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ORIGINAL ARTICLE
Year : 2015  |  Volume : 28  |  Issue : 1  |  Page : 168-173

Scheimpflug camera changes after cross-linking for keratoconus


1 Department of Ophthalmology, Faculty of Medicine, Menoufia University, Shebin El-kom, Egypt
2 Department of Ophthalmology, Research Institute of Ophthalmology, Giza, Egypt

Date of Submission22-May-2014
Date of Acceptance12-Jul-2014
Date of Web Publication29-Apr-2015

Correspondence Address:
Mark Frederic Berge Ananian
14 Alfy Street, Cairo 11111
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/1110-2098.155981

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  Abstract 

Objectives
The aim of our study was to evaluate corneal changes after corneal collagen cross-linking (CXL) in progressive keratoconus with Pentacam Scheimpflug imaging.
Background
Corneal collagen CXL using ultraviolet A light and riboflavin was introduced as a method to halt the progression of keratoconus. Scheimpflug imaging is considered among the most prevalent modalities in the diagnosis, staging, and follow-up of keratoconus patients.
Materials and methods
This study was a prospective interventional study that included 23 eyes of 18 patients with a mean age 23.39 ± 5.83 years with keratoconus. All underwent corneal collagen CXL using riboflavin and ultraviolet A light. Uncorrected visual acuity and best-corrected visual acuity were assessed. Pentacam's K1 , K2 , thickness at thinnest corneal point, anterior corneal elevation, posterior corneal elevation, cylindrical power and axis, and aberration coefficient were all determined before CXL, 3, and 6 months after CXL.
Results
There was improvement of uncorrected visual acuity from 0.16 ± 0.2 to 0.24 ± 0.21 (P = 0.001) and best-corrected visual acuity from 0.46±0.19 to 0.63 ± 0.24 after 6 months (P < 0.001). Significant decreases after 6 months were found in keratometry values: K1 from 47.69 ± 4.02 to 47.04 ± 4.43 D (P = 0.004) and K2 from 51.74 ± 4.76 to 51.03 ± 4.92 D (P < 0.001). In addition, there was decrease in thickness at thinnest corneal point from 448.04 ± 32.3 to 438.35 ± 35.42 mm (P = 0.025), anterior elevation from +34.17 ± 13.6 to +30.65 ± 11.11 mm (P = 0.06), and posterior elevation from +74.04±25.71 to +67.39 ± 23.09 mm (P = 0.03). Corneal cylinder and aberration coefficient showed stability with no significant change.
Conclusion
There is increasing evidence that CXL does not only halt the progression in the keratoconic eye by corneal tissue strengthening, but also improves visual outcomes and corneal shape, which are against the natural course of the disease.

Keywords: Corneal topography, cross-linking reagents, keratoconus


How to cite this article:
El Saadany AK, Al-Balkini MS, El Sawy MF, Ananian MF. Scheimpflug camera changes after cross-linking for keratoconus. Menoufia Med J 2015;28:168-73

How to cite this URL:
El Saadany AK, Al-Balkini MS, El Sawy MF, Ananian MF. Scheimpflug camera changes after cross-linking for keratoconus. Menoufia Med J [serial online] 2015 [cited 2019 Jun 26];28:168-73. Available from: http://www.mmj.eg.net/text.asp?2015/28/1/168/155981


  Introduction Top


Keratoconus is a condition of cornea characterized by asymmetric, bilateral, progressive, and noninflammatory ectasia due to the instability of cornea. The prevalence in general population is 50-200/100 000 [1]. It seems to occur in all populations throughout the world, although it may occur more frequently in certain ethnic groups. The exact cause of keratoconus is uncertain, but it has been associated with detrimental enzyme activity within the cornea. A genetic link seems likely, as the incidence rate is greater if keratoconus or atopic phenotypes have been diagnosed in a family member [2].

The two main problems with keratoconus are the biomechanical instability, which makes it a progressive disease, and irregular astigmatism, which causes it to be a visually incapacitating disease [3].

Treatment modalities are based on refractive correction with spectacles, contact lenses, and intrastromal corneal rings to correct astigmatism and restore visual acuity. Such modalities do not stop ectatic progression and further visual deterioration, which ultimately necessitate corneal transplantation in 10-20% of patients [4].

