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ORIGINAL ARTICLE
Year : 2019  |  Volume : 32  |  Issue : 2  |  Page : 698-702

Topography-guided photorefractive keratectomy combined with accelerated corneal collagen cross-linking (The Athens Protocol) for keratoconus


1 Department of Ophthalmology, Faculty of Medicine, Cairo University, Cairo, Egypt
2 Department of Ophthalmology, Faculty of Medicine, Menoufia University, Menoufia, Egypt

Date of Submission14-Oct-2018
Date of Acceptance11-Dec-2018
Date of Web Publication25-Jun-2019

Correspondence Address:
Wagih K Makar
2 Abdellatif Street, Alomranya
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/mmj.mmj_316_18

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  Abstract 

Objective
The aim was to evaluate corneal changes after topography-guided partial photorefractive keratectomy (PRK) combined with accelerated corneal collagen cross-linking (CXL) (the Athens protocol) in progressive keratoconus with Pentacam Scheimpflug imaging.
Background
Keratoconus is a bilateral noninflammatory progressive corneal thinning that results in irregular astigmatism and progressive myopia. Topography-guided partial PRK combined with CXL (The Athens Protocol) has been developed not only to arrest progression of keratoconus but also to offer the patients functional vision.
Patients and methods
This prospective study included 20 eyes that underwent topography-guided partial PRK combined with accelerated CXL (The Athens Protocol). Preoperative and postoperative assessments included visual acuity, slit lamp evaluation, and Pentacam. All investigation and examination were done during the period from June 2017 to June 2018.
Results
All study parameters demonstrated a statistically significant improvement with uncorrected distance visual acuity of 0.55 ± 0.29 Snellen line postoperatively vs. 0.33 ± 0.24 Snellen line preoperatively and best-corrected visual acuity of 0.73 ± 0.25 Snellen line postoperatively vs. 0.61 ± 0.27 Snellen line preoperatively, with a P value of 0.005; flat keratometry of 44.76 ± 1.64 D postoperatively vs. 45.29 ± 2.01 D preoperatively and steep keratometry of 46.55 ± 2.09 D vs. 47.68 ± 2.42 D, preoperatively, with a P value of less than 0.001; mean postoperative index of surface variance of 50.70 ± 18.34 postoperatively vs. 65.25 ± 29.29 preoperatively, with P value less than 0.001; and mean postoperative index of height decentration of 0.053 ± 0.033 postoperatively vs. 0.091 ± 0.052 preoperatively, with P value less than 0.001.
Conclusion
Topography-guided partial PRK combined with accelerated CXL (The Athens Protocol) is a relatively new and revolutionary procedure aimed at stabilization of corneal ectatic disorders and achieving a good visual quality. Longer duration of follow-up and a larger sample may further provide more reliable results.

Keywords: astigmatism, Athens protocol, keratoconus, keratometry, pentacam


How to cite this article:
Makar WK, Marey HM, Khairy HA. Topography-guided photorefractive keratectomy combined with accelerated corneal collagen cross-linking (The Athens Protocol) for keratoconus. Menoufia Med J 2019;32:698-702

How to cite this URL:
Makar WK, Marey HM, Khairy HA. Topography-guided photorefractive keratectomy combined with accelerated corneal collagen cross-linking (The Athens Protocol) for keratoconus. Menoufia Med J [serial online] 2019 [cited 2019 Sep 17];32:698-702. Available from: http://www.mmj.eg.net/text.asp?2019/32/2/698/260892




  Introduction Top


Keratoconus is a bilateral noninflammatory progressive corneal thinning that is often of unknown etiology and is characterized by steepening and paracentral reduction of biomechanical strength of the cornea and stromal thinning which results in irregular astigmatism and progressive myopia, and this eventually leads to a decrease in visual acuity[1]. Reported prevalence in the general population varies from 50–200 cases per 100 000 population. It is commonly an isolated ocular condition but sometimes coexists with other ocular and systemic diseases[2]. The maximal progression of keratoconus occurs during the second and third decades of life. Young patients are at risk for faster disease progression, and corneal grafting often becomes necessary for visual rehabilitation[3].

