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 Table of Contents  
Year : 2016  |  Volume : 17  |  Issue : 3  |  Page : 123-127

Simultaneous versus sequential photorefractive keratectomy and cross-linking for the management of early keratoconus

Department of Ophthalmology, Faculty of Medicine, Zagazig University, Zagazig, Egypt

Date of Submission25-May-2016
Date of Acceptance31-Aug-2016
Date of Web Publication6-Dec-2016

Correspondence Address:
Ashraf Bor'i
Department of Ophthalmology, Faculty of Medicine, Zagazig University, Zagazig 22486
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/1110-9173.195268

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The aim of this study was to compare the safety and efficacy of simultaneous topography-guided photorefractive keratectomy (PRK) and corneal collagen cross-linking (CXL) with consecutive topography-guided PRK and CXL.
Patients and methods
A total of 34 eyes with early keratoconus were enrolled in this clinical study and assigned into two groups. Group A (n=17 eyes) underwent topography-guided PRK with CXL on the same day (the simultaneous group), and group B (n=17 eyes) underwent topography-guided PRK followed by CXL after 6 months (the sequential group). Changes in uncorrected and best-corrected visual acuity, spherical equivalent, keratometry (K), topography, and central corneal thickness were recorded. Follow-up was 12 months.
The mean uncorrected visual acuity improved from 0.2±0.02 to 0.5±0.06 postoperatively in the simultaneous group at 12 months, whereas in the sequential group it improved from 0.25±0.03 to 0.5±0.08 (P=0.3). Best-corrected visual acuity improved from 0.4±0.25 to 0.8±0.3 postoperatively in the simultaneous group, whereas it improved from 0.5±0.12 to 0.7±0.2 in the sequential group (P=0.25). The mean spherical equivalent in the simultaneous group improved from –3.25±0.25 to –1.25±0.35 D with a mean reduction by 2.12±0.15 D, whereas in the sequential group it improved from –3.75±0.28 to –1.5±0.21 D with a reduction of 2.25±0.27 D (P=0.24). The mean reduction in K reading was 3.18±0.99 D in group A and 3.25±1.2 D in group B.
The same results have been obtained in both groups as regards the visual outcome in early cases with keratoconus.

Keywords: collagen cross-linking, keratoconus, photorefractive keratectomy

How to cite this article:
Bor'i A. Simultaneous versus sequential photorefractive keratectomy and cross-linking for the management of early keratoconus. Delta J Ophthalmol 2016;17:123-7

How to cite this URL:
Bor'i A. Simultaneous versus sequential photorefractive keratectomy and cross-linking for the management of early keratoconus. Delta J Ophthalmol [serial online] 2016 [cited 2022 Jan 26];17:123-7. Available from: http://www.djo.eg.net/text.asp?2016/17/3/123/195268

  Introduction Top

Keratoconus, which is a bilateral, nonsymmetrical, and progressive protrusion and thinning of the cornea, may lead to severe visual impairment due to irregular astigmatism and corneal opacities [1].

Spectacle prescription, contact lens use, and corneal ring segments have been used to improve the visual acuity in eyes with early or mild keratoconus [2].

The use of topography-guided excimer laser to improve the corneal surface irregularities seems to be very helpful. Customized photorefractive keratectomy (PRK) has been used to treat corneal disorders associated with irregular cornea, such as keratoconus and postkeratoplasty astigmatism [3].

It has been used in eyes with stable or early keratoconus, resulting in improved visual acuity. However, reduction in the corneal strength due to the removal of corneal lamellae during ablation may lead to more protrusion of the cone [4],[5].

Corneal cross-linking (CXL) has been used to strengthen the cornea and hence prevent further progression, but the visual outcome of the treated patients is still unsatisfactory [6].

The use of CXL with PRK has been described as a procedure to treat early and stable keratoconus. It offers improvements in both visual acuity and topographic irregularity [7],[8].

A nonrandomized prospective study was conducted to compare the outcome of simultaneous topography-guided PRK and CXL with that of PRK followed by CXL after 6 months in patients with early keratoconus.

  Patients and methods Top

Thirty-four eyes of 29 patients with early keratoconus were included in this study. Informed written consent was obtained from all patients after explanation of the techniques and the possible risks they may encounter. Patients were divided randomly into two groups, group A and group B. Patients in group A (17 eyes) were treated with PRK followed by CXL at the same sitting, whereas patients in group B (17 eyes) were treated with PRK and after 6 months CXL was performed. All the procedures performed were in accordance with the ethical standards of the institutional and /or national research committee and adhered to the tenets of Helsinki declaration.

