The development of photodisruption and its application in ophthalmology can be categorized into stages by the duration of the pulse width used to perform subsurface tissue alteration. For the first time in the 1970s, ophthalmologists were able to use nonlinear absorption to treat open-angle glaucoma with a Q-switched ruby laser.1 A decade later, surgeons started to use nonlinear ablation with a Q-switched Nd:YAG laser to cut the posterior capsule of the crystalline lens after posterior capsular opacification2,3 by inducing multiphoton absorption.
Around the same time, Josef Bille, PhD, and Stuart Brown, MD, discovered that they could create high intensity at considerably lower pulse energies by shortening the pulse duration of a laser platform, leading to higher precision in processing tissue. With Tibor Juhasz, PhD, as Chief Scientist, this team at the start-up company Intelligent Surgical Lasers engineered a prototype laser that operated at a 1,053-μm wavelength and emitted pulses of several tens of picoseconds duration and several millijoules of pulse energy.4,5 Although this laser did not achieve its intended goal—reproducible intrastromal ablations—it served as a steppingstone for the design of the first femtosecond laser.
Since the IntraLase femtosecond laser (now Abbott Medical Optics Inc.) was introduced for flap creation, four other refractive surgical femtosecond lasers have made their way to the market: the Femtec (Technolas Perfect Vision), the Femto LDV (Ziemer Ophthalmic Systems AG), the FS200 (Alcon Laboratories, Inc.), and the VisuMax (Carl Zeiss Meditec).
Ophthalmic femtosecond lasers promote safe surgery and fast healing times because they can process tissue and other materials within a 3-D volume without altering its surface. The success of this platform in refractive and, more recently, cataract surgery is based on two unique characteristics: (1) the nonlinear absorption process and (2) extremely high precision and low side effects resulting from the low energy level needed for photodisruption. With the laser’s nonlinear absorption process, the surgeon can process tissue three dimensionally without being limited by any surface. (This differs from linear absorption, such as in excimer laser corneal remodeling, which occurs directly at the surface of the absorbing tissue and is determined by the wavelength and the absorption characteristics of the tissue.) Femtosecond lasers have many ophthalmic applications, which are discussed below.
Imaging. Ophthalmic femtosecond lasers use a 3-D scanning procedure for tissue cutting. The same 3-D beam delivery used to disrupt tissue can also be used to image the cutting process before, during, and after surgery. The target tissue can be scanned for imaging without the addition of scanning mirrors or lenses. The first-generation of femtosecond laser cataract surgery already makes use of this unique feature by passing an optical coherence tomography (OCT) beam along the path of the laser beam to image the target tissue. This can be done before surgery to navigate the laser pulses.
This same feature is not yet in use in corneal refractive surgery femtosecond lasers, but it will no doubt be introduced as OCT technology becomes more affordable. Currently, only one femtosecond laser corneal surgical platform includes an imaging function, the CorneaSurgeon (Rowiak GmbH), which prepares corneal donor tissue for keratoplasty.
Femtosecond lasers can also be used to perform second harmonic imaging and multiphoton fluorescence imaging to supply high-resolution images,6-8 with the capability to deliver information about the anatomy as well as the metabolic conditions of the tissue.
Turbid tissue. Turbid corneal tissue induces very strong scattering. Fortunately, with long infrared wavelengths, scattering is very low, allowing turbid tissue to be processed at its surface, in deeper layers, and even in sclerotic crystalline lenses and scleral tissue.9-11 In the future, ophthalmologists may be able to use this function of the femtosecond laser to treat glaucoma with novel surgical procedures.
Processing speeds. Today, ophthalmic femtosecond lasers can deliver repetition rates in the kilohertz range with sufficiently high pulse energies. In the future, it may be possible to use laser delivery repetition rates in the megahertz range, further reducing treatment times.
Laser cataract surgery. This is the newest ophthalmic application of the femtosecond laser, with four companies paving the way in this arena: OptiMedica Corp., with its Catalys Precision Laser; LensAR, with the LensAR laser platform; Alcon Laboratories, Inc., with its LenSx laser platform; and Bausch + Lomb, with the Victus. The manufacturer of the Victus has stated that the laser has the capability of performing cataract as well as corneal refractive applications.
Treatment of tractional vitreous attachments. In the near future, ultrashort laser pulses may replace posterior vitrectomy for the treatment of tractional vitreous attachments. This noninvasive strategy requires some development before it is possible, as laser pulses delivered through the vitreous are distorted. This requires higher energy, causing acoustic shock waves and thermal damage. However, if adaptive optics can be successfully incorporated into the beam delivery, these optical aberrations may be eliminated, thus achieving a well-focused, highly resolved laser spot (Figure 1).12
Reversing presbyopia. Another promising application of the femtosecond laser is presbyopia reversal by restoring the flexibility of the crystalline lens. The hope is that the femtosecond laser can be used to create microincisions inside the lens without surgically opening the eye (Figure 2). These microchannels could reduce the inner friction of the lens tissue, acting as sliding planes. When delivered to rabbit eyes, these laser incisions did not cause cataract growth or wound-healing abnormalities. 13-15 When applied to human autopsy eyes, an average increase of 100 μm in the anteroposterior lens thickness was seen, corresponding to a 2.00 to 3.00 D gain in accommodative amplitude (Figure 3).
Refractive index shaping. If the intensity of the femtosecond laser remains just below the threshold of optical breakdown, it is possible to create low-density plasma, which will allow free electrons to interact with surrounding tissue. These chemical reactions could result in slight changes in the refractive index of optical media, and this phenomenon could be used to program diffractive lenses into the cornea or crystalline lens. In animal studies, refractive index shaping has been shown to be stable for several weeks or months;16 this principle could also be used to adjust the power of an IOL in situ.17
Corneal collagen crosslinking (CXL). Ultrashort laser pulses applied to the posterior cornea or to scleral tissue may be possible using two-photon absorption. Therefore, surgeons could apply CXL to deeper areas of the eye for further beneficial effects in patients with keratoconus.
