American Academy of Ophthalmology Web Site: www.aao.org
A FEMTOSECOND QUEST FOR SURGICAL PERFECTION
The femtosecond—a mere quadrillionth of a second— occupies a scale of time at which the wobbles of individual atoms and even quirky variances in the speed of light can be recorded. Albert Einstein himself might be tickled to find this zippy splinter of the fourth dimension forging a new frontier in medical technology.
Having improved outcomes in the field of refractive surgery, beginning with LASIK flap creation, the femtosecond laser is continuing to make great strides across a range of other anterior segment applications, from transplanting corneas and implanting intrastromal rings to perfecting the capsulotomy and blasting cataracts. But wait a minute—is that a price tag trailing those pulses of light? Is the femtosecond laser a transformative tool or an extravagant toy only a few can afford?
One answer comes from the increase in market share for femtosecond lasers purchased for LASIK flap creation—from 0 percent in 2001 to over 55 percent in 2010, as recorded in the industry publication Market Scope.
The clinical value of the femtosecond laser is still a matter of debate, but it has clearly made serious inroads in the field of anterior segment surgery. Several companies, including Abbott Medical Optics, Alcon, Carl Zeiss Meditec, Technolas Perfect Vision and Ziemer Ophthalmic Systems, are betting on community embrace of the laser’s potential, as they work to expand applications and vie for market share.
In addition to femtosecond’s use for LASIK flaps, the FDA has granted several femtosecond devices approval for other uses, including keratoconus treatment with intrastromal corneal ring segment placement, and shaped incisions for corneal transplantation and crystalline lens capsulotomies. A range of presbyopia procedures are also in the approval pipeline. Below is a look at the beginnings of the femtosecond laser and the surprising expansion of its applications.
Born of a Workplace Accident
The medical use of the femtosecond laser originated more than a decade ago at the University of Michigan in Ann Arbor, in a classic lemons-to-lemonade serendipity: A graduate student in the ultrafast lasers lab had sustained a well-defined laser burn on his retina, according to Shahzad I. Mian, MD, associate professor of ophthalmology and visual sciences at the university. “The examination of this burn by a second-year resident [Ron M. Kurtz, MD] led to collaborative research between the department of ophthalmology and the school of engineering, and ultimately to the original femtosecond medical laser, marketed as IntraLase in 2001.”
The laser’s delivery of power pulsed at high speeds generates microscopic gas bubbles that break bonds between cells in a process known as photodisruption. Despite femtosecond’s sophisticated applications across many disciplines, its principal mechanism remains simple, whether applied to industrial materials or human flesh (see “How Power Packs a Punch”).
Transection perfection. Similar to the workings of Nd:YAG laser, femtosecond offers precision that Nd:YAG lacks.1 “It allows us to cut clear tissue without generation of heat or requirement of pigment for absorption, and with minimal collateral damage,” said John A. Vukich, MD, assistant clinical professor of ophthalmology at the University of Wisconsin in Madison. “It can precisely transect tissue at any level that you wish to focus it.” This makes it possible to treat not only at the level of the cornea but also at the level of the anterior capsule or crystalline lens. And a patient’s anatomy—the steepness or thickness of the cornea, for example—doesn’t interfere with its cuts.
This laser is very fast, which enhances efficiency, said Sonia H. Yoo, MD, professor of ophthalmology at Bascom Palmer Eye Institute. “And because this is a largely automated technology-driven procedure, it’s not only better for patients but may also level the playing field for experienced and less-experienced surgeons.”
REFRACTIVE SURGERY: Flaps, Rings and Pockets
The femtosecond’s greatest contribution to ophthalmology thus far is certainly the safe and predictable creation of LASIK flaps. But many refractive surgeons and companies aren’t content to rest here.
No more flaps over flap making? “With the femtosecond laser, you can customize the configuration and shape of the flap, as well as where and how widely it’s attached,” said Dr. Mian. “And you can consistently make a flap as thick as you think you’re making it, so the margin of error is very low.”
Factors like these have virtually eliminated the serious complications related to the microkeratome, such as buttonhole or partial flaps, epithelial slough and significant epithelial ingrowth, and have led to superior wavefront outcomes, said Steven E. Wilson, MD, professor of ophthalmology and director of corneal research at Cleveland Clinic. If the surgeon loses suction on the pass, she or he can simply replace the suction head, then immediately complete the pass.
Many surgeons may share the sentiments of Dr. Wilson, who no longer anticipates his refractive cases with the same sense of dread as in the past: “I used to think, ‘I wonder what I will see tomorrow.’ Now, I never even give it a second thought. It’s so consistent, you know you’re going to have a good day.”
