Steven E. Wilson, MD
Cleveland
I AM ONE OF MANY SURGEONS who've been using the femtosecond laser and striving to find its role in the care of refractive surgery patients in my practice. For more than three months, I switched almost exclusively to using the femtosecond laser to prepare LASIK flaps. After identifying both clinical and histopathological treatment issues, along with a notable slowdown in my surgery schedule when more than a few femtosecond laser cases are included, I'm now recommending femtosecond laser flaps only for patients who have specific clinical indications for this technology. These include: eyes in which the cornea is too thin for the intended level of correction with a potentially thicker flap prepared with a microkeratome; corneas that have mean corneal curvature greater than 48 D or lower than 42 D, where flap complications are more likely with a microkeratome (buttonhole flaps, small diameter flaps, and so on); and corneas with anterior basement membrane dystrophy. I've found that these situations now account for approximately 25 to 30 percent of my cases.
Early Inflammation, Impact on Cells
The biggest reason for my reluctance to use the femtosecond laser for all LASIK flaps is the obviously greater inflammation noted in the early postoperative period, resulting in slower visual recovery, even if eyes are treated with a potent corticosteroid such as prednisolone acetate 1% every hour beginning immediately after use of the femtosecond laser.
In my experience, some eyes will develop significant central diffuse lamellar keratitis if this intensive corticosteroid regimen is not used. Based on corneal wound healing research performed in my laboratory (Netto MV, Wilson SE, Dupps WJ, Mohan RR, Krueger RR, American Society of Cataract and Refractive Surgery Annual Meeting, Washington D.C., April 2005), including comparisons of the cellular responses with the Intralase (Irvine, CA) femtosecond laser compared to the Hansatome (Bausch & Lomb) microkeratome, this is likely due to greater epithelial injury or cell death produced at the flap edge with the femtosecond laser than with the Hansatome.
The greater the side cut energy used, the greater the number of epithelial cells injured or killed by the femtosecond laser. There is a vast literature, including our own basic research, showing that the normal uninjured epithelium is filled of pro-inflammatory cytokines like interleukin-1 and tumor necrosis factor alpha that only get out of the epithelial cells in significant amounts when the cells are damaged.1-3 When a large number of these epithelial cells are damaged, the released cytokines attract inflammatory cells into the cornea—both directly and by stimulating keratocytes to markedly up-regulate their production of pro-inflammatory chemokines that also attract inflammatory cells into the stroma. These are the normal pathways for a cornea to respond to the perils of an epithelial injury (for example, the onset of a herpes virus or adenovirus infection) and are markedly greater after LASIK flap formation with the femtosecond laser than with the microkeratome. Thus, immunohistological staining for specific inflammatory cells shows conclusively more monocytes in the cornea after formation of flaps with a femtosecond laser than with a microkeratome.
When side cut energies are decreased, there is less epithelial injury and lower release of these proinflammatory cytokines and inflammation. The release of these pro-inflammatory modulators, however, and the tendency towards inflammation will always be greater with the femtosecond laser than microkeratomes with a sharp blade, unless the epithelial injury produced by the femtosecond laser can be markedly reduced.
This epithelial injury difference is best seen with the scanning electron microscope, but can be easily confirmed by any surgeon at the operating microscope. The surgeon must use a spatula or other tool to locate the edge of the flap after use of a microkeratome, but a groove of epithelial injury is obvious after use of the femtosecond laser.
In my experience, if the femtosecond laser side cut energy is lowered to less than 2.0 mJ, I begin having difficulty lifting the flap in some eyes. If it's lowered to less than 1.7 mJ, I frequently cannot lift the flap at all, although I still see the groove at the operating microscope. My colleagues and I have tried many different combinations of stromal cut energy and side cut energy with the femtosecond laser and we have not been able to reduce the parameters to a level at which inflammation is negligible without having significant flap lifting difficulties. While efforts to make the stromal cut smoother by increasing parameters such as spot density and laser speed will be helpful to create smoother stromal beds, efforts should also be made to reduce epithelial injury by altering the configuration of the side cut where it progresses through the epithelium.