A complete eye examination was carried out, including uncorrected (UCVA) and best-corrected visual acuity (BCVA), manifest refraction with spherical equivalent (SE), and slit-lamp biomicroscopy. Preoperative Scheimpflug-based corneal tomography (Pentacam; Oculus, Lynnwood, Washington, USA) was performed.

All patients had grade I or II keratoconus according to the Krumeich classification of keratoconus [7]. SE was less than –6.5 D, Kmin value less than 50 D, and corneal thickness more than 400 μm.

Patients in group A (17 eyes) underwent correction with both PRK followed by CXL in the same sitting. After instillation of topical anesthetic agent, 8-mm diameter zone was de-epithelialized from the center of the cornea with 20% alcohol for 30 s in all eyes.

The ablation was performed using the Alcon EX-500 (Wave-Light GmbH, Erlangen, Germany). After PRK, CXL procedure was performed.

Riboflavin 0.1% solution (10 mg riboflavin in 20% dextran solution; Ricrolin; SOOFT Italia S.p.A., Montegiorgio, Italy) was instilled on the cornea for a duration of 20 min. Ultraviolet A emitter Vega CBM X-linker (SOOFT Italia S.p.A.) was then used for 30 min.

Patients in group B (17 eyes) underwent PRK correction with the same previous parameters and after 6 months they were treated with CXL.

Finally, a bandage contact lens was applied. The same treatment was used in both groups with 0.3% gatifloxacin eye drops five times per day with 1% prednisolone phosphate eye drops three times per day until the removal of contact lens when corneal re-epithelialization occurred, and then the frequency of the steroid eye drops was increased to five times per day.

All patients were followed up daily until epithelialization of the cornea, and then after 1, 3, 6, and 12 months.

Unaided and aided visual acuity, manifest refraction, slit-lamp examination, and pentacam were recorded at each postoperative visit.

  Results Top

The mean patient’s age in group A (the simultaneous group) was 23.7 years (range=19–31 years) and comprised eight male and seven female patients. The follow-up period was 12 months. The mean patient’s age in group B (the sequential group) was 22.8 years (range=20–32 years) and comprised seven male and seven female patients. The follow-up period was 12 months from the time of the last procedure (CXL) ([Table 1]).
Table 1 Preoperative demographic data

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The mean corneal thickness in group A was 453±25 μm (range=412–500 μm). However, it was 441±29 μm (range=409–498 μm) in group B. The ablation depth was not more than 50 μm in all cases.

The mean UCVA in group A was 0.2±0.02 preoperatively (range=0.16–0.5) and improved postoperatively to 0.5±0.06 (range=0.3–0.7). However, the mean UCVA improved from 0.25±0.03 (range=0.16–0.4) to 0.5±0.08 (range=0.2–0.7) in group B (P=0.3) ([Table 2]).
Table 2 Visual acuity and spherical equivalent in both groups

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The mean BCVA improved from 0.4±0.25 (range=0.25–0.8) to 0.8±0.3 (range=0.5–1.0) postoperatively in group A, whereas it improved from 0.5±0.12 (range=0.3–0.7) preoperatively to 0.7±0.2 (range=0.6–1.0) postoperatively in group B (P=0.25) ([Table 2]).

The mean SE in group A improved from –3.25±0.25 D (range=–1.75 to –6.5 D) to –1.25±0.35 D (range=–0.75 to –3.25 D) with a mean reduction of 2.12±0.15 D (range=1.75–2.25 D). However, in group B it improved from –3.75±0.28 D (range=–1.5 to –6.25 D) to –1.5±0.21 D (range=–0.75 to –3.00 D) with a mean reduction of 2.25±0.27 D (range=1.75–2.50 D) (P=0.24, not significant) ([Table 2] and [Figure 1]).
Figure 1 Spherical Equivalent (SE).

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In group A, the mean average K reading was 45.21±15.4 D preoperatively and changed to 43.65±5.18 D postoperatively. In group B, the mean K reading was 46.01±9.02 D and changed to 43.92±6.32 D postoperatively (P=0.035) ([Table 3]).
Table 3 Topographic findings in both groups

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  Discussion Top

Treatment of keratoconus with both PRK and CXL seems to be a good option for stabilizing the corneal biomechanical properties and achieving a more regular cornea with a better visual acuity [9].

