|Year : 2017 | Volume
| Issue : 2 | Page : 35-40
Evaluation of corneal collagen cross-linking with femtosecond laser-assisted intrastromal corneal ring segments in keratoconus
Mohamed Farouk Sayed Othman Abdelkader MD 1, Ezz El-Din Galal Mohamed1, Hesham Fathallah El-Sheikh2, Ahmed Maher Khalafallah1
1 Department of Ophthalmology, Faculty of Medicine, Minia University, Minia, Egypt
2 Department of Ophthalmology, Faculty of Medicine, Cairo University, Cairo, Egypt
|Date of Submission||05-Feb-2017|
|Date of Acceptance||21-Mar-2017|
|Date of Web Publication||20-Jul-2017|
Mohamed Farouk Sayed Othman Abdelkader
Department of Ophthalmology, Faculty of Medicine, Minia University, Minia, 61519
Source of Support: None, Conflict of Interest: None
Purpose The purpose of this article is to evaluate and compare the outcomes of simultaneous and successive femtosecond laser-assisted intrastromal corneal kera-ring segments insertion and corneal collagen cross-linking in the treatment of keratoconus.
Keywords: corneal cross-linking, femtosecond laser, kera-rings, keratoconus
|How to cite this article:|
Abdelkader MF, Mohamed EDG, El-Sheikh HF, Khalafallah AM. Evaluation of corneal collagen cross-linking with femtosecond laser-assisted intrastromal corneal ring segments in keratoconus. J Egypt Ophthalmol Soc 2017;110:35-40
|How to cite this URL:|
Abdelkader MF, Mohamed EDG, El-Sheikh HF, Khalafallah AM. Evaluation of corneal collagen cross-linking with femtosecond laser-assisted intrastromal corneal ring segments in keratoconus. J Egypt Ophthalmol Soc [serial online] 2017 [cited 2020 Dec 6];110:35-40. Available from: http://www.jeos.eg.net/text.asp?2017/110/2/35/211145
| Introduction|| |
Keratoconus is a noninflammatory progressive ectatic corneal disease with the onset at puberty in most cases . Corneal collagen cross-linking (CXL) is a recent treatment modality for kertaconus in which the stromal fibers are photoplymerized by the combined action of a photosenstizing substance (vitamin B2 or riboflavin) and ultraviolet rays A (UVA) . Photopolymerizatiom increases the rigidity of corneal collagen, slowing or arresting the progression of keratoconus to delay or avoid keratoplasty . Implantation of intrastromal corneal ring segments (ICRS) is a surgical procedure for keratoconus that can also delay or prevent keratoplasty ,,. ICRS implantation helps to regulate the front surface of the cornea while maintaining the existing biomechanical status of the underlying corneal stroma .
Femtosecond laser technology can be used to create intracorneal tunnels for ICRS implantation. The advantages of femtosecond laser over the mechanical method are that it is minimally invasive, provided more uniform dissection, and leads to more consistent results. Moreover, it causes less patient discomfort, provides faster visual recovery, and allows more accurate ICRS placement . The combination of CXL, ICRS, and femtosecond laser can yield good results because these procedures can complement each another. However, the ideal sequence of interventions is a subject of conterversy .
| Aim|| |
The aim of this work is to evaluate and compare the outcomes of simultaneous and successive femtosecond laser-assisted intrastromal corneal kera-ring segments insertion and CXL in the treatment of keratoconus.
| Patients and methods|| |
Twenty eyes of 14 patients with keratoconus were included in a prospective comparative interventional case-series study. This study was carried out in Minia University Hospital and Roaa Laser Vision Correction Center between June 2015 and May 2016. The study was approved by the Ethical Committee of the Faculty of Medicine, Minia University, and an informed written consent was obtained from all patients. Patients were classified into two groups:
Group A: 10 eyes were treated by femtosecond laser-assisted intrastromal corneal kera-ring segments insertion, followed by epithelium off corneal cross-linking 2 months later.
Group B: 10 eyes were treated by simultaneous femtosecond laser-assisted intrastromal corneal kera-ring segments insertion with epithelium off corneal cross-linking.