Confidence-building notwithstanding, last November’s issue of the Journal of Cataract and Refractive Surgery reported a comparison of microkeratome and femtosecond laser flaps and found that curiously dissimilar complications between the two did not add up to a net difference in LASIK outcomes. The conclusion reads thus: “Although the total complication rates between the two groups were similar, the microkeratome group had significantly more epithelial defects intraoperatively and the femtosecond laser group had significantly more diffuse lamellar keratitis cases postoperatively.”2
FLEx and SMILE. Femtosecond-only vision correction is now available outside the United States under Carl Zeiss Meditec’s ReLEx umbrella, which comprises both femtosecond lamellar extraction (FLEx) and small-incision lamellar extraction (SMILE), a slight evolution of FLEx. Using a curved applanation plate, the Zeiss VisuMax precisely cuts and removes a lenticule, rather than ablating.
The promise of a single laser platform like this for correcting refractive errors is appealing to surgeons like Dr. Yoo. “With the SMILE procedure, there’s the potential for a smaller incision and less destabilization of the corneal architecture,” she said, noting that the lenticule can be removed without lifting the flap. “If you could get the same refractive correction with even less dry eye and risk of ectasia, that would be a wonderful thing.”
Instrastromal correction for presbyopia. This procedure was pioneered by Luis Ruiz in Bogotá, Colombia, said Perry S. Binder, MD, clinical professor of ophthalmology at the University of California, Irvine. The technique creates five rings of shallow ablation within the cornea around the visual axis, without penetrating Bowman’s layer or Descemet’s membrane. “The rings are concentric, starting at 1.8 mm in diameter and extending outward, less than 0.5 mm from each other. The goal is to create a hyperprolate corneal shape for enhancing near vision to correct presbyobia and low amounts of hyperopia,” Dr. Binder said.
The 2008 European multicenter trial of the Technolas Perfect Vision Intracor refractive procedure reported positive results in correcting presbyopia, said Mike P. Holzer, MD, associate professor of ophthalmology and director of refractive surgery at the University of Heidelberg in Germany. Intracor has received CE Mark approval in Europe for presbyopia treatment, with recommended treatments ranging from +0.5 to +1.25 D with a maximum 0.5 D of cylinder.
Following the brief procedure, patients experienced significant improvement in near visual acuity the first postoperative day and, with two years of data, they showed no signs of regression or induced ectasia.3 By circumventing the corneal surface, said Dr. Holzer, this intrastromal femtosecond procedure also tends to lead to fewer corneal infections, less discomfort, faster recoveries and a quicker return to activity—usually on the first day postop.
“There is no other procedure for patients in this specific group—emmetropes with presbyopia—so it has really changed the refractive business here,” he said, although researchers are approaching the challenges of presbyopia from many angles, including using femtosecond laser to give the lens more elasticity.
Despite the promise of intrastromal corrections—which await further study in U.S. clinical trials—Dr. Wilson questions whether the femtosecond laser can reduce or prevent induction of aberrations in LASIK or PRK the way custom corneal ablations can. “I’m still open to the possibility,” he said, “but I don’t see how the technology can have the precision of an excimer laser. In addition, the only way to treat under- or overcorrections is with surface excimer laser surgery.”
Creating corneal pockets. Sophia I. Panagopoulou, PhD, researcher at the Institute of Vision and Optics and the University of Crete in Greece, is optimistic about the future of femtosecond technology. She and other members of a Crete team headed by Ioannis G. Pallikaris, MD, PhD, are using the IntraLase (AMO) femtosecond laser to create corneal pockets to insert the Flexivue intracorneal Micro-Lens (Presbia).
This is a minimally invasive, monovision technique for correcting presbyopia in emmetropes between the ages of about 45 and 60. The big advantage of this procedure is the possibility of exchanging the lens if the patient needs it. The femtosecond laser allows the precise and customized creation of the corneal pocket and subsequently the accurate and easy implantation of the Micro-Lens within the visual axis. With customization of the pocket a possibility, this can be used to simultaneously treat astigmatism up to 1 D.
This is especially valid for the new software available from IntraLase for creating corneal pockets. It simplifies the procedure and makes it possible to offer a new femto application to presbyopes. “Since this Micro-Lens is very thin and very small—3 mm in diameter and less than 20 µm in edge thickness—you always need the pocket into which you’re inserting it to be perfect,” said Dr. Panagopoulou. “You can have this with a ‘perfect knife,’ and, in this case, the ‘perfect knife’ is the femto.”
ReVision Optics and AcuFocus also use the AMO-designed software to insert inlays for the correction of presbyopia.