Topography-guided PRK flattens the cone peak and aids in normalization of the corneal surface [10].

CXL can help in improving the biomechanics of the cornea. This depends on the absorption of UVA spectrum by the cornea after the riboflavin is instilled on the corneal tissue [11].

This prospective study compared simultaneous PRK and CXL with sequential PRK followed by CXL as regards the corrected and UCVA, manifest refraction, and topographic findings.

UCVA improved from 0.2±0.02 to 0.5±0.06 postoperatively, with no significant difference in group A, whereas it improved from 0.25±0.03 to 0.5±0.08 in group B. BCVA improved from 0.4±0.25 to 0.8±0.3 postoperatively in group A, whereas it improved from 0.5±0.12 to 0.7±0.2 in group B, which is also nonsignificant.

The mean SE in group A improved from –3.25±0.25 to −1.25±0.35 D with a mean reduction by 2.12±0.15 D. In group B it improved from −3.75±0.28 to –1.5±0.21 D with a mean reduction of 2.25±0.27 D.

Anastasios [12] in his research on 325 eyes with keratoconus assigned the included eyes into two groups. The first group underwent CXL followed by PRK performed 6 months later (the sequential group) and the second group underwent CXL together with PRK (the simultaneous group). He found improvement in the unaided and aided visual acuity and the SE. He concluded that the simultaneous group was superior as regards the improvement when compared with the sequential group. He attributed the difference between the two groups to the enhanced CXL in the simultaneous group either due to better diffusion of riboflavin through the treated stromal collagen or to the disappearance of the Bowman’s membrane by the ablation.

Kanellopoulos and Binder [13] proposed a two-step procedure with corneal CXL and PRK after a 1-year interval. They found that there were three limitations with this approach. First, the stiffened cross-linked corneal tissue is removed during the PRK (potentially decreasing the possible benefits of CXL). Second, the efficacy of this approach is limited because the corneal ablation rate could be different in cross-linked corneas than in the virgin cornea (this could lead to unpredictable refractive results). Third, there is an increased possibility of postoperative PRK haze formation (following CXL, the anterior stroma is repopulated by new keratocytes after 6 months). Thus, in the present study topography-guided PRK was performed followed by CXL. Therefore, there is no ablation of the previously cross-linked corneal lamellae.

George et al. [14], in their study on 14 eyes with keratoconus treated with surface ablation followed by CXL, concluded that the simultaneous PRK followed by CXL offers a good solution for eyes with keratoconus. They found that the mean preoperative SE was −3.03±3.23 D, which was statistically significantly reduced to −1.29±2.05 D (P=0.01). Preoperative mean UCVA was 0.99±0.81 and BCVA was 0.21±0.19, which improved postoperatively to 0.16±0.15 and 0.11±0.15, respectively.

Spadea and Paroli [15] studied the effect of simultaneous topography-guided PRK followed by CXL after lamellar keratoplasty for keratoconus. They found that the mean SE was markedly reduced, with an improvement in UCVA in all patients. Only two myopic patients had a mild overcorrection of 1.0 D. The manifest SE was reduced in all patients to a statistically significant extent, with no regression 12 months postoperatively.

Alessio et al. [16]compared PRK followed by CXL with only CXL for the treatment of keratoconus. They treated 34 eyes with progressive keratoconus. The eyes were assigned into two groups: the eyes with more advanced keratoconus (17 eyes) were assigned to the PRK plus CXL group and those with less advanced degree of disease (17 fellow eyes) were assigned to the CXL group. They found that, in the first group, the UCVA improved significantly from 0.63±0.36 to 0.19±0.17 (P<0.05) and BCVA from 0.06±0.08 to 0.03±0.06 (P<0.05). Manifest SE improved significantly (P<0.05). In the second group, UCVA improved, but not significantly, from 0.59±0.29 to 0.52±0.29, and BCVA improved from 0.06±0.11 to 0.04±0.07 (P>0.05). Manifest SE improvement was not significant (P>0.05). They concluded that the combined use of topography-guided PRK and CXL offers good results to ameliorate aberrations and strengthen keratoconic corneas.