Patients included in this study were those with with keratoconus grades I–III according to the Amsler–Krumeich classification, age older than 16 years, corneal thickness of at least 400 μm at the thinnest corneal point, and at least 450 μm at the incision site with a clear corneal center. Exclusion criteria included patients with grade IV keratoconus, acute hydrops, keratometric readings greater than 65 D, history of herpetic keratitis, corneal dystrophies, opacities or scarring, autoimmune or systemic connective tissue disease, any other ocular diseases (cataract, glucoma, retinopathies, and others), and patients with previous corneal or intraocular surgeries.
All patients were subjected to the following:
Full assessment of history, slit-lamp examination, refraction (manifest and cycloplegic), uncorrected visual acuity, and best-corrected visual acuity (BCVA) using Snellen’s decimal values, fundus examination by indirect ophthalmoscopy, intraocular pressure by tonopen (Reichart Inc., NY, USA), and preoperative and postoperative Pentacam examination (Oculus, Optikgerate GmbH, Munich, Germany).
Instillation of topical anesthesia (benoxinate hydrochloride 0.4%) was performed and the eyelids and the surrounding skin were prepared using povidone iodine 10%, followed by surgical drape and lid speculum application. The creation of the intrastromal tunnel for kera ring was performed by 150 kHz femtosecond technology (IntraLase; Abbott; Abbott Laboratories, 100 Abbott Park Road Abbott Park, Illinois, USA). An inner diameter of 5.0 mm, an outer diameter of 5.9 mm, an entry cut length of 1.40 mm, an entry cut thickness of 1 μm, and an entry cut power of 1.9 mJ were programmed with the laser soft ware. The vacuum was created manually using a sterile, spring-loaded syringe attached to the vacuum ring. Then, the sterile, disposable docking cone was mounted on the head of the laser and brought down onto the eye. An intrastromal tunnel of 80% of the thickness of the thinnest location in depth was created. A corneal incision of arc length was determined according to the size of the ring and then kera ring was inserted into the tunnel by the corneal incision. The nomogram of the manufacturer, Mediphacos (Av. Deputado Cristovam Chiaradia, 777 - Buritis, Belo Horizonte - MG, 30575-815, Brazil), was used to select the proper ring segment needed for implantation. The kera-ring segments were inserted into the corneal tunnels by the corneal incision using a special forceps with a groove to accommodate the ring (modified Macpherson forceps). The corneal incision was self-sealing and no suturing was required. Topical moxifloxacin was instilled. Then, a soft contact lens was applied.
Corneal collagen cross-linking technique
After application of diluted alcohol 20% for 30 s, mechanical debridement of corneal epithelium over the central 9–10 mm was performed using a blunt instrument. 0.1% Riboflavin in a 20% hydroxymethyl propyl cellulose solution (vibex rapid; Avedro Inc., Waltham, Massachusetts, USA) was instilled topically every 2 min for 10 min. The cornea was then exposed to UVA light of 366–374 nm at an irradiance of 30 mW/cm2 for 8 min (Avedro Inc.). Riboflavin instillation was continued every 2 min during exposure to UVA light. At the end of the procedure, topical moxifloxacin and a soft contact lens were applied. Antibiotic drops and artificial tears were continued till complete corneal re-epithelialization occurred. After epithelial healing, the contact lens was removed and corticosteroid drops were used and gradually tapered over 3–4 weeks, and stopped at the postoperative first-month follow-up visit. Artificial tears were continued for 2 months.
In the simultaneous technique, femtosecond-assisted ICRS implantation was performed first, followed by removal of the epithelium and CXL.
At the postoperative visits at 3 and 6 months, the patients were examined for BCVA, manifest refraction, K-readings, and pachymetry using pentacam.
