Peer-Reviewed Literature: Femtosecond Laser Versus Microkeratome-Assisted LASIK
Editor: Ming Wang, MD, PhD
Co-Editor: Tracy Swartz, OD, MS
Reviewer: Paul Sanghera, MD,
Panel Members: Helen Boerman, OD; Y. Ralph Chu, MD; Khalid Hasanee, MD; Wei Jiang, MD; Baseer Khan, MD; Gregory J. McCormick, MD; Jason Noble, BSc, MD; Lav Panchal, MD; Jay S. Pepose, MD, PhD; Jeffrey Sonsino, OD; Renée Solomon, MD

LASIK has become the most common refractive procedure for correcting ametropia. Over the years, the mechanical microkeratome used in the procedure has become the method of choice for creating a central corneal flap. Although rare, flap-related complications induced by the microkeratome often result in undesirable visual consequences. The femtosecond laser, introduced as an alternative to a mechanical keratome, may eliminate complications such as buttonholes, free caps, and decentered flaps. Additionally, several theoretical advantages such as customized lamellar flaps with peripheral angulation may improve healing and prevent epithelial ingrowth and infection. What are the actual anatomical and functional differences between the corneal flaps created by the two modalities? The following articles were reviewed:

1. Sonigo B, Iordanidou V, Chong-Sit D, et al. In vivo corneal confocal microscopy comparison of Intralase femtosecond laser and mechanical microkeratome for laser in situ keratomileusis. Invest Ophthalmol Vis Sci. 2006;47:2803-2811.
2. Kezirian GM, Stonecipher KG. Comparison of the Intralase femtosecond laser and mechanical keratomes for laser in situ keratomileusis. J Cataract Refract Surg. 2004;30:804-811.
3. 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;31:120-126.
4. Lim T, Yang S, Kim M, et al. Comparison of the Intralase femtosecond laser and mechanical microkeratome for laser in situ keratomileusis. Am J Ophthalmol. 2006;141:833-839.

FEMTOSECOND LASER VERSUS MECHANICAL MICROKERATOME
Anatomical Difference in Corneal Flaps
With most microkeratomes, a suction ring positioned around the eye flattens the central cornea so that the microkeratome may cut uniformly. The microkeratome then mechanically creates a lamellar flap of a predetermined thickness. Conversely, the femtosecond laser uses energy in the infrared wavelength in short bursts (one quadrillionth of a second) to produce corneal photodisruption. Plasma forms and thus creates cleavage planes within the corneal stroma that consist of bubbles of carbon dioxide and water.

In a case-controlled study of 44 eyes undergoing LASIK surgery, Sonigo et al¹ used a new-generation Heidelberg Retina Tomograph II/Cornea Module confocal microscope (Heidelberg Engineering GmbH, Dossenheim, Germany) to examine 24 corneal flaps created by the femtosecond laser and 20 corneal flaps created by the Hansatome microkeratome (Bausch & Lomb, Rochester, NY). All patients underwent a single, uneventful surgery without complications. The patients in both groups were matched in terms of demographics, preoperative refraction, and pachymetry. The only difference between the two groups was that the corneal flaps on the femtosecond laser-treated eyes were approximately 50 to 60µm thinner than those made with the mechanical microkeratome. All subjects underwent photoablation by the same excimer laser. Approximately one-half of all patients completed confocal scanning microscopy on regularly scheduled follow-up appointments until 12 months postoperatively.

Investigators found no difference between the two groups in terms of epithelial changes, nerve fiber regeneration in the subbasal region, and the stroma during the follow-up period. In the stroma adjacent to the posterior aspect of the flap in the femtosecond laser patients, investigators saw small hyperreflective areas that likely corresponded to the femtosecond laser's areas of impact. They disappeared within 2 months postoperatively. The examiners also found no incidence of keratocyte-free zones (indicative of apoptosis) in any of the patients and no differences in keratocyte activation between the two groups.

The only observable dissimilarity between the two groups was noted when the investigators imaged the flap's periphery. At 7 days postoperatively, the periphery of the femtosecond laser-created flaps was better defined. At 2 months postoperatively, the edges of the flaps in the femtosecond group were more visible and had hyperreflective, irregularly arranged fibrils indicating a stronger wound healing response than seen in the flaps created with the microkeratome. At 6 and 12 months postoperatively, healing at the flaps' edges seemed to continue in the femtosecond group, with cicatricial fibrotic tissue replacing all of the remaining epithelial plugs. In contrast, microkeratome-created flaps had minimal cicatricial changes during follow-up, and three of 10 eyes examined at 12 months still had evidence of epithelial cells present at the flaps' edges.