CATARACT SURGERY: A Good Procedure Gets Better?
“We’ve had no substantial innovation in cataract surgery since the advent of phacoemulsification,” said Dr. Vukich. Many surgeons believe that there are aspects of the operation that can be improved, and for this reason the femtosecond laser is capturing the imagination of cataract surgeons, he said.
Although Technolas Perfect Vision is the only femtosecond laser device that can perform both cataract and refractive surgery, LenSx (Alcon) has the most approvals for cataract surgery in the United States. LensAR’s laser, also approved, and OptiMedica’s are primarily designed to do nuclear fragmentation, said Dr. Binder, and other companies, including AMO, are strongly pursuing cataract options as well.
Improvements each step of the way. Incremental improvements are coming at all steps of the procedure—the keratotomy, capsulotomy and removal of the nucleus, said Dr. Vukich. “The femtosecond laser does all the things we currently do in cataract surgery; it simply does them more accurately and more reproducibly. Most would agree that it is very challenging to make the capsulotomy perfectly round, perfectly centered, and of the exact diameter that they wish every single time.”
Femtosecond laser also minimizes and, in some cases, eliminates the need for phaco by breaking up the nucleus into tiny cubes, which can then be aspirated from the eye. “When Charlie Kelman first introduced phacoemulsification, there were a lot of people who said, ‘What’s the point? We know how to remove a lens through an extracapular incision. Why would we want to do that?’” recalled Dr. Vukich. He believes the inexorable surge of advances that reduced extracapular cataract extraction to a procedure of historical interest in the developed world will also occur with femtosecond, taking cataract surgery to the next level.
One way it will do this, he said, is by optimizing the functionality of accommodative IOLs, which require reliable biomechanical coupling to the structures within the eye. “We’re trying to reproducibly leave behind a predictable amount of anterior capsule, to minimize torsional stress or trauma to the zonules during removal of the lens,” he said. “If we can pretreat the nucleus and make that easier, this certainly accomplishes that goal.”
Are the bar and price tag too high? Will femtosecond lasers improve cataract surgery such that they create a paradigm shift? Dr. Binder questions that. “If 92 percent of eyes are within a half-diopter of emmetropia and 96 percent have 20/20 vision or better, how much better can you make it with a perfectly circular capsulorhexis?” He agreed that the femtosecond is hoped to improve results with multifocal IOLs, but, interestingly, two out of three attendees polled in a cataract session at the Joint Meeting last October said they’d personally prefer a monofocal IOL for their own eye. “The lasers are elegantly designed, ergonomically excellent, have great software and great hardware, but I don’t think ophthalmology in 2011 can afford a half-million dollar machine with a click fee significantly greater than is current for LASIK surgeries,” Dr. Binder said. Dr. Wilson agreed with this perception, although he sees the potential for difficult cases being referred to tertiary centers equipped with femtosecond cataract technology in the future. And he sees this technology as especially useful for harder lenses and for beginning cataract surgeons where learning curves result in a higher incidence of posterior capsule disruption. “But I think it’s a pipe dream to think third party payers are going to adopt this when the current method is so effective.”
CORNEA SURGERY: Sharper Cuts, Smoother Layers
Scores of different approaches are used to perform corneal transplants. Imprecise, technically challenging and time-consuming, manual lamellar dissection can also produce topographical irregularities. And a large circumferential wound is susceptible to trauma and resulting loss of vision even years after penetrating keratoplasty. Microkeratome-assisted techniques have facilitated dissection and improved the smoothness of the lamellar surface but have not overcome technical and reproducibility challenges.1
For penetrating keratoplasty, the femtosecond laser offers precise bladeless cuts of any shape or pattern—whether top hat, mushroom, Christmas tree or zigzag—and at any depth, with trephination cuts available for both anterior and posterior lamellar transplantation.
In Descemet’s stripping automated endothelial keratoplasty, the femtosecond can also cut donor tissue. 1 “You can choose the angulation of the side cut,” said Dr. Holzer, “to improve the fit of the graft.” Being able to choose the size of the transplant and to individualize the whole cutting procedure is a big advantage, he said, suggesting it will be the wave of the future.
Involved in early animal and preclinical research for corneal transplantation years ago, Dr. Mian has conducted ongoing studies comparing standard approaches with those using femtosecond laser, which has compared favorably in small, peer-reviewed reports. Although prospective comparative trials are still needed, he said that early femtosecond studies have reported the following results:
Dr. Yoo is excited by the prospects of using femtosecond technology to eliminate the need for sutures. “We’re already able to do this with anterior lamellar keratoplasty,” she said. And she foresees a time when femtosecond laser may be combined with a bioadhesive to perform sutureless penetrating keratoplasty.