Data were entered and analyzed using SPSS, version 19. Graphics were obtained by excel. Quantitative data were presented as mean and SD, whereas qualitative data were presented as frequency distribution. The McNemar test was used to test the significant differences between preoperative values and 3-month postoperative values, preoperative values and 6-month postoperative values, and between 3-month postoperative values and 6-month postoperative values in each group. Comparison between groups was carried out using the Mann–Whitney test. Spearman’s correlation was used. A probability of less than 0.05 was used as the cut-off for significance.
| Results|| |
Group A included 10 eyes of six patients (four bilateral and two unilateral), three (50%) men and three (50%) women, mean age 26.2±6.2 years (range: 17–35 years). Group B included 10 eyes of eight patients (two bilateral and six unilateral), five (62.5%) men and three (37.5%) women, mean age 27.3±5.8 years (range: 20–36 years).
In group A, the mean preoperative BCVA was 0.34±0.1 (range: 0.2–0.6) whereas the mean postoperative BCVA at three months was 0.54±0.1 (range: 0.3–0.7), increasing by a mean of 0.2±0.09, with a P value of 0.001. At 6 months, the mean BSCVA was 0.50±0.1 (range: 0.2–0.7) and decreased by a mean of 0.04±0.5 compared with BCVA at 3 months, with a P value of 0.03.
However, in group B, the mean preoperative BCVA was 0.25±0.1 (range: 0.1–0.6), whereas the mean postoperative BSCVA at 3 months was 0.41±0.1, ranging from 0.1 to 0.7, increasing significantly by a mean of 0.16±0.08 with a P value of 0.001. At 6 months, the mean BSCVA was 0.40±0.1 (range: 0.1–0.7) and decreased insignificantly by a mean of 0.01±0.05 compared with BCVA at 3 months, with a P value of 0.5. [Figure 1] presents a comparison of the changes in BCVA preoperatively and after 3 and 6 months between the two groups. No statistically significant difference was present between the two groups.
|Figure 1 Graph showing BCVA changes in both groups, preoperative and postoperative at 3 and 6 months|
Click here to view
In group A, the mean preoperative mean K was 48.9±3.3 D (45.1–58.1 D). The mean postoperative mean K was 45.3±2.3 D (41.7–48.7 D) at 3 months and was 45.6±2.3 D (42–48.9 D) at 6 months. Compared with the preoperative mean K-readings, there was a statistically significant decrease in the mean K at 3 months by 3.5±2.1 D (P=0.001). There was a statistically insignificant increase in the mean K-reading at 6 months compared with that at 3 months by a mean increase of 0.2±0.4 D (P=0.1).
In group B, the mean preoperative mean K was 50.9±3.8 D (45.1–54.2 D). The mean postoperative mean K at 3 months was 48.6±3.1 D (range: 46–54.2 D) and that at 6 months was 48.5±3.2 D (45.8–54 D). Compared with the preoperative mean K-readings, there was a statistically significant decrease in the mean K at 3 months by 3.8±1.5 D (P=0.001). There was a statistically insignificant increase in the mean K-reading at 6 months compared with that at 3 months, by a mean increase of 0.02±0.6 D (P=0.9). No statistically significant difference was present in K-readings changes preoperatively, and after 3 and 6 months among the two groups ([Table 1])
[Table 2] presents the changes in the pachymetery at the thinnest location and at the corneal apex in the two groups.
|Table 2 Changes in the pachymetery at the thinnest location and corneal apex throughout this study group and its significance using the paired t-test in both groups|
Click here to view
Comparing the corneal thickness changes after 6 months among the two groups, it was found that there was a greater decrease in corneal thickness at the thinnest location and at the apex in group B postoperatively, which is still statistically insignificant ([Table 3]).
In terms of the changes in refraction, in the groups, all changes in spherical and cylindrical refractions were statistically significant, except for spherical and cylindrical refractions between 3 and 6 months, which showed a statistically insignificant increase in the P value of 0.3 for sphere and P value of 0.2 for the cylinder. Also, in group B, all changes in spherical and cylindrical refractions were statistically significant, except for spherical and cylindrical refractions between 3 and 6 months, which showed a statistically insignificant increase in the P value of 0.4 for the sphere and 0.6 for the cylinder ([Table 4]).