Corneal collagen cross-linking (CXL) using ultraviolet A light (UVA) and riboflavin was introduced by Wollensak et al. as a method to halt the progression of keratoconus [4]. Its effectiveness relies on a stiffening process of the cornea, as produced in the normal aging process and in patients with diabetes. In the cornea, the interaction of UVA and the photosensitizer riboflavin generates reactive oxygen species inducing chemical covalent bonds bridging amino groups of collagen fibers. This compaction of the stromal collagen layers increases the resistance to deformation, thereby strengthening the cornea against the natural ectatic process of keratoconus. Partial reversing of the keratectasia was also seen in long-term studies showing a flattening effect of the keratometric measurement. Analysis of Scheimpflug imaging further suggests that CXL could help regularize the corneal shape [5].

Scheimpflug imaging is considered among the most prevalent modalities in the diagnosis, staging, and follow-up of keratoconus patients. It is based on a rotating camera and a monochromatic slit-light source, which rotate together. In addition to pachymetry and topographic imaging, Scheimpflug devices provide elevation maps of the anterior and the posterior corneal surfaces [6].

The aim of our study was to evaluate corneal changes after corneal collagen CXL in progressive keratoconus with Pentacam Scheimpflug imaging.


  Materials and methods Top


This study was a prospective interventional study. It was conducted between March 2013 and November 2013 and included 23 eyes of 18 patients with a mean age 23.39 ± 5.83 years (range from 12-33). There were 10 female eyes and 13 male eyes; all underwent corneal collagen CXL using riboflavin and UVA at the Research Institute of Ophthalmology, Giza. Five had both eyes performed. This study was performed in accordance with the ethical standards and informed consent was obtained from all patients.

Inclusion criteria

The inclusion criteria were patients 10-40 years of age suffering from progressive Keratoconus documented in the last 6 months. Patients' corneas should have a clear center with thickness of 400 mm or more.

Exclusion criteria

The exclusion criteria were patients with central or paracentral corneal scars whether epithelial or stromal, a clinical history of herpetic keratitis, evidence of active ophthalmic inflammation, or severe dry eye. Patients with corneal thickness less than 400 mm and patients with previous ocular surgeries were excluded. In addition, patients with autoimmune diseases, those on systemic steroids, and pregnant or lactating women were not included in the study.

Measurements

The following was performed to all patients, preoperatively and 3 and 6 months postoperatively: detailed medical and ophthalmic history, complete ophthalmic examination, and uncorrected and best-corrected visual acuity (BCVA) (both in Snellen lines). Pentacam was used to assess patients' corneal topography and pachymetry. The value of K1 , K2 , thickness at thinnest corneal point, anterior corneal elevation, posterior corneal elevation, cylindrical power and axis, and aberration coefficient were determined.

Operative procedure

All eyes underwent photo-oxidative corneal collagen CXL using riboflavin and UVA light after epithelial debridement of the central 8-9 mm of the cornea. The same CXL machine was used in all cases (Opto Xlink Corneal Cross-Linking System). Riboflavin-UVA corneal collagen CXL was performed without any further intervention throughout the study. Boxer Wachler et al. suggested a modification of the technique by keeping the epithelium intact (epithelium-on or transepithelial CXL). However, finding appropriate means of increasing corneal epithelial permeability before riboflavin application was warranted, as riboflavin has a molecular weight of 338 Da, whereas the corneal epithelium is impermeable to compounds with a molecular weight greater than 100 Da. Accordingly, various approaches have been tried clinically and in the laboratory to enhance the epithelial permeability before the riboflavin application. Chemical enhancers such as benzalkonium chloride, ethylenediamine tetraacetic acid, gentamicin, tetracaine, and 20% ethanol were used, in addition to partial grid-like pattern de-epithelialization, excimer laser superficial epithelial removal, and the replacement of the isotonic by hypotonic riboflavin solution [7].

All cases were conducted under topical anesthesia (Benoxinate HCL drops 0.4%) instilled twice for 2 min before the procedure. After applying the eyelid speculum, epithelium was removed in the central 8-9 mm with a blunt metal spatula. De-epithelialization was followed by instillation of riboflavin (0.1% solution 10 mg riboflavin-5-phosphate in 10 ml dextran-T-500 20% solution) every 5 min for 30 min until the stroma was completely penetrated and the aqueous was stained yellow. The UVA irradiation was performed using an optical system with a light source consisting of an array of UV diodes (370 nm) in conjunction with a potentiometer to allow regulation of voltage. UVA exposure time may be reduced to less than 3 min; this is achieved by increasing the UVA power and reducing the exposure time, thereby maintaining the same energy on the eye as standard CXL while reducing CXL time known as accelerated CXL. During treatment, riboflavin solution was applied every 5 min to ensure saturation. At the end of the procedure, a bandage soft contact lens was kept in place until full corneal re-epithelialization occurred.

