Flap Thickness Variability: A Comparative Study

The advent of femtosecond laser LASIK flap creation in 2001 marked a paradigm shift in refractive surgery, providing surgeons with a way to create a more precise corneal flap,¹ cause less ocular tissue damage,² and still achieve the same reproducible surgical outcomes as with a mechanical microkeratome. ³ With a variety of femtosecond laser models available to us—many of which are second-, third-, fourth-, or even fifth-generation systems—we can now produce increasingly precise, regular, and thinner cuts and decrease the rate of flap-related complications.

Recently, we conducted an investigation using a latestgeneration femtosecond laser, an earlier femtosecond laser model, and a mechanical microkeratome to determine which platform produced the least variability in flap thickness.

BACKGROUND

A large body of evidence supports the advantages of flap creation with a femtosecond laser versus a mechanical microkeratome.^1,2,4-13 Of particular interest, Gil-Cazorla et al⁴ showed that refractive results were better after hyperopic LASIK in patients whose flaps were created with a femtosecond laser. Kamburoglu et al5 determined that femtosecond LASIK was associated with fewer cases of clinically significant postoperative epithelial ingrowth than LASIK with a mechanical microkeratome. Furthermore, comparisons of flap characteristics including morphology, cut accuracy, stromal bed surface roughness, histopathology, flap edge quality, and flap thickness reproducibility favor outcomes with the femtosecond laser.^6-13

Flap thickness reproducibility is especially important, as any refractive cut in the cornea should preserve as much stromal bed as possible. Excessively thick flaps can compromise biomechanical corneal strength and lead to iatrogenic corneal ectasia.¹⁴ Therefore, achieving a thin flap can potentially enhance postoperative outcomes. Adequate residual stromal preservation also avoids cutting corneal nerves, thereby reducing the incidence of postoperative dry eye symptoms.¹⁵ Unfortunately, however, there is such a thing as going too thin, as flaps thinner than 90 μm run the risk of causing flap slippage, LASIK striae, flap irregularities, astigmatism, buttonholes, free caps, and corneal haze.16,17 Any of these complications can delay or compromise visual recovery.

Corneal thickness mapping to obtain postoperative flap thickness measurements can be performed with anterior segment optical coherence tomography (OCT)^18,19 and arc-scanning high-frequency ultrasound biomicroscopy.²⁰ The latter can be used to map the total cornea, epithelium, residual stroma, flap, and flap-stromal composition; the former can distinguish the epithelium and flap interface using high-resolution corneal meridian scans, but it cannot visualize the entire cornea or epithelium nor determine total flap thickness.

Another important consideration for creation of an ideal LASIK flap is residual epithelial thickness, which provides an indication of epithelial activity. The epithelium may grow thicker (ie, epithelial hypertrophy) in the less rigid cornea of an eye after flap creation due to variations in intraocular pressure and flap-interface abnormalities. Therefore, residual epithelial thickness measurements can be helpful to make a differential diagnosis in the instance of myopic regression.^21,22

LOCAL THICKNESS VARIABILITY STUDY

We conducted an interventional case series to determine differences in local flap thickness variability in conjunction with epithelial thickness and local epithelial variability after primary bilateral LASIK. We also investigated possible correlations between flap thickness variability and epithelial hyperplasia and/or variability of epithelial thickness.

Eyes were divided into three groups based on the mode of flap creation: group A had flaps created with the M2 Microkeratome (Moria), group B with the IntraLase FS60 femtosecond laser (Abbott Medical Optics Inc.), and group C with the FS200 femtosecond laser (Alcon). Treatments were performed between January 1999 and February 2012 by the same surgeon (AJK) and correction of between -2.00 and -10.00 D with up to 3.00 D of corneal astigmatism. Eyes included in this series were free of corneal dystrophies, herpetic eye diseases, keratoconus, contact lens warpage, corneal scarring, glaucoma, severe dry eye, and collagen vascular diseases. All patients had a complication-free postoperative recovery.

Flap and epithelial thickness measurements were taken between November 2011 and March 2012; 21 patients were enrolled in group A, 13 in group B, and 20 in group C. Postoperative flap and epithelial thicknesses were measured with the Artemis II+ superior (Artemis Medical Technologies Inc.) at 66.5 ±49.7 months, 42.3 ±14.7 months, and 6.7 ±5.3 months in groups A, B, and C, respectively. Mean thickness measurements were taken for the total (0.0–6.0 mm), central (0.0–3.0 mm), and peripheral (3.0–6.0 mm) cornea, and thickness standard deviation was measured across 21 points on a 6.0-mm diameter corneal area. Mean total (0.0–6.0 mm), central (0.0–3.0 mm), and peripheral (3.0–6.0 mm) flap depth and thickness were also measured. Figure 1 details one patient’s postoperative corneal report of epithelial thickness and flap depth measurements, and Figure 2 details three representative flap thickness maps.

