Corneal collagen crosslinking for ectasia after laser in situ keratomileusis: Long-term results

ARTICLE

Corneal collagen crosslinking for ectasia after laser in situ keratomileusis: Long-term results Aydin Yildirim, MD, Hanefi Cakir, MD, Necip Kara, MD, Hasim Uslu, MD, Bulent Gurler, MD, Engin Bilge Ozgurhan, MD, Hatice Nur Colak, MD

PURPOSE: To report the long-term results of corneal collagen crosslinking (CXL) treatment for post-laser in situ keratomileusis (LASIK) ectasia. SETTINGS: Turkiye Hospital Eye Clinic and Fatih University Medical Faculty, Department of Ophthalmology, Istanbul, Turkey. DESIGN: Retrospective case series study. METHODS: Consecutive patients with ectasia after LASIK were treated with CXL. The main outcome measures were uncorrected (UDVA) and corrected (CDVA) distance visual acuities, spherical and cylindrical refractions, and simulated keratometry (K) values. RESULTS: The study enrolled 20 eyes (14 patients; 7 women) with a mean age of 34.8 years G 6.0 (SD) (range 25 to 45 years) and mean follow-up of 42 months (range 36 to 60 months). The UDVA and CDVA improved significantly, from 0.78 G 0.61 logMAR to 0.53 G 0.36 logMAR (PZ.007) and from 0.27 G 0.23 logMAR to 0.19 G 0.13 logMAR, respectively (P%.028). No eye lost 1 or more Snellen lines of UDVA or CDVA. Although the mean spherical refraction was not significantly different at the last visit (PZ.074), the mean cylindrical refraction decreased significantly (PZ.036). The maximum K value decreased from 46.0 G 4.4 diopters (D) at baseline to 45.6 G 3.8 D at the last visit (PZ.013). By the last visit, the maximum K value decreased (R1.0 D) in 5 eyes and remained stable in 15 eyes. No serious complications occurred. CONCLUSIONS: Corneal collagen crosslinking yielded long-term stability in cases with post-LASIK corneal ectasia without significant side effects. Improvements in visual acuity, cylindrical refraction, and maximum K values occurred. Financial Disclosure: No author has a financial or proprietary interest in any material or method mentioned. J Cataract Refract Surg 2014; 40:1591–1596 Q 2014 ASCRS and ESCRS

Iatrogenic corneal ectasia after laser in situ keratomileusis (LASIK) is a rare but devastating complication of refractive surgery. It is associated with progressive corneal steepening, an increase in myopia and astigmatism, and a decrease in uncorrected and corrected visual acuity.1,2 The possible treatment options for post-LASIK ectasia include medication to reduce intraocular pressure, rigid gas-permeable contact lenses, lamellar or penetrating keratoplasty, and intrastromal corneal ring segment implantation.3–6 Corneal collagen crosslinking (CXL) with riboflavin and ultraviolet-A (UVA) radiation is now being used Q 2014 ASCRS and ESCRS Published by Elsevier Inc.

to treat keratoconus and post-LASIK ectasia; the principal goal of the technique is to stabilize the progression of these corneal diseases.7 In addition to stabilizing the cornea, there is improvement in topographic and visual acuity outcomes.8–15 In previous studies of CXL outcomes,16–19 patients had improvement in corrected distance visual acuity (CDVA), uncorrected distance visual acuity (UDVA), maximum and average keratometry (K) values, several corneal topography indices, and corneal and optical higherorder aberrations. The mean follow-up in most previous studies was 1 year or less. Recently, Richoz et al.16 reported the 0886-3350/$ - see front matter http://dx.doi.org/10.1016/j.jcrs.2014.01.042

1591

1592

CORNEAL CXL FOR POST-LASIK ECTASIA

long-term results of corneal CXL in ectasia after LASIK and after photorefractive keratectomy with a follow-up of up to 62 months (mean 25 months). Our study evaluated the effect of CXL for post-LASIK ectasia over the longest follow-up in the existing literature to date. PATIENTS AND METHODS This was a retrospective study of consecutive patients who were treated with CXL for iatrogenic corneal ectasia after LASIK at the Turkiye Hospital Eye Clinic and Fatih University Medical Faculty, Department of Ophthalmology, between 1999 and 2009. The study was approved by the local institutional review board and adhered to the tenets of the Declaration of Helsinki. All patients provided written informed consent. A diagnosis of corneal ectasia was based on the development of progressive central or inferior corneal steepening, an increase in myopia, an increase in astigmatism, loss of UDVA, and loss of CDVA over the past 6 months.1 Exclusion criteria included a history of corneal surgery other than LASIK, corneal pachymetry less than 400 mm, a maximum K value higher than 60.0 D, central corneal opacity, and pregnancy.