ENDLESS APPLICATIONS (and a Few Anxieties)
Applications for femtosecond laser are under relentless development, said Dr. Binder, and include corneal biopsy, wedge resection, corneal tattooing, collagen cross-linking, drug delivery and limbal stem-cell transplantation. “Anything you can cut in the eye, you can do with a femtosecond laser; that means scleral surgery, glaucoma surgery and iris surgery are certainly within the range of being attacked by femtosecond laser.”
Will expanding applications, greater availability, standardized protocols and more competition eventually drive costs down? That’s the hope. “The company that can do everything with one laser will certainly be more cost-effective,” said Dr. Mian.
In addition to reimbursement challenges, a few other technological issues remain, said Dr. Holzer. “The equipment around the femtosecond laser needs improvement, such as the accuracy of the corneal topographer to ensure reproducible cuts.” With cataract surgery, this means being able to measure the anterior chamber depth once the laser is connected. “You need a kind of online OCT built into the laser. We currently have the machine to change the corneal structure and the biomechanics. But we don’t have the machines to measure what we are changing.” (OptiMedica is developing just such a femtosecond laser platform with OCT imaging included—the Catalys Precision Laser System—but it is not yet marketed in the United States.)
It’s effective only if it’s easy. Logistics are also part of the equation, said Dr. Yoo. For example, making corneal cuts in the laser suite before transferring a patient to an operating room may limit the widespread use of femtosecond laser for corneal transplants.
Dr. Vukich has been consulting with OptiMedica to ensure that its cataract platform is integrated as efficiently as possible into physician practices, which means looking at issues such as location of the laser and ancillary instrumentation and enhancing flexibility to suit clinics of various sizes. “It won’t work for femtosecond procedures to be incrementally better, yet substantially worse in terms of patient flow,” he said. “A great deal of energy and care has gone into the design aspects. So we’re confident it will not substantially add to the operative time or related issues at the time of surgery.”
HOW POWER PACKS A PUNCH
Femtosecond lasers alternate pulses and pauses of energy that last approximately one-millionth of one-billionth of one second, each. For surgeons, femto speed offers intensely focused power delivered with minimal collateral damage.
Alan J. Hunt, PhD, director of the biomedical lab at the Center for Ultrafast Optical Science at the University of Michigan in Ann Arbor, explained the difference in power between long and short laser pulses. “For longer pulses the damage shows substantial variability from pulse to pulse. However, as pulses become very short the variability decreases, and the character of damage becomes more deterministic and predictable. This, coupled with a very abrupt energy threshold for the onset of damage, makes femtosecond damage easier to control and limits the damage to surrounding regions.”
This high-power/low-chaos approach to carving any material, biological or not, is explored with equally eloquent, atomic-level detail in a discussion of femtosecond machining published by the Department of Energy’s Brookhaven National Laboratory (minimally edited by EyeNet for length):
“Femtosecond laser micromachining utilizes ultrashort laser pulses to achieve an unprecedented degree of control in sculpting the desired microstructures without collateral damage to the surroundings. Using femtosecond rather than picosecond or nanosecond light pulses, laser energy is deposited in small volumes by multiphoton, nonlinear optical absorption, followed by avalanche ionization. Because typical heat diffusion time is in the order of a nanosecond to microsecond time scale, and the electron-phonon coupling time of most materials is in the picosecond to nanosecond scale, femtosecond laser energy is deposited at a rate much shorter than both heat transport and electron-phonon coupling, and the light-matter interaction process is essentially frozen in time. The affected zone is altered from solid to vapor phase and then to plasma formation almost instantaneously.”1
1 U.S. Department of Energy, Brookhaven National Laboratory, www.inst.bnl.gov/programs/laseropt/lasers/micromach.shtml.
Femtosecond technology was much discussed during the Academy’s 2010 Joint Meeting in Chicago. In fact, there was a special paper session on the topic. To view abstracts of those papers, scroll down. You will find abstracts on topics ranging from femtosecond-created capsulotomies to the laser’s use in customizing IOLs.
Purpose: To compare variability and predictability in effective lens position (ELP) by capsulotomy technique.
Methods: Forty eyes undergoing cataract surgery had either a femtosecond (FS)-created or a manual 4.5-mm capsulotomy followed by a single type of IOL. Postoperatively an optical biometer (Lenstar, Haag Streit) measured anterior chamber depth (ACD) and ACD-to-axial length ratio (ACDAL).