Our studies also show large differences in the number of TUNEL-positive keratocytes along the anterior and posterior lamellar interface at four hours following Intralase laser flap formation compared with microkeratome flap formation. The TUNEL assay is designed to stain cells that are undergoing programmed cell death (apoptosis), but under certain circumstances can also detect cells undergoing necrosis. In any case, a lot more keratocytes die in the stroma above and below the interface after femtosecond laser surgery, and this leads to greater proliferation of residual keratocytes detected by immunohistological staining for mitosis markers. Correspondingly greater numbers of activated keratocytes can be seen at the slit lamp in many patient corneas for weeks or months after surgery. These prominent cells will likely disappear with longer follow-up, but they could be a source of mild glare during the first year or so after femtosecond LASIK.
Flap Design
In defense of the femtosecond laser, our histopathological studies demonstrate that the laser does indeed provide a more planar flap than the Hansatome microkeratome. Intralase Corp. hypothesizes that this flap configuration is better for custom corneal ablation. However, I'm aware of no peer-reviewed data to support this hypothesis, and I remain skeptical that a difference can be demonstrated in the clinical results of LASIK with custom corneal ablation obtained with the femtosecond laser flaps compared with microkeratome flaps.
In the past year and a half, I've had only a single Hansatome flap-cutting complication—an irregular flap—when using the patient guidelines I mentioned above. In contrast, I've had four Intralase flap complications—a superiorly decentered flap, two losses of suction in the middle of the stromal pass, and a very thin flap when attempting to cut a 110-µm flap. The only significant complication was in the eye with the thin flap. When I attempted to cut an even deeper flap (180 µm) three months later, again with the femtosecond laser, another very thin flap was produced and could not be lifted. This patient will likely need transepithelial PRK with mytomycin.
Light Sensitivity
I've also had two patients with severe "good vision photosensitivity syndrome" (GAP) or "transient light sensitivity syndrome" (TLS). Both patients underwent a 10-day course of 1% prednisolone acetate beginning with one drop every hour. One patient was effectively treated, but the other noted disappearance of her symptoms for only about a month before she had a recurrence of the severe photosensitivity without slit-lamp signs of inflammation. I then treated her with a three-week 1% prednisolone acetate taper plus a one-week Medrol oral steroid pack and her symptoms have not recurred. I believe GAP or TLS is likely an inflammation in the ciliary body or other posterior structures related to formation of the pocket with the femtosecond laser since corticosteroids have been shown to have little, if any, effect on activated keratocytes or myofibroblasts.
The Bottom Line
The corneal biology of the situation is very clear and, unfortunately, the femtosecond laser is caught between a rock and a hard place. Increase the side cut energy and you get flaps that are easier to lift, but more inflammation from activation of the normal corneal systems involving epithelial-stromal-inflammatory cell interactions; decrease the energy and you get less inflammation, but increased difficulty raising the flaps.
I guess my approach to the femtosecond laser vs. the microkeratome in LASIK comes down to a simple question. Why would I want to have more patients than necessary that take longer for surgery and have a slower visual recovery with more inflammation (that could also rarely develop TLS)? Some patients, however, definitely benefit from femtosecond laser flap formation. Therefore, the instrument is a critical addition to the armamentarium of any refractive surgery practice. I believe my approach to integrating both the microkeratome and femtosecond laser into LASIK surgery is optimizing surgery flow, while at the same time providing the best procedure for each patient.
Dr. Wilson is director of corneal research, and staff refractive and corneal surgeon at the Cole Eye Institute, the Cleveland Clinic Foundation. He has no commercial or proprietary interest in any microkeratome or the femtosecond laser.
1. Hong J-W, Liu JJ, Lee J-S, Mohan RR, et al. Pro-inflammatory chemokine induction in keratocytes and inflammatory cell infiltration into the cornea. Invest Ophthalmol Vis Sci 2001;42:2795-2803.
2. Wilson SE. Mohan RR, Mohan RR, Ambrósio R Jr, et al. The corneal wound healing response: Cytokine-mediated interaction of the epithelium, stroma, and inflammatory cells. Prog Retin Eye Res 2001;20:625-37.
3. Mohan RR, Hutcheon AEK, Choi R, Hong J-W, et al. Apoptosis, necrosis, proliferation, and myofibroblast generation in the stroma following LASIK and PRK. Exp Eye Res 2003;76:71-87 and Wilson SE, Netto M, Ambrosio R, Jr. Corneal cells: Chatty in development, homeostasis, wound healing, and disease. Am J Ophthalmol 2003;136:530-536.
Femtosecond Laser vs. Microkeratome LASIK Flaps
The keys to femtosecond laser use in my practice are safety and accuracy: 95 percent of my flaps are made with the laser.