Examination and Study Measurements All patients had a comprehensive ophthalmologic examination including UDVA, CDVA, manifest refraction (sphere and cylinder), slitlamp biomicroscopy, Goldmann tonometry, and fundus evaluation. Central corneal thickness measurement by ultrasound pachymetry (AL-3000, Tomey Corp.) and corneal topography measurements (Orbscan II, Bausch & Lomb, Orbtek, Inc.) were also performed.

Surgical Technique All procedures were performed by 1 or 2 experienced surgeons (A.Y., H.C.) according to the Dresden protocol.7 The patients were treated at an outpatient clinic in an excimer laser room under topical anesthesia. After povidone– iodine (Betadine) was applied and the sterile field set with a blepharostat, the epithelium was mechanically debrided with a Desmarres blade over an 8.0 mm diameter without the use of alcohol. The cornea was saturated with a photosensitizing solution of riboflavin 0.1% with 20.0% dextran T500 (Ricrolin) at an instillation rate of 1 drop per 3 minutes for 30 minutes. The slitlamp of the operative microscope was used to assess the presence of riboflavin in

Submitted: October 2, 2013. Final revision submitted: January 10, 2014. Accepted: January 23, 2014. From the Departments of Ophthalmology, Fatih University Medical Faculty Hospital (Yildirim, Uslu, Gurler, Colak), Gaziantep Sehitkamil State Hospital (Kara), and Beyoglu Eye Education and Research Hospital (Ozgurhan), and Turkiye Hospital Eye Clinic (Cakir), Istanbul, Turkey. Corresponding author: Aydin Yildirim, MD, Fatih University Medical Faculty Hospital, Yalı Mah, Sahilyolu Sk. Number 16, Istanbul, 34844, Turkey. E-mail: [email protected].

the anterior chamber, showing complete impregnation of the cornea that was visible as a yellow flare. Corneal thickness was measured before and after epithelium removal. If the cornea was thinner than 400 mm, hypotonic riboflavin was administered. After verification of the ultraviolet-A (UVA) laser source unit's calibration using a UVA power meter, the corneal collagen was polymerized for 30 minutes (Vega CBM x-linker light-emitting diode [LED]–UVA single 370 nm beam, 3 mW/cm2, 5.4 J/cm2). The UV beam's focus was checked initially with an aiming beam produced by 2 centering LEDs (644 nm). During this second step, riboflavin was instilled regularly to maintain its stromal concentration. After the cornea was rinsed with a balanced salt solution and 1 drop of moxifloxacin was instilled, a bandage contact lens was placed. Postoperative treatment included oral analgesics (paracetamol 500 mg 4 times daily for 3 days), 7 days of topical moxifloxacin drops, and topical ketorolac; this was followed by 7 days of topical dexamethasone treatment. All patients were examined 3 day postoperatively to assess the quality of epithelial healing and the absence of infectious complications and to remove the bandage contact lens.

Main Outcomes Measures and Follow-up The main outcome measures were UDVA, CDVA, spherical and cylindrical refractions, simulated K values (minimum and maximum), and thinnest corneal thickness values. These results were recorded preoperatively; 3, 6, and 12 months postoperatively; and at the last visit.

Statistical Analysis Statistical analysis was performed using SPSS for Windows software (version 16.0, SPSS, Inc.). Normality of all data samples was first checked using the KolmogorovSmirnov test. When parametric analysis was possible, the Student t test for paired data was performed for all parameter comparisons between the preoperative and postoperative examinations. Differences with a P value less than 0.05 were considered statistically significant.