During the procedures, flap thicknesses were targeted at 130, 110 to 130, and 90 to 130 μm in groups A, B, and C, respectively. The targeted flap diameter was between 8.3 and 9.0 mm in group B and 8.0 and 8.5 mm in group C. Angled sidecuts and hinge angles were 90º and 55º, respectively, in group B and 70º and 45º, respectively, in group C. After flap creation, myopic correction was performed with the Allegretto Wave Eye-Q excimer laser (Alcon) in groups A and B and with the EX500 (Alcon) in group C.

RESULTS AND DISCUSSION

Flap thickness. Postoperative flap thickness measurements are detailed in Table 1 and Figure 3. Notably, mean flap thickness was highest in group A (138.33 ±12.38 μm vs 128.46 ±5.72 μm in group B and 122.00 ±5.64 μm in group C). Likewise, the average thickness variability—a metric computed from the standard deviation of values from 21 points measured in the 0.0- to 6.0-mm corneal area of each flap—was also highest in group A (9.73 ±4.93 μm vs 8.48 ±4.23 μm in group B and 4.84 ±1.88 μm in group C).

Our results indicate that each of the three devices produced a flap thickness consistent with the intended thickness. However, not only was there less variation in flap thickness in group C compared with groups A and B, but also flaps were more uniform in this group. Twopaired comparisons between the groups revealed a statistically significant flap thickness difference between groups C and A (P=.004) but not between groups B and C (P=.078 and .095, respectively). The slight increase in flap thickness in group A (8.33 μm) can be attributed to the meniscus-shaped flaps created by the mechanical microkeratome. Additionally, a larger flap thickness range (114–159 μm) in this group indicates a relative discrepancy between the intended and achieved results. Other studies have shown similar findings.²³

Across all groups, flap thickness was most accurately reproducible in the central 1.5-mm radius of the cornea compared with the peripheral 3.0- to 4.0-mm radius (paired t-test; P<.05). Also, patient age, preoperative spherical equivalent, manual keratometry, and preoperative central pachymetry did not affect the achieved flap thickness in any group (Pearson correlations test, P<.05).

It is difficult to explain the differences noted between the two femtosecond lasers in this study; however, we theorize that they are related to the method of gas evacuation during the lamellar separation of the flap (Figure 4). The FS60 creates a vertical pocket within the cornea at the hinge site and directs gas into the pocket. The FS200 starts with a channel that connects the lamellar part of the flap with the corneal surface and the hinge. This channel visibly vents gas bubbles throughout the flap, reducing mechanical powers that can alter flap thickness.

Epithelial thickness. Postoperative epithelial thickness measurements are detailed in Table 2 and Figure 5. Interestingly, groups A and B had similar mean epithelial thicknesses (51.50 ±4.19 μm and 51.54 ±4.16 μm, respectively). In group C, the average postoperative increase in epithelial thickness was statistically significantly smaller (49.53 ±4.28 μm), possibly indicating a relevant reaction of the epithelium to the flap thickness regularity.

The most important finding of our study was that topographical variations in flap thickness were not due to epithelial irregularities. We are now studying epithelial regularity with diffraction measurements (C-quant; Oculus Optikgeräte GmbH) to confirm what we sussuspect: An irregular epithelial surface may affect light diffraction and degrade quality of vision.

CONCLUSION

Of the patients enrolled in our study, there was statistically significantly less variation in flap thickness in those that underwent flap creation with the newergeneration FS200 femtosecond laser compared with those that underwent flap creation with the IntraLase or the M2 microkeratome. Our results also showed that, in conjunction with less flap thickness variation in this group, the average increase in epithelial thickness after treatment was also smaller.

A. John Kanellopoulos, MD, is the Director of the LaserVision.gr Eye Institute in Athens, Greece, and is a Clinical Professor of Ophthalmology at New York University School of Medicine. He is also an Associate Chief Medical Editor of CRST Europe. Dr. Kanellopoulos states that he is a consultant to Alcon/WaveLight and Avedro, Inc. He may be reached at tel: +30 21 07 47 27 77; e-mail: ajkmd@mac.com.

George Asimellis, PhD, is in the clinical research department of the LaserVision.gr Eye Institute in Athens, Greece. He states that he has no financial interest in the products or companies mentioned.