The postoperative treatment was a topical combination of steroid and antibiotic drop administered in all patients five times daily for 1 week then tapered to four times/day for the next week then two times/day for the next 2 weeks. If haze appeared, prolonged steroids were used. Lacrimal substitutes (preservative-free artificial tears) were administered four times daily for 4-6 weeks. Five days after the procedure, the contact lens was removed. Three cases had a delayed re-epithelialization and were followed up to full re-epithelialization 2 days later. At 2 weeks follow-up, all cases showed corneal haze, which was expected with the procedure and was resolved at 3-month follow-up visit.

Statistical analysis

All collected data were revised for completeness and accuracy. Precoded data were entered on the computer using the statistical package of social science software program, version 15 to be statistically analyzed. Data were summarized using mean and SD for quantitative variables and number and percent for qualitative variable. Comparison between quantitative variable was performed using paired-samples t-test for variables that were normally distributed. Nonparametric Wilcoxon was used for quantitative variables that were not normally distributed. P value greater than 0.05 indicates not significant; P value less than 0.05 means it is significant; and P value less than 0.01 means it is highly significant.


  Results Top


The mean preoperative uncorrected visual acuity (UCVA) was 0.16 ± 0.2 Snellen line, whereas the mean postoperative UCVA at 3 months was 0.19 ± 0.19 Snellen line. At 6 months, the mean postoperative UCVA was 0.24 ± 0.21 Snellen line with a P value of 0.001 showing a statistically significant improvement from the preoperative value. The mean preoperative BCVA was 0.46 ± 0.19 Snellen line, whereas the mean postoperative BCVA at 3 months was 0.5 ± 0.19 Snellen line. At 6 months, the mean BCVA was 0.63 ± 0.24 Snellen line, thus improving by a mean of 2.0 Snellen lines from the preoperative value with a P value of less than 0.001 showing a statistically significant improvement. [Table 1] shows the visual acuity changes also seen in [Figure 1].
Figure 1: Graph comparing both preoperative and postoperative means UCVA and BSCVA at 3 and 6 months. BCVA, best-corrected visual acuity; UCVA , uncorrected visual acuity.

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Table 1: Visual acuity changes

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The topographic analysis performed by the Pentacam revealed a mean preoperative K1 value of 47.69 ± 4.02 D, whereas the mean postoperative K1 value at 3 months was 47.67 ± 4.33 D. At 6 months, the mean postoperative K1 value was 47.04 ± 4.43 D with a P value of 0.004 showing a statistically significant improvement from before CXL. The mean preoperative K2 value was 51.74 ± 4.76 D, whereas the mean postoperative K2 value at 3 months was 51.29 ± 4.76 D with a P value of 0.004 showing a statistically significant improvement. At 6 months, the mean postoperative K2 value was 51.03 ± 4.92 D with a P value of less than 0.001 showing a statistically significant improvement from before CXL (e.g. [Figure 2]). The mean corneal astigmatism (cylinder) was 4.05 ± 1.81 D, whereas the mean postoperative cylinder at 3 months was 3.61 ± 1.98 D. At 6 months, the mean postoperative cylinder was 3.99 ± 2.13 D. Statistically significant decrease in corneal thinnest location was recorded after 3 months with mean pachymetry (thinnest) of 422.7 ± 34.32 mm and at 6-month post-CXL with a mean pachymetry (thinnest) of 438.35 ± 35.42 mm. The mean preoperative anterior elevation was +34.17 ± 13.61 mm (from best fit sphere), whereas the mean postoperative anterior elevation at 3 months was +33.91 ± 13.97 mm. At 6 months, the mean postoperative elevation front was +30.65 ± 11.11 mm with a P value of 0.006 showing a statistically significant improvement from before CXL. The posterior elevation revealed a mean preoperative value of +74.04 ± 25.71 mm (from best fit sphere), whereas the mean postoperative posterior elevation at 3 months was +75.13 ± 28.39 mm. At 6 months, the mean postoperative posterior elevation was +67.39 ± 23.09 mm with a P value of 0.003 showing a statistically significant improvement from before CXL (e.g. [Figure 3]). The aberrations coefficient was measured by the Pentacam revealing a mean preoperative aberrations coefficient of 2.41 ± 0.64 (ranging from 1.3 to 4.2), whereas the mean postoperative aberrations coefficient at 3 months was 2.42 ± 0.53 (ranging from 1.3 to 3.5). At 6 months, the mean postoperative aberrations coefficient was 2.38 ± 0.63 (ranging from 1.3 to 3.9). [Table 2] shows the Pentacam results.
Figure 2: Pentacam of sagittal curvature front showing K1 and K2 values of the right eye of patient number 17 before cross-linki ng and 3 and 6 months after.