RESULTS The study evaluated 20 eyes of 14 patients (7 men, 7 women). The mean patient age at the time of CXL treatment was 34.8 years G 6.0 (SD) (range 25 to 45 years). The mean follow-up was 42 G 7 months (range 36 to 60 months); the mean time to the last visit was 42 months. Pre-LASIK risk factors included 6 eyes with forme fruste keratoconus, 6 eyes with a steep cornea (O47.0 diopters [D]), 5 eyes with a deep stromal ablation (O75 mm), and 4 eyes with undiagnosed pellucid marginal degeneration. No risk factor was determined in 4 cases. No intraoperative or postoperative complications occurred. Table 1 shows the clinical findings over time. Figure 1 shows the lines of UDVA and CDVA gained or lost at the last visit. The UDVA and CDVA improved or remained stable in all eyes. The mean spherical refraction was not statistically significantly different between preoperatively and

J CATARACT REFRACT SURG - VOL 40, OCTOBER 2014

1593

CORNEAL CXL FOR POST-LASIK ECTASIA

Table 1. Preoperative and postoperative clinical findings. Postoperative Parameter Visual acuity (logMAR) UDVA Mean G SD Range P value* CDVA Mean G SD Range P value* Refraction (D) Sphere Mean G SD Range P value* Cylinder Mean G SD Range P value* Keratometry (D) Kmin Mean G SD Range P value* Kmax Mean G SD Range P value* Corneal thickness (mm) Mean G SD Range P value*

Baseline

3 Months

6 Months

12 Months

Last Visit

0.78 G 0.61 0.05, 1.00 d

0.52 G 0.33 0.05, 1.00 .005†

0.51 G 0.32 0.05, 1.00 .005†

0.50 G 0.31 0.05, 1.00 .004†

0.53 G 0.36 0.05, 1.30 .007†

0.27 G 0.23 0.00, 0.82 d

0.21 G 0.13 0.00, 0.52 .036†

0.20 G 0.13 0.00, 0.52 .048†

0.20 G 0.14 0.00, 0.52 .040†

0.19 G 0.13 0.00, 0.40 .028†

1.35 G 1.74 6.00, 0.00 d

1.18 G 1.69 5.50, 0.00 .255

1.08 G 1.60 5.50, 0.00 .067

1.06 G 1.59 5.50, 0.00 .061

1.05 G 1.58 5.50, 0.00 .074

2.28 G 1.08 5.00, 0.75 d

2.02 G 0.88 4.00, 0.75 .023†

1.95 G 0.80 3.50, 0.75 .032†

1.93 G 0.79 3.50, 0.50 .026†

1.96 G 0.83 3.50, 0.50 .036†

42.8 G 2.9 38.1, 49.5 d

42.6 G 3.4 35.9, 50.5 .254

42.3 G 3.6 35.8, 50.1 .073

42.5 G 3.4 35.9, 49.1 .280

42.3 G 3.4 35.4, 48.0 .056

46.0 G 4.4 36.3, 57.3 d

45.7 G 4.2 37.5, 56.7 .015†

45.6 G 4.2 37.4, 56.5 .004†

45.7 G 4.1 37.2, 55.6 .025†

45.6 G 3.8 37.4, 54.2 .013†

477 G 27 430, 527 d

445 G 25 385, 481 .000†

455 G 24 395, 485 .000†

465 G 23 405, 495 .000†

472 G 25 425, 520 .061

CDVA Z corrected distance visual acuity; Kmax Z maximum keratometry; Kmin Z minimum keratometry; UDVA Z uncorrected distance visual acuity *Paired t test comparing values at baseline with postoperative values † Statistically significant

Figure 1. Change in the UDVA and CDVA Snellen lines between baseline and last visit postoperatively (CDVA Z corrected distance visual acuity; UDVA Z uncorrected distance visual acuity).

any postoperative visit (all PO.05). The mean cylindrical refraction was statistically significantly lower at all postoperative visits than at baseline (all P!.05). Figure 2 shows the change in the spherical refraction, cylindrical refraction, minimum K values, and maximum K values. There was no increase in any of the 4 parameters postoperatively. The minimum K values were not significantly different between baseline and any postoperative visit (all PO.05). The maximum K values were statistically significantly lower at all postoperative visits than at baseline (all P!.05). The thinnest corneal thickness was statistically significantly lower 3 months, 6 months, and 12 months postoperatively than at baseline (all P!.05). There was

J CATARACT REFRACT SURG - VOL 40, OCTOBER 2014

1594

CORNEAL CXL FOR POST-LASIK ECTASIA

Figure 2. Change in refraction and K values between baseline and last visit postoperatively (Kmax Z maximum keratometry; Kmin Z minimum keratometry).