1. Sutton G, Hodge C. Accuracy and precision of LASIK flap thickness using the IntraLase femtosecond laser in 1000 consecutive cases. J Refract Surg. 2008;24:802-806.
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. Zhang ZH, Jin HY, Suo Y, et al. Femtosecond laser versus mechanical microkeratome laser in situ keratomileusis for myopia: Meta-analysis of randomized controlled trials. J Cataract Refract Surg. 2011;37(12):2151-2159.
4. Gil-Cazorla R, Teus MA, de Benito-Llopis L, Mikropoulos DG. Femtosecond laser vs mechanical microkeratome for hyperopic laser in situ keratomileusis. Am J Ophthalmol. 2011;152(1):16-21.
5. Kamburoglu G, Ertan A. Epithelial ingrowth after femtosecond laser-assisted in situ keratomileusis. Cornea. 2008;27(10)1122-1125.
6. Kohnen T, Klaproth OK, Derhartunian V, Kook D. Results of 308 consecutive femtosecond laser cuts for LASIK. [In German.] Ophthalmologe. 2010;107(5):439-445.
7. Heichel J, Hammer T, Sietmann R, Duncker GI, Wilhelm F. Scanning electron microscopic characteristics of lamellar keratotomies using the Femtec femtosecond laser and the Zyoptix XP microkeratome. A comparison of quality. [In German.] Ophthalmologe. 2009;107(4):333-340.
8. Holzer MP, Rabsilber TM, Auffarth GU. Femtosecond laser-assisted corneal flap cuts: Morphology, accuracy, and histopathology. Invest Ophthalmol Vis Sci. 2006;47(7):2828-2831.
9. Kim JY, Kim MJ, Kim TI, Choi HJ, Pak JH, Tchah H. A femtosecond laser creates a stronger flap than a mechanical microkeratome. Invest Ophthalmol Vis Sci. 2006;47:599-604.
10. Montes-Micó R, Rodríguez-Galietero A, Alió JL. Femtosecond laser versus mechanical keratome LASIK for myopia. Ophthalmology. 2007;114:62-68.
11. Ahn H, Kim JK, Kim CK, et al. Comparison of laser in situ keratomileusis flaps created by 3 femtosecond lasers and a microkeratome. J Cataract Refract Surg. 2011;37(2):349-357.
12. Chen S, Feng Y, Stojanovic A, Jankov MR, Wang Q. IntraLase femtosecond laser vs mechanical microkeratomes in LASIK for myopia: A systematic review and meta-analysis. J Refract Surg. 2012;28(1):15-24.
13. Khoramnia R, Salgado JP, Lohmann CP, Kobuch KA, von Mohrenfels CW. Precision, morphology, and histology of cornea flap cuts using a 200-kHz femtosecond laser. Eur J Ophthalmol. 2012;22(2):161-167.
14. Koch DD. The riddle of iatrogenic keratectasia. J Cataract Refract Surg. 1999;25:453-454.
15. Kanellopoulos AJ, Pallikaris IG, Donnenfeld ED. Comparison of corneal sensation following photorefractive keratectomy and laser in situ keratomileusis. J Cataract Refract Surg. 1997;23:34-38.
16. Choudhri SA, Feigenbaum SK, Pepose JS. Factors predictive of LASIK flap thickness with the Hansatome zero compression microkeratome. J Refract Surg. 2005;21:253-259.
17. Hatch BB, Moshirfar M, Ollerton AJ, Sikder S, Mifflin MD. A prospective, contralateral comparison of photorefractive keratectomy (PRK) versus thin-flap LASIK: assessment of visual function. Clin Ophthalmol. 2011;5:451-457.
18. von Jagow B, Kohnen T. Corneal architecture of femtosecond laser and microkeratome flaps imaged by anterior segment optical coherence t
19. omography. J Cataract Refract Surg. 2009;35(1):35-41.
20. Xu Y, Zhou X, Wang L, Xu H. A morphological study of corneal flap after thin-flap laser-assisted in situ keratomileusis by anterior segment optical coherence tomography. J Int Med Res. 2010;38(6):1952-1960.
21. Reinstein DZ, Silverman RH, Coleman DJ. High-frequency ultrasound measurement of the thickness of the corneal epithelium. Refract Corneal Surg. 1993;9:385-387.
22. Spadea L, Fasciani R, Necozione S, Balestrazzi E. Role of the corneal epithelium in refractive changes following laser in situ keratomileusis for high myopia. J Refract Surg. 2000;16:133-139.
23. Reinstein DZ, Ameline B, Puech M, Montefiore G, Laroche L. VHF digital ultrasound three dimensional scanning in the diagnosis of myopic regression after corneal refractive surgery. J Refract Surg. 2005;21:480-484.
24. Lackerbauer CA, Kollias A, Kreutzer TC, Ulbig M, Kampik A, Grueterich M. Amadeus II microkeratome: optimizing microkeratome settings for high flap accuracy using optical low coherence reflectometry. Eur J Ophthalmol. 2010;20(1):41-47.