In terms of postoperative complications, both groups developed a temporary corneal haze in all eyes after CXL with different degrees detected by slit-lamp and gradually disappeared within one month with steroid treatment. Night glare and haloes occurred in 80% of patients (eight out of 10 patients) in group A and 90% of patients (nine out of 10 patients) in group B and disappeared after 3 months. No delayed re-epithelialization occurred in any of the patients in both groups. [Figure 2] shows the postoperative appearance of the cornea in both groups after 6 months and [Figure 3] represents the preoperative and 6-month postoperative Pentacam 4 Maps scan in both groups.
|Figure 2 Postoperative appearance of the cornea in both groups after 6 months|
Click here to view
|Figure 3 Preoperative and 6 months post-operative Pentacam 4 Maps scan in both groups|
Click here to view
| Discussion|| |
Both CXL and femtolaser-assisted ICRS are reliable modalities for the treatment of keratoconus. The combination of CXL and ICRS should yield better results because these procedures complement one another to stop the progression of the disease.
The study was a prospective comparative interventional case series that was carried out on 14 patients (20 eyes) comparing sequential (group A) versus simultaneous (group B) femtosecond laser-assisted intrastromal kera-ring segments insertion and CXL. The diagnosis was made on the basis of slit-lamp and pentacam examinations. Keratoconus cases were classified according to the Amsler–Krumeich grading system. The criteria for eligibility were keratoconus grades I–III for suitability for these surgical procedures.
Patients younger than 16 years old were excluded from the study because the size and the shape of the pediatric corneas change throughout infancy and childhood until they stabilize on reaching adulthood. In terms of corneal thickness, it was at least 400 μm at the thinnest corneal point and at least 450 μm at the incision site to avoid corneal perforation during keraring implantation and CXL cytotoxic effects on the corneal endothelium and other intraocular tissues.
There was a significant improvement in BCVA after 6 months (P=0.002 in group A and 0.002 in group B). This is in agreement with Coskunseven et al. , who carried out a study on 23 eyes with keratoconus treated with ICRS, followed by CXL after 7 months. They showed a statistically significant improvement in BCVA after 6 months by a mean of 0.33±0.09 Snellen’s lines with a P value 0.001.
El-Raggal  reported similar results. He carried out a study on two groups: one was treated with ICRS, followed by CXL after 6 months (nine eyes) and the other was treated simultaneously during the same session (seven eyes). There was a statistically significant improvement in BCVA in both groups, with no statistically different results between both groups. The mean preoperative BCVA in the first group was 0.36±0.12, and after 6 months the mean BCVA was 0.72±0.15, with a significant increase by a mean of 0.36±0.09 Snellen’s lines with a P value 0.001, whereas in the second group, the mean preoperative BCVA was 0.33±0.11, and after 6 months, the mean BCVA was 0.69±0.11, increasing significantly by a mean of 0.36±0.11 Snellen’s lines with a P value 0.001. The P value between the groups was 0.59.
In the current study, there was a statistically significant flattening (improvement) of the mean K after 6 months in group A by a mean of 3.3±0.89 D compared with the preoperative mean K, with a P value of 0.001. In group B, there was a statistically significant flattening of the mean K after 6 months by a mean of 3.7± 0.11 D compared with the preoperative mean K, with a P value of 0.001. There was no statistically difference between both groups, with a P value of 0.1.
This is mostly in agreement with El-Raggal , who reported a statistically significant flattening of the mean K after 6 months in the first group by a mean of 3.1±0.82 D compared with the preoperative mean K, with a P value of 0.001, and in the second group by a mean of 5.1±0.92 D compared with the preoperative mean K, with a P value of 0.001. However, they found a statistically significant difference between both groups (P=0.046), with more reduction in keratometric readings in the second group, which was treated by simultaneous ICRS and CXL during the same session. The difference in the results may be related to the difference in the period between the two procedures in the first group (6 months in El-Raggal’s  study vs. 2 months in the current study). Also, the smaller number of eyes in the second group in El-Raggal’s  study (seven eyes) may be another reason for the difference.
The improvement in keratometric readings is also in agreement with Coskunseven et al.  and Ertan et al. .