no significant difference in values between the preoperative visit and the last postoperative visit (PO.05) (Table 1). DISCUSSION Corneal collagen CXL is a new surgical procedure that uses a combination of riboflavin eyedrops to saturate the cornea and UVA light, which initiates a chemical reaction that increases the crosslinks in intrafibrillar and interfibrillar collagen fibers, thereby increasing the biomechanical stability of the corneal stroma.20–23 The objective of this procedure is to halt progression of keratoconus, post-LASIK ectasia, and other corneal ectasias, such as pellucid marginal degeneration. In some cases, there has been improvement in visual acuity, a reduction in corneal curvature, and improvement in the patient's quality of life.24 Corneal CXL has proved to be very effective in halting the progression of keratoconus. Over the past 10 years, the use of CXL has shown the potential for slowing or eliminating the progression of keratoconus.7,25 The first report of CXL for keratectasia was published by Kohlhaas et al. in 2005.26 Recently, several studies reported that iatrogenic corneal ectasia was successfully treated by CXL, which indicates that it may be an option for treating progressing iatrogenic corneal ectasia.27–29 The current study evaluated CXL for post-LASIK corneal ectasia and presents findings from the longest follow-up to date (mean 42 months). Visual acuity is one of the most important parameters that reflect the efficacy of CXL treatment. In cases with post-LASIK ectasia, Li et al.30 found a significant improvement in UDVA and CDVA 12 months after CXL compared with preoperative levels. Hersh et al.17 report that in 22 eyes with post-LASIK ectasia, although the UDVA was not significantly different 1 year after CXL, the CDVA had significantly improved. They also found that the UDVA improved by 1 or more Snellen lines in 11 eyes (50%), 4 eyes (18%) lost 1 or more lines,

and 7 eyes (32%) remained stable. The CDVA improved by 1 or more Snellen lines in 10 eyes (45.5%), 2 eyes (9%) lost 1 or more lines, and 10 eyes (45.5%) remained stable. Recently, Richoz et al.16 reported long-term outcomes (mean 25 G 13 months) of CXL treatment for postLASIK ectasia. They observed a significant improvement in CDVA. In their study, the CDVA improved (gain R1 line) in 19 cases and remained stable in 7 patients. No patient lost lines of CDVA. In our study, there was statistically significant improvement in UDVA and CDVA at the last visit. The maximum K value is a key topographic indicator of the success of CXL because it measures, to some extent, the severity of the ectatic change. Previous studies report decreases in the maximum K value of 2.01 D,7 1.90 D,8 1.46 D,14 and 1.42 D12 in keratoconic patients. Hafezi et al.28 found a decrease in maximum K value in patients with post-LASIK ectasia. Hersh et al.17 found an insignificant decrease in the mean maximum K value (1.0 D) between preoperatively and 12 months postoperatively in cases of corneal ectasia. Richoz et al.16 report a maximum K value reduction from 52.8 D to 50.9 D after CXL treatment for post-LASIK ectasia; the mean follow-up was 25 months. In the current study, there was a small but statistically significant decrease (mean 0.4 D) in the maximum K value a mean of 42 months after CXL. At the last visit, the maximum K values decreased in 5 eyes and remained stable in 15 eyes. The cause of this small decrease may be the lower baseline maximum K values (mean 46.0 G 4.4 D) than in previous studies. Previous studies report significant changes in manifest astigmatism of 0.93 D14 and 0.26 D15 after CXL treatment for keratoconus. However, Hersh et al.17 report that the mean manifest astigmatism essentially remained unchanged after CXL. Similarly, in the keratoconus and ectasia subgroups, there were no significant changes in the mean manifest astigmatism. In our study, although the cylindrical refraction decreased significantly after CXL, the decrease in spherical refraction was not significant. Corneal thinning is generally concomitant with the early CXL postoperative course. A previous study31 found that the thinnest pachymetry in 28 eyes with corneal ectasia at 1 year appeared to be slightly, although statistically significantly, thinner than preoperatively.32 This is similar to the results in previous studies.12,14,15,33 In our study, the corneal thickness significantly decreased 3, 6, and 12 months postoperatively. However, it was similar to baseline values at the last visit. The long-term findings in our study show that CXL is effective and safe for patients with post-LASIK ectasia. The UDVA, CDVA, spherical and cylindrical refractions, and K values improved or remained stable in all eyes. The possible complications related to CXL include