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Figure 3: Pentacam of corneal posterior elevation of the right eye of patient number 15 before cross-linki ng and 3 and 6 months after.

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Table 2: Pentacam changes

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  Discussion Top


In our study, patients showed a statistically significant improvement of the UCVA postoperatively. The mean preoperative UCVA was 0.16 ± 0.2 Snellen line, whereas the mean postoperative UCVA at the last visit (6 months visit) was 0.24 ± 0.21 improving by an average of 1 Snellen lines. In addition, the improvement in the BCVA was highly significant where the mean preoperative BCVA was 0.46 ± 0.19 Snellen line, whereas the mean postoperative BCVA at 6 months visit was 0.63 ± 0.24 Snellen line improving by an average of 2 Snellen lines. Visual improvement was noticed from the third month follow-up visit but was more significant after 6 months from the day of treatment (P < 0.001). Our results are comparable with the results of the study conducted by Kasumovic et al. [1] (28 eyes with average follow-up was 5-12 months) who stated that the UCVA before the operation was 0.12 (0.09-0.32). Three months after CXL, UCVA was 0.1 (range 0.1-0.3). At 6 months, UCVA was 0.2 (range 0.1-0.5). The BCVA of the patients before the treatment was 0.4 (range 0.2-0.6). After 3 months, BCVA was 0.6 (range 0.4-0.8). The BCVA 6 months after CXL was 0.8 (range 0.57-1.0) and was extremely higher than before the intervention (P = 0.003) [1].

Topographic analysis performed for our patients revealed stability with significant flattening of the values of K1 and K2 better seen for K2 after 6 months after CXL. Our results are comparable with the results of the study conducted by Asri et al. [2] (142 eyes with mean follow-up 10 months) showing a mean preoperative flattest K of 47.43 ± 4.09 D. After 3, 6, and 12 months post-CXL, the mean flattest K was 46.20 ± 4.17, 46.66 ± 4.17, and 46.86 ± 4.48 D, respectively. The mean preoperative steepest K was 54.09 ± 6.07 D and the mean postoperative steepest K at 3, 6, and 12 months was 52.62 ± 5.66, 52.96 ± 5.45, and 53.60 ± 5.47 D, respectively. The decrease at 6 and 12 months was statistically significant for both flattest and steepest K values compared with their preoperative respective values [2]. Stability of the corneal cylinder with nonsignificant reduction was noticed comparable with results of the study conducted by Doors et al. [8] (29 eyes) in which the mean topographic astigmatism did not show a significant change compared with before surgery at 1, 3, 6, and 12 months after surgery.

Patients' pachymetry was recorded throughout the study revealing that there was a statistically significant corneal thinning. These initial insignificant changes we think may be attributed to the corneal de-epithelialization that was performed during the operative procedure. Postoperative keratocyte apoptosis and structural changes in corneal collagen fibrils and extracellular matrix may play a pivotal role in corneal thinning after CXL [9]. These results are similar to the study conducted by Caporossi et al. [10], as they also recorded an initial decrease in the pachymetry values of all patients then no statistically significant difference in corneal thickness was observed after 3-month follow-up. The topographic analysis performed by the Pentacam revealed stability with significant reduction of the values of anterior elevation and posterior elevation after 6 months after CXL. Similar to the study by Krαnitz et al. [9] with the difference of the 1-year follow-up, a significant decrease was found (P < 0.001) with the preoperative posterior elevation from 68.33 ± 28.69 to 22.67 ± 16.21 mm after treatment. In contrast to our study, Padmanabhan et al. [3] recorded a significant decrease in the anterior elevation but a significant increase in posterior elevation following CXL. The Pentacam does not show reliability of wavefront aberrations calculated from its corneal shape data; therefore, its use is not recommended in assessing and evaluating ocular aberrations. Pentacam software does generate Zernike coefficients but not in a form that is exportable for analysis. The data acquired were incomplete, and further manual analysis of topographical maps was required. The utility and ease of use of this instrument in assessing wavefront aberrations is questionable. Theoretically, this could be improved through the averaging of several measurements. Further studies are needed to test the practicality of averaging measurements and the implications for reliability. Stabilization, good alignment, and fixed pupil size are essential [11]. In our study, we compared the preoperative and postoperative aberrations using the aberrations coefficient value, which showed minimal nonsignificant reduction from 2.41 ± 0.64 to 2.38 ± 0.63 at 6 months.