The investigators suggested that the greater cicatricial changes at the flaps' edges at 12 months postoperatively in patients undergoing femtosecond laser-assisted LASIK might produce stronger flap adhesion, a theory that must be verified by more thorough studies.

Functional Differences in Corneal Flaps
There are relatively few studies in the literature that have directly compared the functional outcomes of both femtosecond-assisted LASIK and microkeratome-assisted LASIK. The earliest comparison was a retrospective analysis by Kezirian and Stonecipher,² in which they analyzed the LASIK outcomes of one surgeon. The enrollment criteria for patients in that study included a preoperative manifest spherocylindrical equivalent of between -1.00 and -7.00D, preoperative manifest astigmatism of between 0 and 4.00D, and a BSCVA of 20/20 or better. Prior to the end of 2002, the surgeon had used a Hansatome microkeratome on 143 eyes and a CB microkeratome (Moria, Antony, France) on 126 eyes. After 2002, the surgeon switched to the femtosecond laser, and 106 eligible eyes were included in the analysis.

The thickness of the flap was set at 130µm for both the CB microkeratome and the femtosecond laser and at 180µm for the Hansatome microkeratome. The investigators discovered that the femtosecond laser's flaps were significantly thinner and less varied in their thickness than those of the two microkeratomes (P<.001). The UCVA in all groups was similar on postoperative day 1. The UCVA and BSCVA at 3 months postoperatively were not statistically different between the three groups. More patients achieved a manifest spherocylindrical equivalent of ±0.50D with femtosecond-assisted LASIK than with either the CB or Hansatome microkeratome (91% vs 73% and 74%, respectively). Moreover, the investigators found that, although the mean level of postoperative astigmatism was similar in all groups, femtosecond laser-assisted LASIK more accurately and reproducibly corrected astigmatism (P<.01, F test for variance).

In a prospective, contralateral eye study of wavefront-guided LASIK comparing flaps created with either the femtosecond laser or the Hansatome microkeratome, Kezirian and Durrie³ reported improved refractive outcomes and astigmatic neutrality in the femtosecond group. Fifty-one consecutive patients were enrolled.

Preoperatively, patients had manifest myopia of up to -7.00D of sphere with less than -0.50D of astigmatism in either eye, or an aberrometer-dilated refraction of less than -7.00D of sphere with less than -1.50D of astigmatism in either eye.

Patients were randomized to receive a corneal flap created by the femtosecond laser on one eye and one created by the Hansatome microkeratome in their fellow eye. The femtosecond laser was set for a 118-µm thick flap with a 55° hinge and 65° side-cut angle, with a diameter of 9mm. Flaps created with the Hansatome had a superior hinge, were 180µm thick, and were made using a 9.5-mm suction head. LASIK procedures in both groups were performed using the same excimer laser.

The mean UCVA in the femtosecond group was significantly better than in the Hansatome group for all follow-up periods from 1 day to 3 months postoperatively. In addition, more eyes achieved a UCVA of 20/20 and 20/16 in the femtosecond group (P<.03 and P<.05, respectively). Eyes in the femtosecond group were more likely to achieve an MSRE of ±0.50D at 1 week and 1 month postoperatively. This difference between the two groups disappeared at 3 months.

The mean astigmatic results were better in the femtosecond eyes at all postoperative intervals (P<.01). The Hansatome eyes had significantly higher aberrometry readings with RMS astigmatism and oblique trefoil aberrations. The investigators found that it was not manifest but rather secondary astigmatism as well as trefoil that correlated with poorer refractive outcomes postoperatively. Kezirian and Durrie concluded that the corneal flaps created by the femtosecond laser might experience fewer second- and third-degree aberrations postoperatively, thus resulting in better refractive outcomes.

Another study, however, is not supportive of a significant functional difference between femtosecond- and microkeratome-assisted LASIK. Lim et al⁴ studied the clinical outcomes in 55 eyes of 30 patients in a nonrandomized clinical trial where patients were given the choice of method for creating their corneal flap. There were no preoperative refractive exclusion criteria. The Hansatome microkeratome was used in 27 eyes of 16 patients and the femtosecond in 28 eyes of 14 patients. Unlike the studies mentioned earlier, Lim et al found no significant differences between the two groups in terms of postoperative visual acuities, refractions, or higher-order aberrations except for a higher amount of spherical aberration in the microkeratome group (P<.5). The eyes treated with the femtosecond laser also had statistically significant improvements in mesopic, high-frequency contrast sensitivity and the length of time required for corneal sensation to return. The investigators concluded that a larger, randomized study is warranted to assess for differences between the two groups and associated visual improvements postoperatively.