J CATARACT REFRACT SURG - VOL 40, OCTOBER 2014

CORNEAL CXL FOR POST-LASIK ECTASIA

keratitis, corneal haze, endothelial cell loss, and failure of treatment.16,34–38 In our study, no serious complications occurred during the follow-up. These promising results may be associated with the baseline characteristics of our patients. Although we did not classify the severity of ectasia, most of our patients had mild or moderate cases. The mean maximum K value (46.0 D) was lower in our study than in previous studies. The maximum K value was lower than 50.0 D in 18 of 20 eyes, and the CDVA was 20/40 or better in 11 eyes. Also, no eye developed corneal haze during the follow-up. In general, temporary stromal haze is seen on clinical examination after CXL.39,40 Raiskup et al.41 found a greater tendency toward stromal haze in patients with more advanced cases. Greenstein et al.42 report that the degree of haze was correlated with poorer UDVA and CDVA, thinner pachymetry, and higher maximum K and mean K values. They also stated that the corneal haze seemed to be worse with thinner corneas and resolved as the cornea thickened. The reason no eye developed corneal haze after CXL may be associated with the corneal thickness values at baseline and during the follow-up. The mean and minimum baseline corneal thicknesses were 477 mm and 430 mm, respectively. Also, during the follow-up, the corneal thickness decreased to a mean of 445 mm at 3 months, which was the lowest mean corneal thickness value during the follow-up. Although this study reports the results of the CXL procedure for post-LASIK ectasia with the longest follow-up, it has limitations, such as its retrospective design and small cohort. With new techniques and advances in corneal imaging, LASIK candidates who have a risk factor for developing iatrogenic corneal ectasia can be easily identified and excluded from having LASIK. Thus, performing a prospective study with a large sample and long follow-up would be challenging. In summary, in this study corneal CXL appeared to stabilize the progression of post-LASIK ectasia without complications over a mean follow-up of 42 months. It also improved the UDVA, CDVA, maximum K value, and cylindrical refraction. WHAT WAS KNOWN  Corneal CXL has emerged as an effective technique to arrest progression of post-LASIK ectasia. WHAT THIS PAPER ADDS  Crosslinking in patients with post-LASIK keratectasia stabilized the progression of disease with a mean follow-up of 42 months, thereby avoiding or delaying keratoplasty.  Corneal CXL may improve the visual acuity, the maximum K value, and cylindrical refraction.