Results: At 1 month, there was reduced variability in the ELP of the FS compared to manual capsulorrhexis group (F test, P < .05).
Conclusion: Use of a femtosecond laser to perform capsulotomy demonstrates less variability in ELP. Femtosecond laser capsulorrhexis may translate into better predictability in IOL power calculation, with improved refractive outcome predictability.
Purpose: To evaluate the precision of femtosecond laser incisions guided by real time OCT measurements of the cornea iris and capsular bag.
Methods: In 25 eyes in a prospective randomized IRB-approved study, OCT in the femtosecond laser system identified the iris and the anterior and posterior surface of the cornea and capsular bag. The planned position, size, and shape of the capsulotomy, nuclear fragmentation, and clear corneal incisions were adjusted and delivered in reference to the ocular surfaces. Resulting laser incisions were measured.
Results: OCT ocular surface identification guided the femtosecond laser incisions to within 100 µm.
Conclusion: OCT guidance for laser-assisted cataract surgery can increase the accuracy of customized incision placement during cataract surgery.
Purpose: To investigate whether laser lens fragmentation can reduce ultrasound energy during cataract surgery.
Methods: A prospective, open-label study tested 3 algorithms. Eighty-seven subjects were in the fragmentation group, and 32 in the nonfragmentation group. Comparisons of the phaco energy (cumulated dissipated energy, or CDE) were made.
Results: Mean CDE in the fragmented group was 12.9 ± 15.8 and 21.6 ± 15.8 for the controls. The best algorithm values were 0.7 ± 0.9 for Grade 1, 0.9 ± 1.6 for Grade 2, 5.6 ± 4.4 for Grade 3, and 18.9 ± 13.3 for Grade 4. In the control group, values were 9.0 ± 6.9, 18.4 ± 6.4, 21.0 ± 11.2, and 33.0 ± 24.8, respectively.
Conclusion: Lens fragmentation prior to cataract extraction significantly reduced the amount of ultrasound energy required to remove up to Grade 4 cataract. Choice of cutting pattern maximizes these benefits.
Purpose: To compare the size and shape accuracy of a capsulotomy performed by a femtosecond laser with conventional manual methods.
Methods: Twenty-five patients were bilaterally treated with a femtosecond laser–based capsulotomy and surgical continuous curvilinear capsulorrhexis targeting a circular capsular aperture 5 mm in diameter. Excised capsular tissue was analyzed for size and deviation from a perfect circle.
Results: In comparison to manual technique, the measured diameter following femtosecond laser capsulotomy was an order of magnitude more accurate, with fewer tags, radial tears, appendages, and irregularities.
Conclusion: The Optimedica femtosecond laser–performed capsulotomy was more predictable in size and shape compared to manual technique.
Purpose: To manufacture customized IOLs using high repetition rate–focused femtosecond laser pulses.
Methods: Focused femtosecond laser pulses can increase the refractive index of the lens material by approximately 1%. Different patterns of refractive index modifications can provide selected dioptic power toric adjustment and/or aspheric adjustment.
Results: Several IOLs have been manufactured using a standard polymeric material. In a lens button with 6-mm diameter, in a 50-µm anterior layer, a dioptic power of 20 D was created using 200 zones, based on a phase wrapping algorithm.
Conclusion: Results suggest that customized IOLs can be generated with focused femtosecond laser pulses.
Purpose: To compare the safety and efficacy of refractive cataract surgery with accommodating IOL implantation using an image-guided femtosecond laser.
Methods: Fifty eyes undergoing refractive cataract surgery with an accommodating IOL had cataract surgery performed with the femtosecond laser, including the incisions capsulotomy and nucleus cracking or softening. A presbyopia-correcting, accommodating IOL was subsequently implanted, and standard outcome measures were taken postoperatively.
Results: Standard outcome metrics were superior in the femtosecond laser group compared to other published non-femtosecond laser series.
Conclusion: A femtosecond laser may improve safety and efficacy in refractive cataract surgery.
Purpose: Laser lens fragmentation reduces the need for ultrasound energy during cataract surgery. Surgeon feedback can identify the effectiveness of the patterns cut.
Methods: A single surgeon evaluated the effectiveness of 3 fragmentation algorithms.
Results: One algorithm was better on all parameters evaluated. The preferred algorithm allowed hydrodissection through the fragmentation pattern in 80% of cases, accommodated the prechopper in 86% of cases, allowed removal of the nucleus without phaco-grooving in 80% of cases, and made the lens easier to remove in 80% of cases.
Conclusion: Surgeon feedback can direct the selection of fragmentation algorithms and can be compared to the cumulated dissipated energy reductions as a further check of algorithm effectiveness.