A history of the femtosecond laser in the United States and Europe

Johannes Kepler, a world-renowned astronomer and mathematician, published Dioptrice in 1611.¹ This classical literature laid the groundwork for optical instruments such as the telescope and introduced the diopter, a unit of measurement central to our work in cataract and refractive surgery. Today, we strive to achieve 0 diopters (ie, emmetropia) and spectacle independence for our patients, a goal made increasingly attainable through advances in technology, including the femtosecond laser.

Significant early milestones

The principles of femtosecond lasers were first described in 1986 by Gérard Mourou and Donna Strickland, who were both awarded the Nobel Prize in Physics in 2018 for their pioneering work.² The femtosecond laser offers the safest and most tissue-sparing way to cut an organ and perform surgery on a human being.

The journey of the femtosecond laser in ophthalmology began in 1992. Years before, in 1975, photodisruption of ocular tissue with high pulses in the nanosecond and picosecond range was achieved.³ However, the energy required to create the pulses caused mechanical and thermal adverse effects, such as bubble formation. Over time, incremental improvements in laser technology, including the shortening of pulse duration to femtoseconds, opened new opportunities and overcame the obstacles of high-pulse energy. This early milestone made refractive corneal surgery a reality.

Despite initial challenges with lenticule extraction from the cornea, the creation of a corneal flap marked the second significant early milestone for femtosecond lasers. In 1993, an accidental laser injury to the eye of a graduate student at the University of Michigan revealed the potential of femtosecond lasers for ocular surgery.⁴ Ron Kurtz, MD, the on-call ophthalmologist at the time, observed that the laser beam burned a precise circular silhouette in the student’s retina. This incident led to the revolutionary development of laser-assisted in situ keratomileusis (LASIK).

Key innovators, like Kurtz; Tibor Juhasz, PhD; and Mark S. Blumenkranz, MD, MMS, played pivotal roles in the collaborative innovation that led to the IntraLase femtosecond laser platform (iFS Advanced Femtosecond Laser; Johnson & Johnson Vision). This invention replaced the mechanical microkeratome with a safer, more precise option for LASIK flap creation.⁵

Europe also contributed significantly to the evolution of femtosecond laser technology. In 1999 in Hungary, Imola Ratkay-Traub, MD, PhD, was the first surgeon in Europe to perform a refractive surgery procedure with a femtosecond laser. She later went on to publish the first clinical results, concluding that “femtosecond lasers can produce precise intrastromal cutting, offering significant safety and other advantages [no razor blades, corneal trauma, partial resections, or sterilization issues] over current techniques.”⁶ This was a monumental step forward, especially considering Hungary’s pivotal role in overcoming the division of Europe during the Cold War.

The military also recognized the benefits of femtosecond laser surgery. A 2006 US Naval study concluded that military pilots who underwent femtosecond LASIK recovered faster and had better vision than those who underwent conventional LASIK with a mechanical microkeratome,⁷ leading to wider acceptance of the technology in the military.

Modern femtosecond lasers are now also used for lens-based refractive surgery procedures, such as refractive cataract surgery and refractive lens exchange. The LenSx Laser System (Alcon), developed by the same engineers who introduced femtosecond LASIK, marks the third early milestone of femtosecond lasers. It was the first femtosecond laser system designed for use in cataract surgery.

In August 2008, Zoltan Z. Nagy, MD, became the first surgeon worldwide to perform laser-assisted cataract surgery. The procedure was performed at the University Hospital of Budapest in Hungary. One year later, he published early clinical results showing that the femtosecond laser demonstrated higher precision of the capsulorhexis and reduced phaco power compared with a standard cataract surgery technique.⁸ Since then, various other platforms have been introduced, including the Catalys (Johnson & Johnson Vision), Femto LDV (Ziemer), Lensar Laser System and Ally Adaptive Cataract Treatment System (LENSAR, Inc), and Victus (Bausch + Lomb), providing reliable and safe options for laser-assisted cataract surgery.

Lenticule extraction is another exciting evolution in the history of femtosecond lasers. First performed by Walter Sekundo, MD, PhD, and Marcus Blum, MD, femtosecond lenticule extraction (FLEx) initially required a flap. The procedure was performed with the VisuMax femtosecond laser (Carl Zeiss Meditec). Sekundo’s group showed the procedure provided similar refractive outcomes to wavefront-optimized LASIK with significantly less induction of higher-order aberrations and better mesopic midterm contrast sensitivity.⁹

Other iterations of the FLEx procedure led to the development of small incision lenticule extraction (SMILE), now termed keratorefractive lenticule extraction. The procedure has gained popularity because of its precision, minimal pain, corneal stability, and low incidence of dry eye. As of August 2023, more than 8 million SMILE procedures had been performed.¹⁰ Today, other femtosecond laser platforms can be used to perform lenticule extraction, including the Atos (SCHWIND eye-tech-solutions GmbH), Elita (Johnson & Johnson Vision), and Femto LDV Z8 (Ziemer).