1595

REFERENCES 1. Randleman JB, Russell B, Ward MA, Thompson KP, Stulting RD. Risk factors and prognosis for corneal ectasia after LASIK. Ophthalmology 2003; 110:267–275 2. Comaish IF, Lawless MA. Progressive post-LASIK keratectasia; biomechanical instability or chronic disease process? J Cataract Refract Surg 2002; 28:2206–2213
JL, Salem TF, Artola A, Osman AA. Intracorneal rings to cor3. Alio rect corneal ectasia after laser in situ keratomileusis. J Cataract Refract Surg 2002; 28:1568–1574 4. Kymionis GD, Tsiklis NS, Pallikaris AI, Kounis G, Diakonis VF, Astyrakakis N, Siganos CS. Long-term follow-up of Intacs for post-LASIK corneal ectasia. Ophthalmology 2006; 113:1909–1917 5. Siganos CS, Kymionis GD, Astyrakakis N, Pallikaris IG. Management of corneal ectasia after laser in situ keratomileusis with INTACS. J Refract Surg 2002; 18:43–46 6. Kymionis GD, Diakonis VF, Kalyvianaki M, Portaliou D, Siganos C, Kozobolis VP, Pallikaris AI. One-year follow-up of corneal confocal microscopy after corneal cross-linking in patients with post laser in situ keratosmileusis ectasia and keratoconus. Am J Ophthalmol 2009; 147:774–778 7. Wollensak G, Spoerl E, Seiler T. Riboflavin/ultraviolet-A– induced collagen crosslinking for the treatment of keratoconus. Am J Ophthalmol 2003; 135:620–627. Available at: http:// grmc.ca/assets/files/collagen_crosslinking_2003_wollensak.pdf. Accessed June 5, 2014 8. Caporossi A, Baiocchi S, Mazzotta C, Traversi C, Caporossi T. Parasurgical therapy for keratoconus by riboflavin-ultraviolet type A rays induced cross-linking of corneal collagen; preliminary refractive results in an Italian study. J Cataract Refract Surg 2006; 32:837–845 9. Caporossi A, Mazzotta C, Baiocchi S, Caporossi T. Long-term results of riboflavin ultraviolet A corneal collagen cross-linking for keratoconus in Italy: the Siena Eye Cross Study. Am J Ophthalmol 2010; 149:585–593 10. Derakhshan A, Shandiz JH, Ahadi M, Daneshvar R, Esmaily H. Short-term outcomes of collagen crosslinking for early keratoconus. J Ophthalmic Vis Res 2011; 6:155–159. Available at: http:// www.ncbi.nlm.nih.gov/pmc/articles/PMC3306103/pdf/jovr-6-3155.pdf. Accessed June 5, 2014
P, Galiacy S, Arne
JL, Malecaze F. Cross-linking 11. Fournie ne corne
en induit par ultraviolet-A et riboflavine du collage
ratoco ^ne e
volutif [Corneal collagen dans le traitement du ke cross linking with ultraviolet-A light and riboflavin for the treatment of progressive keratoconus]. J Fr Ophtalmol 2009; 32:1–7 12. Grewal DS, Brar GS, Jain R, Sood V, Singla M, Grewal SPS. Corneal collagen crosslinking using riboflavin and ultraviolet-A light for keratoconus; one-year analysis using Scheimpflug imaging. J Cataract Refract Surg 2009; 35:425–432 13. Hafezi F, Mrochen M, Iseli HP, Seiler T. Collagen crosslinking with ultraviolet-A and hypoosmolar riboflavin solution in thin corneas. J Cataract Refract Surg 2009; 35:621–624 14. Raiskup-Wolf F, Hoyer A, Spoerl E, Pillunat LE. Collagen crosslinking with riboflavin and ultraviolet-A light in keratoconus: long-term results. J Cataract Refract Surg 2008; 34:796–801  E, Trazza S, Rosetta P, Vinciguerra R, 15. Vinciguerra P, Albe Seiler T, Epstein D. Refractive, topographic, tomographic, and aberrometric analysis of keratoconic eyes undergoing corneal cross-linking. Ophthalmology 2009; 116:369–378 16. Richoz O, Mavrakanas N, Pajic B, Hafezi F. Corneal collagen cross-linking for ectasia after LASIK and photorefractive keratectomy: long-term results. Ophthalmology 2013; 120: 1354–1359

J CATARACT REFRACT SURG - VOL 40, OCTOBER 2014

1596

CORNEAL CXL FOR POST-LASIK ECTASIA

17. Hersh PS, Greenstein SA, Fry KL. Corneal collagen crosslinking for keratoconus and corneal ectasia: one year results. J Cataract Refract Surg 2011; 37:149–160 18. Greenstein SA, Fry KL, Hersh PS. Corneal topography indices after corneal collagen crosslinking for keratoconus and corneal ectasia: one-year results. J Cataract Refract Surg 2011; 37:1282–1290 19. Greenstein SA, Fry KL, Hersh MJ, Hersh PS. Higher-order aberrations after corneal collagen crosslinking for keratoconus and corneal ectasia. J Cataract Refract Surg 2012; 38:292–302 20. Spoerl E, Huhle M, Seiler T. Induction of cross-links in corneal tissue. Exp Eye Res 1998; 66:97–103 21. Spoerl E, Seiler T. Techniques for stiffening the cornea. J Refract Surg 1999; 15:711–713 22. Wollensak G, Spoerl E, Seiler T. Stress-strain measurements of human and porcine corneas after riboflavin–ultraviolet-A-induced cross-linking. J Cataract Refract Surg 2003; 29:1780–1785 23. Spoerl E, Wollensak G, Seiler T. Increased resistance of crosslinked cornea against enzymatic digestion. Curr Eye Res 2004; 29:35–40 24. Labiris G, Giarmoukakis A, Sideroudi H, Gkika M, Fanariotis M, Kozobolis V. Impact of keratoconus, cross-linking and crosslinking combined with photorefractive keratectomy on selfreported quality of life. Cornea 2012; 31:734–739 25. Wittig-Silva G, Whiting M, Lamoureux E, Lindsay RG, Sullivan LG, Snibson GR. A randomized controlled trial of corneal collagen cross-linking in progressive keratoconus: preliminary results. J Refract Surg 2008; 24:S720–S725 26. Kohlhaas M, Spoerl E, Speck A, Schilde T, Sandner D, Pillunat LE. Eine neue Behandlung der Keratektasie nach LASIK durch Kollagenvernetzung mit Riboflavin/UVA-Licht [A new treatment of keratectasia after LASIK by using collagen with riboflavin/UVA light cross-linking]. Klin Monatsbl Augenheilkd 2005; 222:430–436  E, Trazza S. Corneal 27. Vinciguerra P, Camesasca FI, Albe collagen cross-linking for ectasia after excimer laser refractive surgery: 1-year results. J Refract Surg 2010; 26:486–497 28. Hafezi F, Kanellopoulos J, Wiltfang R, Seiler T. Corneal collagen crosslinking with ribofl avin and ultraviolet A to treat induced keratectasia after laser in situ keratomileusis. J Cataract Refract Surg 2007; 33:2035–2040 29. Salgado JP, Khoramnia R, Lohmann CP, Winkler von Mohrenfels C. Corneal collagen crosslinking in post-LASIK keratectasia. Br J Ophthalmol 2011; 95:493–497 30. Li G, Fan Z-J, Peng X-J. Corneal collagen crosslinking for corneal ectasia of post-LASIK: one-year results. Int