From the present study, it can be concluded that the topography-guided PRK with CXL has the same results and is as effective as treatment with topography-guided PRK followed by CXL after 6 months for the treatment of early keratoconus.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

  References Top

Alpins N, Stamatelatos G. Customized photo-astigmatic refractive keratectomy using combined topographic and refractive data for myopia and astigmatism in eyes with forme fruste and mild keratoconus. J Cataract Refract Surg 2007; 33:591–602.  Back to cited text no. 1
Kanellopoulos AJ, Pe LH, Perry HD, Donnenfeld ED. Modified intracorneal ring segment implantations (INTACS) for the management of moderate to advanced keratoconus: efficacy and complications. Cornea 2006; 25:29–33.  Back to cited text no. 2
La Tegola MG, Alessio G, Sborgia C. Topographic customized photorefractive keratectomy for regular and irregular astigmatism after penetrating keratoplasty using the LIGI CIPTA/Laser-Sight platform. J Refract Surg 2007; 23:681–693.  Back to cited text no. 3
Cennamo G, Intravaja A, Boccuzzi D, Marotta G, Cennamo G. Treatment of keratoconus by topography-guided customized photorefractive keratectomy: two-year follow-up study. J Refract Surg 2008; 24:145–149.  Back to cited text no. 4
Spadea L. Collagen cross-linking for ectasia following PRK performed in excimer laser-assisted keratoplasty for keratoconus. Eur J Ophthalmol 2012; 22:274–277.  Back to cited text no. 5
Vinciguerra P, Camesasca FI, Albe‘ E, Trazza S. Corneal collagen cross-linking for ectasia after excimer laser refractive surgery: 1-year results. J Refract Surg 2010; 26:486–497.  Back to cited text no. 6
Ewald M, Kanellopoulos J. Limited topography-guided surface ablation (TGSA) followed by stabilization with collagen cross-linking with UV irradiation and riboflavin (UVACXL) for keratoconus (KC). Invest Ophthalmol Vis Sci 2008; 49:38–43.  Back to cited text no. 7
Labiris G, Giarmoukakis A, Sideroudi H, Gkika M, Fanariotis M, Kozobolis V. Impact of keratoconus, cross-linking and cross-linking combined with photorefractive keratectomy on self-reported quality of life. Cornea 2012; 31:734–739.  Back to cited text no. 8
Kanellopoulos AJ. Long-term safety and efficacy follow-up of prophylactic higher fluence collagen cross-linking in high myopic laser-assisted in situ keratomileusis. Clin Ophthalmol 2012; 6:1125–1130.  Back to cited text no. 9
Kanellopoulos AJ. Managing highly distorted corneas with topography-guided treatment. In: Eurotimes ISRS/AAO 2007 Subspecialty Day/Refractive Surgery Syllabus. Section II: ablation strategies San Francisco, California: American Academy of Ophthalmology; 2007. 13–15.  Back to cited text no. 10
Mazzotta C, Balestrazzi A, Traversi C, Baiocchi S, Caporossi T, Tommasi C, Caporossi A. Treatment of progressive keratoconus by riboflavin-UVA-induced cross-linking of corneal collagen: ultrastructural analysis by Heidelberg Retinal Tomograph II in vivo confocal microscopy in humans. Cornea 2007; 26:390–397.  Back to cited text no. 11
Anastasios JK. Comparison of sequential vs same-day simultaneous collagen cross-linking and topography-guided PRK for treatment of keratoconus. J Refract Surg 2009; 25:812–818.  Back to cited text no. 12
Kanellopoulos AJ, Binder PS. Collagen cross-linking (CCL) with sequential topography-guided PRK: a temporizing alternative for keratoconus to penetrating keratoplasty. Cornea 2007; 26:891–895.  Back to cited text no. 13
George DK, Georgios AK, George AK, Dimitra MP, Alexandra EK, Michael M et al. Simultaneous topography-guided PRK followed by corneal collagen cross-linking for keratoconus followed by corneal collagen cross-linking for keratoconus. J Refract Surg 2009; 25:807–811.  Back to cited text no. 14
Spadea L, Paroli M. Simultaneous topography-guided PRK followed by corneal collagen cross-linking after lamellar keratoplasty for keratoconus. Clin Ophthalmol 2012; 6:1793–1800.  Back to cited text no. 15
Alessio G, L’abbate M, Sborgia C, Gabriella M. Photorefractive keratectomy followed by cross-linking versus cross-linking alone for management of progressive keratoconus: two-year follow-up. Am J Ophthalmol 2013; 155:54–65.  Back to cited text no. 16


  [Figure 1]

  [Table 1], [Table 2], [Table 3]

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