Applications beyond refractive surgery

The femtosecond laser’s applications are not limited to refractive surgery; it also has been used to increase the efficiency and safety of therapeutic interventions, including pockets for intrastromal corneal rings and inlays, and to improve vision in patients with keratoconus with techniques like corneal allograft intracorneal ring segments (CAIRS), which was introduced by Soosan Jacob, MS, FRCS, DNB, in 2018.¹¹ During CAIRS, allogenic rings or segments of various types and lengths are placed intracorneally to provide refractive and topographic effects. Today, the procedure can also be customized to achieve variation in the amount of flattening.¹²

Another development in this area has been customized keratoplasty techniques, such as penetrating keratoplasty, anterior lamellar keratoplasty, deep anterior lamellar keratoplasty, Descemet stripping automated endothelial keratoplasty, and Descemet membrane endothelial keratoplasty. These rely on the femtosecond laser to create complex graft-host junctions by customizing the thickness and shape of the graft and creating special wound configurations. Customized keratoplasty with femtosecond lasers can promote wound healing and accelerate visual rehabilitation.¹³

Even with these advances, femtosecond laser technology faces challenges in widespread adoption for therapeutic corneal procedures due to issues like corneal compression formation.¹⁴ The cost-effectiveness of such procedures also limits applications of the femtosecond laser for therapeutic corneal procedures.¹³

The future is femtosecond

Looking ahead to future promises, I have my eyes on the progress being made in laser-induced refractive index change (LIRIC). This approach may likely be a major step forward in corneal refractive surgery. Developed in collaboration with SCHWIND eye-tech-solutions and our clinic, LIRIC is a tissue-sparing procedure that modifies the refractive index of the cornea precisely and without compromising its structural integrity. This is achieved by altering its fibril density without removing or disrupting collagen. The laser, which operates at a wavelength of 405 nm, has potential applications for the treatment of myopia, hyperopia, and mixed astigmatism.15,16 In short, a low pulse energy and a high repetition rate denature the collagen fibers and dehydrate the treated area.

Conclusion

The femtosecond laser’s journey, both in the United States and Europe, has been marked by innovation, collaboration, and significant contributions to improving patient outcomes. As we continue to explore new applications and refine existing techniques, the future of femtosecond laser technology in ophthalmology looks incredibly promising.

References:

1. Kepler J. Dioptrice. 1611. Accessed July 31, 2024. https://archive.org/details/DioptriceByJohannesKeplerAkaIoannisKepleri

2. Nobel prize for pioneers in ultrashort pulsed laser technology. Trumpf. October 5, 2018. Accessed July 31, 2024. https://www.trumpf.com/it_IT/newsroom/comunicati-stampa-internazionali/comunicato-stampa-pagina-con-i-dettagli/release/nobel-prize-for-pioneers-in-ultrashort-pulsed-laser-technology/

3. Krasnov MM. Laser-phakopuncture in the treatment of soft cataracts. Br J Ophthalmol. 1975;59(2):96-98. doi:10.1136/bjo.59.2.96

4. Wright K. Laser-accident-turned-surgery breakthrough wins golden goose. Physics. September 14, 2022. Accessed August 24, 2024. https://physics.aps.org/articles/v15/141

5. Salomão MQ, Wilson SE. Femtosecond laser in laser in situ keratomileusis. J Cataract Refract Surg. 2010;36(6):1024-1032. doi:10.1016/j.jcrs.2010.03.025

6. Ratkay-Traub I, Ferincz IE, Juhasz T, Kurtz RM, Krueger RR. First clinical results with the femtosecond neodynium-glass laser in refractive surgery. J Refract Surg. 2003;19(20):94-103. doi:10.3928/1081-597X-20030301-03

7. Schallhorn SC, Tanzer DJ. Refractive surgery in Naval aviation. Presented at: Aerospace Medical Association Annual Meeting; May 14-18, 2006; Orlando, FL.

8. Nagy Z, Takacs A, Filkorn T, Sarayba M. Initial clinical evaluation of an intraocular femtosecond laser in cataract surgery. J Refract Surg. 2009;25(12):1053-1060. doi:10.3928/1081597X-20091117-04

9. Gertnere J, Solomatin I, Sekundo W. Refractive lenticule extraction (ReLEx flex) and wavefront-optimized femto-LASIK: comparison of contrast sensitivity and high-order aberrations at 1 year. Graefes Arch Clin Exp Ophthalmol. 2013;251(5):1437-1442. doi:10.1007/s00417-012-2220-4

10. Zeiss surpasses 8 million eyes treated with SMILE worldwide. Eyewire. August 23, 2023. Accessed July 31, 2024. https://eyewire.news/news/zeiss-surpasses-8-million-eyes-treated-with-smile-worldwide?c4src=article:infinite-scroll

11. Jacob S, Patel SR, Agarwal A, Ramalingam A, Saijimol AI, Raj JM. Corneal allogenic intrastromal ring segments (CAIRS) combined with corneal cross-linking for keratoconus. J Refract Surg. 2018;34(5):296-303. doi:10.3928/1081597X-20180223-01

12. Jacob S, Agarwal A, Awwad ST, Mazzotta C, Parashar P, Jambulingam S. Customized corneal allogenic intrastromal ring segments (CAIRS) for keratoconus with decentered asymmetric cone. Indian J Ophthalmol. 2023;71(12):3723-3729. doi:10.4103/IJO.IJO_1988_23

13. Liu C, Mehta JS, Liu YC. Femtosecond laser-assisted corneal transplantation. Taiwan J Ophthalmol. 2023;13(3):274-284. doi:10.4103/tjo.TJO-D-23-00080

14. Petznick A. Femtosecond-laser assisted cataract surgery – a clinical perspective. Alcon Inc; 2021. Accessed August 23, 2024. https://alcon.widen.net/s/trsjfsnlh9/femtosecond-assisted-lasik-flap-versus-microkeratome-assisted-lasik-flap-creation-us-lsx-2100003

15. Ding L, Knox WH, Bühren J, Nagy LJ, Huxlin KR. Intratissue refractive index shaping (IRIS) of the cornea and lens using a low-pulse-energy femtosecond laser oscillator. Invest Ophthalmol Vis Sci. 2008;49(12):5332-5339. doi:10.1167/iovs.08-1921

16. Savage DE, Brooks DR, DeMagistris M, et al. First demonstration of ocular refractive change using blue-IRIS in live cats. Invest Ophthalmol Vis Sci. 2014;55(7):4603-4612. doi:10.1167.iovs.14-14373

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