femtosecond laser technology was introduced in the field of refractive surgery in 2001 for the creation of lamellar corneal flaps to allow subsequent excimer laser ablation. The initial high-energy, low pulse femtolaser systems have evolved to present day low energy, high-pulse systems with enhanced precision and minimum collateral damage. The most recent innovation of flapless intrastromal lenticule extraction has marked a significant leap forward, with the elimination of flap-related complications, improved biomechanical stability and a better-preserved ocular surface. With further 7technological advancements, the refractive applications of this procedure will expand to encompass all types of refractive error with minimum complications and optimal outcomes.
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