In terms of corneal pachymetry, the mean preoperative thinnest location thickness in group A was 452.7±26.1 μm, whereas after 6 months, it was 449.9±23.1 μm, with a statistically insignificant decrease, with a P value of 0.4, whereas in group B, the mean preoperative thinnest location thickness in group A was 461±44.9 μm, whereas after 6 months, it was 438.2±38.5 μm, with a statistically significant decrease, with a P value of 0.04, but on comparing the changes in both groups, there were no statistically significant differences among both groups (P=0.4 at 6 months). This is in agreement with the study carried out by Coskunseven et al. , where there was no significant reduction in the pachymetric values as the preoperative thickness was 424±37 μm and at 6 months postoperatively, it was 423±29 μm (P=0.88).
In terms of the spherical and cylindrical refractive errors in both groups, all changes in spherical and cylindrical refractions were statistically significant, except for spherical and cylindrical refractions between 3 and 6 months. Comparing the results among the two groups, there were statistically insignificant differences in spherical and cylindrical refractions. This is in agreement with El-Raggal , who reported statistically significant changes in spherical refractions in both groups with a P value of 0.001 and in cylindrical refractions with P values of 0.018 and 0.045 in groups A and B, respectively, with no significant differences between both groups.
Apart from temporary corneal edema and haze, which resolved gradually after 1 month with topical steroid treatment, no adverse effects were detected throughout study. This is in agreement with the results of Caporossi et al.  and De Bernardo et al. .
| Conclusion|| |
Both techniques of simultaneous and successive femtosecond laser-assisted intrastromal corneal kera-ring segments and CXL are effective and safe for the management of kertoconus.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Rabinowitz YS. Keratoconus. Surv Ophthalmol 1998; 42:297–319.
Wollensak G, Spoerl E, Seiler T. Riboflavin/ultraviolet A-induced collagen crosslinking for the treatment of keratoconus. Am J Ophthalmol 2003; 135:620–627.
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.
Colin J, Cochener B, Savary G, Malet F. Correcting keratoconus with intracorneal rings. J Cataract Refract Surg 2000; 26:1117–1122.
Alio JL, Shabayek MH, Artola A. Intracorneal ring segments for keratoconus correction: long-term follow-up. J Cataract Refract Surg 2006; 32:978–985.
Burris TE, Ayer CT, Evensen DA, Davenport JM. Effects of intrastromal corneal ring size and thickness on corneal flattening in human eyes. Refract Corneal Surg 1991; 7:46–50.
Coskunseven E, Jankov MR II, Hafezi F, Atun S, Arslan E, Kymionis GD. Effect of treatment sequence in combined intrastromal corneal rings and corneal collagen crosslinking for keratoconus. J Cataract Refract Surg 2009; 35:2084–2091.
Ratkay-Traub I, Ferincz IE, Juhasz T, Kurtz RM, Krueger RR. First clinical results with the femtosecond neodynium-glass laser in refractive surgery. J Refract Surg 2003; 19:94–103.
El-Raggal TM. Effect of corneal collagen crosslinking on femtosecond laser channel creation for intrastromal corneal ring segment implantation in keratoconus. J Cataract Refract Surg 2011; 37:701–705.
El-Raggal TM. Sequential versus concurrent kera-rings insertion and corneal collagen cross-linking for keratoconus. Br J Ophthalmol 2010; 95:37–41.
Ertan A, Kamburoğlu G, Bahadir M Intacs insertion with the femtosecond laser for the management of keratoconus: one-year results. J Cataract Refract Surg 2006; 32:2039–2042.
Caporossi A, Mazzotta C, Paradiso AL, Baiocchi S, Marigliani D, Caporossi T. Transepithelial. Corneal collagen crosslinking for progressive keratoconus: 24-month clinical results. J Cataract Refract Surg 2013; 39:1157–1163.
De Bernardo M, Capasso L, Tortori A. Trans epithelial corneal collagen crosslinking for progressive keratoconus: 6 months follow up. Cont Lens Anterior Eye 2014; 37:438–441.
[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2], [Table 3], [Table 4]