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I ALSO USE BOTH THE FEMTOSECond laser and blade microkeratome technology to create flaps. I am comfortable with both technologies having used microkeratome technology for more than 12 years and femtosecond laser technology for three-and-a-half years.
Safety First
I initially acquired the femtosecond laser technology were for safety reasons. Even though I have had a lot of success with blade flaps, I have also been through partial flaps, free caps, button holes, and very thin irregular flaps.1 My goal was to lessen the chance of these troublesome complications.
The majority of these blade flap complication cases have regained reasonable best corrected Snellen chart vision. When one puts a complication like this to the test of patient symptoms, however, it is rare to talk to a patient who feels the complication eye sees as crisply as the uncomplicated eye in low light. This is often confirmed with wavefront technology by more high-order aberrations induced in the complication eye. That is why when a surgeon reports that 20/20 vision was maintained after a buttonhole or irregular flap with blade technology, I like to know the patient's low-light visual symptoms and his wavefront measurement also. I see folks referred to me for blade flap complications repair, and a lot of them may still have 20/20 best corrected vision but are not happy with their best corrected image quality. Thus my philosophy is to try to minimize the risk of stromal flap complications, and since it is well known that partial flaps, button holes, and irregular flaps are more common with blade flap technology, I feel that every LASIK surgeon's patients can benefit by being given the option of laser flap technology.1
I have now made more than 5,000 laser flaps with not one button hole, partial flap or irregular flap. I have lost suction now four times, and each time I simply regained suction and finished the case without incident. If I do lose suction though, I want to regain suction within the next few minutes and finish the case.
We need to remember that even though femtosecond technology is very accurate it is also surgeon-dependent. The only way to get a thin irregular flap is if there is not adequate suction. But if the surgeon concentrates on applanation of the focusing lens to the cornea, a quality flap should occur in every situation. Dr. Wilson talks about a thin flap he achieved going for a 110-µm flap. I suspect adequate suction and applanation were not obtained. I use 100-µm flaps on every case and have never had a partial or irregular flap. Dr. Wilson talks about re-cutting with the femtosecond laser after his flap complication and how this did not go so well. I would not recommend re-cutting a cornea with a previous lamellar flap, if at all possible. If you use the femtosecond laser to re-cut a cornea with an established lamellar plane, the laser byproducts of CO2 and water want to follow the path of least resistance, which is the initial lamellar plane. This is not a wise maneuver. Even if a clean uncomplicated new lamellar plane were created without the gases going into the initial plane, the dissection of a laser flap takes a bit more manipulation than a blade flap. This manipulation could also disrupt the bridge of tissue that is now between two planes. This is not a good use for the femtosecond laser in my opinion. That is why I tell patients with blade flap complications that if they want more surgery it is going to either be with the same technology that they had the initial complication with—the blade flap—or a PRK procedure with its subsequent increased risk of haze in an eye with previous surgery.2
Light Sensitivity
I agree that is important for surgeons and patients to know that some patients can have transient light sensitivity after laser flap creation. I find it is most common in the first three months. It is rare for it to be severe, but is treatable. I treat these patients with topical steroids q.i.d. for one week. This is typically all it takes. If it recurs it is usually due to dry eye or meibomitis, and these are treated appropriately. It is important for surgeons looking into adding laser flap technology to their practice to realize that most patients do not have to deal with this issue. It is also well-known to corneal surgeons that anytime we incise a cornea with blade flap LASIK3 or radial/astigmatic keratotomy,4 there is the risk of transient, and rarely permanent light sensitivity.
It is of note that I treat my laser and blade flap patients with the same drop regime. I do not use preoperative drops for either situation. Postoperatively I use topical 1% prednisolone q.i.d. for one week, b.i.d. for the next week, and then discontinue steroid drops. I use the antibiotic drops q.i.d. for one week.
I feel that an important surgeon-dependent issue with laser flaps is the management of the intrastromal bubbles of CO2 and water. If too-aggressive applanation is used, the gases want to dissect into the flap or the bed. My goal is for these bubbles to escape to the limbus. That is why I like softer applanation, and I adjust the suction ring so that the meniscus is near the hinge. The hinge is where the ablation begins, and if the meniscus is near the hinge, the initial bubbles created want to escape to the path of least resistance (the limbus). By using this technique the ablations are smoother, and the day one visions sharper. Feel free to e-mail me if you would like further explanation of this technique.