THE BOTTOM LINE
For refractive surgery, femtosecond laser-assisted corneal flaps are anatomically different and may result in different functional outcomes than microkeratome flaps. Femtosecond flaps seem to have greater peripheral wound healing, which may lead to a more adherent flap.

Dissension exists in the literature regarding whether the femtosecond laser's flaps are associated with fewer postoperative lower-order aberrations and possibly improve visual outcomes. A larger randomized study is warranted to verify whether differences actually lead to improved short- and long-term visual outcomes.

Reviewer
Dr. Sanghera acknowledged no financial interest in the products or companies mentioned herein. He may be reached at (416) 666-7115; sanghera@rogers.com.

Panel Members
Helen Boerman, OD, is Assistant Clinical Operations Manager at the Wang Vision Institute in Nashville, Tennessee, and Staff Optometrist, Adjunct Faculty, Indiana University School of Optometry in Bloomington. She acknowledged no financial interest in the products or companies mentioned herein. Dr. Boerman may be reached at (615) 321-8881; drboerman@wangvisioninstitute.com.
Y. Ralph Chu, MD, is Medical Director, Chu Vision Institute in Edina, Minnesota. He acknowledged no financial interest in the products or companies mentioned herein. Dr. Chu may be reached at (952) 835-1235; yrchu@chuvision.com.
Khalid Hasanee, MD, is a fellow of glaucoma and anterior segment at the University of Toronto. He acknowledged no financial interest in the products or companies mentioned herein. Dr. Hasanee may be reached at (416) 500-3937; khalidhasanee@hotmail.com.
Wei Jiang, MD, is general ophthalmologist practicing in Kaiser, California. She acknowledged no financial interest in the products or companies mentioned herein. Dr. Jiang may be reached at (925) 847-5065; wjiang70@yahoo.com.
Baseer Khan, MD, is a fellow of glaucoma and anterior segment at the University of Toronto. He acknowledged no financial interest in the products or companies mentioned herein. Dr. Khan may be reached at (415) 258-8211; baseer@eyekhan.ca.
Gregory J. McCormick, MD, is a cornea and refractive fellow at the University of Rochester Eye Institute in New York. He acknowledged no financial interest in the products or companies mentioned herein. Dr. McCormick may be reached at (585) 256-2569; mccormick_greg@hotmail.com.
Jason Noble, BSc, MD, is a resident physician at the Department of Ophthalmology and Vision Sciences at the University of Toronto. He acknowledged no financial interest in the products or companies mentioned herein. Dr. Noble may be reached at (416) 844-5477; jason.noble@utoronto.ca.
Lav Panchal, MD, is Clinical Instructor in the Ophthalmology Department at the University of Tennessee and a cornea and refractive surgeon at the Wang Vision Institute in Nashville, Tennessee. He acknowledged no financial interest in the products or companies mentioned herein.Dr. Panchal may be reached at (917) 751-8651; drpanchal@wangvisioninstitute.com.
Jay S. Pepose, MD, PhD, is Professor of Clinical Ophthalmology & Visual Sciences, Washington University School of Medicine, St. Louis. He acknowledged no financial interest in the products or companies mentioned herein. Dr. Pepose may be reached at (636) 728-0111; jpepose@peposevision.com.
Jeffrey Sonsino, OD, is a faculty member at the Vanderbilt Eye Institute in Nashville, Tennessee. He acknowledged no financial interest in the products or companies mentioned herein. Dr. Sonsino may be reached at (615) 936-1328; jeffrey.sonsino@vanderbilt.edu.
Renée Solomon, MD, is an ophthalmology fellow at Ophthalmic Consultants of Long Island in New York. She acknowledged no financial interest in the products or companies mentioned herein. Dr. Solomon may be reached at reneeoph@yahoo.com.

Editor
Ming Wang, MD, PhD, Clinical Associate Professor of Ophthalmology at the University of Tennessee and Director of the Wang Vision Institute in Nashville, Tennessee. Dr. Wang acknowledged no financial interest in the products or companies mentioned herein. He may be reached at (615) 321-8881; drwang@wangvisioninstitute.com.

Co-Editor
Tracy Swartz, OD, Educational Director at the Wang Vision Institute in Nashville, Tennessee. Dr. Swartz acknowledged no financial interest in the products or companies mentioned herein. She may be reached at (615) 321-8881; drswartz@wangvisioninstitute.com.