  Conclusion Top


To conclude, from our study, we reached an understanding that CXL provides new hope for patients with progressive keratoconus. There is increasing evidence that CXL does not only halt the progression in the keratoconic eye by corneal tissue strengthening, but also improves visual outcomes and corneal shape, which are against the natural course of the disease.

It is the only treatment aimed at the original pathology in these patients; thus, we think it should be performed as a standard treatment for all cases provided following the exclusion criteria mentioned before. As proved by our study, visual acuity and corneal shape still did not reach the normal standards; we thus recommend combining CXL with other procedures such as femtosecond corneal rings insertion or newly arouse topography-guided photorefractive keratectomy with CXL (Athens protocol) according to need. A longer duration of follow-up is recommended for any further studies, which will help to further validate the results.


  Acknowledgements Top


Conflicts of interest

There are no conflicts of interest.

 
  References Top

1.
Kasumovic SS, Pavljasevic S, Dacic-Lepara S, et al. The results of corneal cross-linking in the treatment of keratoconus. Med Arh 2013; 67 :372-373.  Back to cited text no. 1
    
2.
Asri D, Touboul D, Fournié P, et al. Corneal collagen crosslinking in progressive keratoconus: multicenter results from the French National Reference Center for Keratoconus. J Cataract Refract Surg 2011; 37 :2137-2143.  Back to cited text no. 2
    
3.
Padmanabhan P, Radhakrishnan A, Venkataraman AP, et al. Corneal changes following collagen crosslinking and simultaneous topography guided photoablation with collagen cross linking for keratoconus. Indian J Ophthalmol 2014; 62 :229-235.  Back to cited text no. 3
    
4.
Goldich Y, Barkana Y, Wussuku Lior O, et al. Corneal collagen cross-linking for the treatment of progressive keratoconus: 3-year prospective outcome. Can J Ophthalmol 2014; 49 :54-59.  Back to cited text no. 4
    
5.
Legare ME, Iovieno A, Yeung SN, et al. Corneal collagen cross-linking using riboflavin and ultraviolet A for the treatment of mild to moderate keratoconus: 2-year follow-up. Can J Ophthalmol 2013; 48:63-68.  Back to cited text no. 5
    
6.
Labiris G, Giarmoukakis A, Sideroudi H, et al. Variability in Scheimpflug image-derived posterior elevation measurements in keratoconus and collagen-crosslinked corneas. J Cataract Refract Surg 2012; 38 :1616-1625.  Back to cited text no. 6
    
7.
Stojanovic A, Chen X, Jin N, et al. Safety and efficacy of epithelium-on corneal collagen cross-linking using a multifactorial approach to achieve proper stromal riboflavin saturation. J Ophthalmol 2012; 2012 :498435.  Back to cited text no. 7
    
8.
Doors M, Tahzib NG, Eggink FA, et al. Use of anterior segment optical coherence tomography to study corneal changes after collagen cross-linking. Am J Ophthalmol 2009; 148 :844-851.   Back to cited text no. 8
    
9.
Kránitz K, Kovács I, Miháltz K, et al. Corneal changes in progressive keratoconus after cross-linking assessed by Scheimpflug camera. J Refract Surg 2012; 28 :645-649.  Back to cited text no. 9
    
10.
Caporossi A, Mazzotta C, Baiocchi S, et al. Long-term results of riboflavin ultraviolet a corneal collagen crosslinking for keratoconus in Italy: the Siena eyecross study. Am J Ophthalmol 2010; 149 :585-593.  Back to cited text no. 10
    
11.
Shankar H, Taranath D, Santhirathelagan CT, et al. Repeatability of corneal first-surface wavefront aberrations measured with Pentacam corneal topography. J Cataract Refract Surg 2008; 3:727-734.  Back to cited text no. 11
    


    Figures

  [Figure 1], [Figure 2], [Figure 3]
 
 
    Tables

  [Table 1], [Table 2]


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