Flap Issues
I have seen late flap displacement and dehiscence with trauma years later after blade flap creation. I have lifted blade flaps eight years later that were very easy to lift. I have never felt much of an adhesion when lifting blade flaps except at the edge. In contrast, I and many other surgeons have been impressed with the increase in the healing response and adhesion at the interface in laser flaps. This is felt to be a positive and I applaud Dr. Wilson's research in showing us why this adhesion occurs and the details of the healing response. I consider this a positive healing response that leaves a laser flap patient less susceptible to flap trauma in the long run when compared to blade flap patients.
As far as flap centration, whether one is creating a blade or a laser flap, this is another surgeon-dependent issue. It is not the laser's fault if the surgeon lines the applanation lens up in a de-centered fashion and still chooses to depress the foot pedal and deliver the laser energy. If I am ever in question of centration I stop, mark the center of the pupil with a light dye mark, and then re-center the suction ring. But again, centration is a surgeon-dependent issue.
Even though I feel the number of patients a doctor can do in an hour should not be a deciding factor over patient safety, I would like to address this issue since it has been brought up. In my practice I do 16 bilateral laser flap LASIK on a typical surgery day. This is the volume we were doing of blade flaps before introducing Intralase technology to my practice. Right after I received my Intralase laser, I scheduled 12 cases in day as I got used to it, but within six weeks we were back to our 16 cases in a day. I know other surgeons who are using their laser flap technology at even higher volume levels in a day. This technology does not have to slow you down. My staff loves laser flap technology because there is much less hassle for them in turnover and preparation when compared to microkeratome technology.
Blade and laser flaps can both create nice flaps. The reason that more than 95 percent of the flaps made in my practice are with the laser is that it is safer with less risk of a partial flap or a hole in the flap. The other reason is that it is more accurate.5 We feel this is because of the planar flap and the fact that fluid and debris are not dragged into the interface as with blade flaps. This makes for a more controlled environment for stromal hydration in laser flaps. Whatever the reason, a number studies have shown the increase accuracy of final vision outcome of laser flap LASIK over blade flap LASIK.6,7 It has also been shown that there is less induction of high-order aberrations with laser flaps when compared to blade flaps.8,9
Again, I offer both technologies in my practice. With a focus on the steps that are surgeon-dependent with laser flap technology, this is a revolutionary technology with a level of safety and accuracy that many patients have been waiting for.
Dr. Thompson practices at Vance Thompson Vision/ Sioux Valley Clinic. He is also an assistant professor of ophthalmology at the University of South Dakota School of Medicine.
1. Nakano K, Nakano E, Oliveira M, et al. Intraoperative microkeratome complications in 47,094 laser in situ keratomileusis surgeries. J Refract Surg. 2004 Sep-Oct;20(5 Suppl):S723-6.
2. Shaikh N, Wee C, Kaufman S. The safety and efficacy of photorefractive keratectomy after laser in situ keratomileusis. J Refract Surg 2005;21:353-8.
3. Hill J. An informal satisfaction survey of 200 patients after laser in situ keratomileusis. J Refract Surg 2002;18:454-9.
4, Rashid ER, Waring GO 3rd. Complications of radial and transverse keratotomy. Surv Ophthalmol 1989;34:73-106.
5. Binder P: Flap dimensions created with the IntraLase FS laser. J Cataract Refract Surg 2004;30:26-32.
6. Kezirian GM, Stonecipher KG. Comparison of the IntraLase femtosecond laser and mechanical keratomes for laser in situ keratomileusis. J Cataract Refract Surg 2004;30:804-11.
7. Touboul D, Salin F, Mortemousque B, et al. Advantages and disadvantages of the femtosecond laser microkeratome. J Fr Ophtalmol 2005;28:535-46.
8. Tran DB, Sarayba MA, Bor Z, et al. Randomized prospective clinical study comparing induced aberrations with IntraLase and Hansatome flap creation in fellow eyes: potential impact on wavefront-guided laser in situ keratomileusis. J Cataract Refract Surg 2005;31:97-105.
9. Durrie DS, Kezirian GM: Femtosecond laser versus mechanical keratome flaps in wavefront-guided laser in situ keratomileusis: prospective contralateral eye study. J Cataract Refract Surg 2005;31:120-6.