31.

32.

33.

34.

35.

36.

37.

38. 39.

40.

41.

42.

J Ophthalmol 2012; 5:190–195. Available at: http://www.ijo.cn/ gjyken/ch/reader/create_pdf.aspx?file_noZ201202015&year_ idZ2012&quarter_idZ2&falgZ1. Accessed June 5, 2014 Kymionis GD, Kounis GA, Portaliou DM, Grentzelos MA, Karavitaki AE, Coskunseven E, Jankov MR, Pallikaris IG. Intraoperative pachymetric measurements during corneal collagen cross-linking with riboflavin and ultraviolet A irradiation. Ophthalmology 2009; 116:2336–2339 Greenstein SA, Shah VP, Fry KL, Hersh PS. Corneal thickness changes after corneal collagen crosslinking for keratoconus and corneal ectasia: one-year results. J Cataract Refract Surg 2011; 37:691–700 Koller T, Iseli HP, Hafezi F, Vinciguerra P, Seiler T. Scheimpflug imaging of corneas after collagen cross-linking. Cornea 2009; 28:510–515 Koller T, Mrochen M, Seiler T. Complication and failure rates after corneal crosslinking. J Cataract Refract Surg 2009; 35:1358–1362 Kolli S, Aslanides IM. Safety and efficacy of collagen crosslinking for the treatment of keratoconus. Expert Opin Drug Saf 2010; 9:949–957 Sharma N, Maharana P, Singh G, Titiyal JS. Pseudomonas keratitis after collagen crosslinking for keratoconus: case report and review of the literature. J Cataract Refract Surg 2010; 36:517–520 Rama P, Di Matteo F, Matuska S, Paganoni G, Spinelli A. Acanthamoeba keratitis with perforation after corneal crosslinking and bandage contact lens use. J Cataract Refract Surg 2009; 35:788–791 Gokhale NS. Corneal endothelial damage after collagen crosslinking treatment. Cornea 2011; 30:1495–1498 Herrmann CIA, Hammer T, Duncker GIW. Haze-Bildung nach Vernetzungstherapie bei Keratokonus [Hazeformation (corneal scarring) after cross-linking therapy in keratoconus]. Ophthalmologe 2008; 105:485–487 Mazzotta C, Balestrazzi A, Baiocchi S, Traversi C, Caporossi A. Stromal haze after combined riboflavin-UVA corneal collagen cross-linking in keratoconus: in vivo confocal microscopic evaluation [letter]. Clin Exp Ophthalmol 2007; 35:580–582 Raiskup F, Hoyer A, Spoerl E. Permanent corneal haze after riboflavin-UVA-induced cross-linking in keratoconus. J Refract Surg 2009; 25:S824–S828 Greenstein SA, Fry KL, Bhatt J, Hersh PS. Natural history of corneal haze after collagen crosslinking for keratoconus and corneal ectasia: Scheimpflug and biomicroscopic analysis. J Cataract Refract Surg 2010; 36:2105–2114

J CATARACT REFRACT SURG - VOL 40, OCTOBER 2014