Reversing cataract. Photo bleaching, or using multiphoton absorption to photochemically destroy absorbing, fluorescent, and scattering protein aggregates inside the nucleus, can remove the yellowing of the crystalline lens. In one experiment,18 human donor lenses were treated with an 800-nm infrared femtosecond pulsed laser. After treatment, the investigators found that the age-related yellow discoloration of the lens was reduced and the transmission of light increased. Finally, using coherent control, a quantum mechanical-based method for controlling dynamic light processes, it might be possible to selectively bleach the crystalline lens.19
High levels of surgical precision are possible with femtosecond lasers, and ophthalmologists have already made good use of this technology, originally in refractive surgery and now in cataract surgery as well. The frontiers of retinal and glaucoma surgery are not far behind.
- Femtosecond lasers promote safe surgery and fast healing times because they can process tissue and other materials within a 3-D volume without altering its surface.
- Useful features of femtosecond lasers include imaging ability, long infrared wavelengths, and high reptition rates.
- Potential applications include laser cataract surgery, treatment of tractional vitreous attachments, reversing presbyopia, refractive index shaping, CXL, and reversing cataract.
Holger Lubatschowski, PhD, is CEO at Rowiak GmbH, Germany. Professor Lubaschowski states that he has a financial interest in the field of femtosecond laser assisted surgery, and he is a shareholder in Rowiak GmbH. He may be reached at e-mail: H.Lubatschowski@Rowiak.de.
- Krasnov M.Laser puncture of anterior chamber angle in glaucoma (a preliminary report).Vestn Oftalmol. 1972;3:27-31.
- Aron-Rosa D,Aron JJ,Griesemann JC,Thyzel R.Use of the neodymium-YAG laser to open the posterior capsule after lens implant surgery:a preliminary report.J Am Intraocul Implant Soc.1980;6(4):352-354.
- Fankhauser F,Roussel P,Steffen J,Van der Zypen E,Chrenkova A.Clinical studies on the efficiency of high power laser radiation upon some structures of the anterior segment of the eye.First experiences of the treatment of some pathological conditions of the anterior segment of the human eye by means of a Q-switched laser.Int Ophthalmol. 1981;3(3):129-139.
- Remmel R,Dardenne C,Bille J.Intrastromal tissue removal using an infrared picosecond Nd:YLF ophthalmic laser operating at 1053 nm.Laser Light Ophthalmol.1992;4(3/4):169-173.
- Niemz MH,Hoppeler TP,Juhasz T,Bille J.Intrastromal ablations for refractive corneal surgery using picosecond infrared laser pulses.Laser Light Ophthalmol.1993;5(3):149-155.
- Gibson EA,Masihzadeh O,Lei TC,Ammar DA,Kahook MY.Multiphoton microscopy for ophthalmic imaging. J Ophthalmol.2011.doi:10.1155/2011/87079.
- Zipfel WR,Williams RM,Webb WW.Nonlinear magic:multiphoton microscopy in the biosciences.Nat Biotechnol. 2003;21(11):1369-1377.
- Helmchen F,Denk W.Deep tissue two photon microscopy.Nat Methods.2005;2(12):932-940.
- Sacks ZS,Kurtz RM,Juhasz T,Spooner G,Mouroua GA.Subsurface photodisruption in human sclera:wavelength dependence.Ophthalmic Surg Lasers Imaging.2003;34(2):104-113.
- Chai D,Chaudhary G,Mikula E,Sun H,Kurtz R,Juhasz T.In vivo femtosecond laser subsurface scleral treatment in rabbit eyes.Lasers Surg Med.2010;42(7):647-651.
- Plamann K,Aptel F,Arnold CL,et al.Ultrashort pulse laser surgery of the cornea and the sclera. J Optic. 2011;12(8).doi:10.1088/2040-8978/12/8/084002.
- Hansen A,Ripken T,Krueger RR,Lubatschowski H.Lowering threshold energy for femtosecond laser pulse photodisruption through turbid media using adaptive optics.Paper presented at:Ophthalmic Technologies XXI;January 22,2011;San Francisco.
- Krueger RR,Kuszak J,Lubatschowski H,Myers RI,Ripken T,Heisterkamp A.First safety study of femtosecond laser photodisruption in animal lenses:tissue morphology and cataractogenesis.J Cataract Refract Surg.2005;31(12):2386-2394.
- .Schumacher S,Oberheide U,Fromm M,et al.Femtosecond laser induced flexibility change of human donor lenses.Vision Res.2009;49(14):1853-1859.
- Lubatschowski H,Schumacher S,Fromm M,et al.Femtosecond lentotomy:generating gliding planes inside the crystalline lens to regain accommodation ability.J Biophotonics.2010;3(5-6):265-268.
- Ding L,Knox WH,Bühren,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.
- Bille JF.Generation and in situ modification of customized IOLs.Paper presented at:the ASCRS Symposium of Cataract,IOL and Refractive Surgery;March 28,2011;San Diego.
- Kessel L,Eskildsen L,van der Poel M,Larsen M.Non-invasive bleaching of the human lens by femtosecond laser photolysis.PLoS ONE.2011;5(3):e9711.
- König K,Uchugonova A,Straub M,et al.Sub-100nm material processing with sub-15 femtosecond picojoule near infrared laser pulses.Paper presented at:Multiphoton Microscopy in the Biomedical Sciences XI;January 23,2011; San Francisco.