The current mainstream therapy is the use of spectacles and rigid contact lenses, with penetrating keratoplasty reserved for advanced cases or contact lens intolerance[4]. However, corneal transplantation is an expensive procedure with many complications such as high astigmatism and graft rejection; hence, seeking for a way to halt this progressive disease seems to be of crucial importance[5]. Corneal collagen cross-linking (CXL, X-linking) is a recently introduced treatment for addressing progressive keratoconus. CXL is a low-invasive procedure designed to strengthen the corneal structure and stop the progression of keratoconus[6]. In recent times, evidence has shown that collagen CXL with riboflavin drops increases the biomechanical strength and stability of the cornea[7]. In this procedure on the cornea, additional cross-links can be induced within or between the collagen fibers using ultraviolet A (UVA) light and the photomediator riboflavin[8]. The efficacy and safety of the procedure were confirmed in numerous clinical trials[6],[9]. Several clinical studies have demonstrated that CXL effectively slows keratoconus progression in adult eyes. Therefore, CXL could potentially reduce the need for corneal grafting in these young individuals[10]. Topography-guided partial photorefractive keratectomy (PRK) combined with collagen CXL (The Athens Protocol) is a relatively new technique in the management of keratoconus, which performs the topography-guided partial PRK, and then does the CXL procedure. The excimer laser ablation resembles that employed in a hyperopic treatment. Laser energy is applied using a 5.5-mm effective optical zone, and it targets the steepening of the area adjacent to the cone in an attempt to normalize the corneal surface[11]. In support of the rationale for performing the two procedures simultaneously with the ablation first, data have shown that the corneal epithelium and Bowman membrane can act as barriers to the penetration of UVA light into the stroma[12]. Because in the Athens Protocol we remove the epithelium and Bowman membrane, it seems intuitive that the efficacy of the CXL procedure would increase. This concept is supported by clinical findings[13]. The aim of this study was to evaluate corneal changes after the Athens protocol in progressive keratoconus with Pentacam Scheimpflug imaging.


  Patients and Methods Top


This study is a prospective interventional study. It was done between June 2017 and June 2018 and included 20 eyes of 15 patients of age ranging from 19 to 35 years. They all underwent topography-guided partial PRK combined with corneal accelerated collagen CXL (The Athens Protocol). Five patients had both their eyes done. All investigations and examinations were done from June 2017 to June 2018. The study was approved by the scientific ethical committee of Menoufia Medical School, and the patients signed written consent after they were informed about the nature of the study.

Inclusion criteria were patients aging above 18 years old with mild to moderate keratoconus, with minimal corneal thickness more than 400 μm. Exclusion criteria were any ocular pathology, a history of herpetic keratitis, severe dry eye, concurrent corneal infections, concomitant autoimmune diseases, patients with central or paracentral opacities, corneal thickness of less than 400 μm at the thinnest point, and any previous ocular surgeries.

Preoperative evaluation for detailed medical and ophthalmic history was done for all patients, followed by complete ophthalmic examination, including uncorrected and best-corrected visual acuity, anterior segment examination by slit lamp biomicroscopy, and posterior segment examination using +90 diopters lens for slit lamp fundus biomicroscopy. Follow-up was done at 5 days, and at 3 months postoperatively, and all patients were assessed postoperatively for objective refraction using the Topcon (Topcon corp., Tokyo, Japan) automated refractometer which was then confirmed by trial. Scheimpflug Camera (A Wavelight Allegro Oculyzer, Alcon, Texas, USA) Pentacam was used to assess patients' corneal topography and pachymetry, and the value of K1 and K2 were assessed. Thickness at the corneal center and at the thinnest corneal point, together with anterior surface indices [index of surface variance (ISV), index of height decentration (IHD)], and cylindrical power at the cornea front were all determined.

Operative procedure

The procedure is performed under sterile conditions in the operating room. The technique is performed under topical anesthesia and then a speculum is put to keep the eye open. A ring is placed over the treatment zone and 20% alcohol solution is applied for 30 s and then removal of corneal epithelium is done using a blunt spatula. Topography-guided PRK was done by Alcon/WaveLight EX500 excimer laser. The software uses data from eight topographies from Topolyzer and averages the data. Thus it enables the surgeon to adjust the desired postoperative corneal asphericity. The software also provides the option of including tilt correction. 'No Tilt' option was chosen in all cases. Once the adjustment of sphere, cylinder and axis was done, the treatment zone was kept at 5.5 mm in all cases with maximum ablation depth 50 μm. Riboflavin eye drops 0.1% are applied to exposed stromal surface for 10 min before exposing the corneal stromal surface to UVA radiation (370 nm) using Avedro Kxl CrossLinking System at radiance of 30 mW/cm2 for 8 min.

Statistical analysis was done using the statistical package for social sciences, version 20.0 (SPSS Inc., Chicago, Illinois, USA). Quantitative data were expressed as mean ± SD. Qualitative data were expressed as frequency and percentage. The following tests were done. Paired sample t-test of significance was used when comparing between related sample. The confidence interval was set to 95% and the margin of error accepted was set to 5%. So, the P value was considered significant as the following: P value less than 0.05 was considered significant, P value less than 0.001 was considered as highly significant, P value greater than 0.05 was considered insignificant.


  Results Top


This is a prospective consecutive interventional study carried out on 20 eyes of 15 patients, with eight female and seven male patients. Five patients had both their eyes done, with a mean age 27.73 ± 5.12 years (range: 19–35 years). All eyes underwent underwent topography-guided partial PRK combined with collagen CXL (The Athens Protocol).

The mean preoperative uncorrected visual acuity (UCVA) was 0.33 ± 0.24 Snellen line (decimal), whereas the mean postoperative UCVA was 0.55 ± 0.29 Snellen line, with a P value of less than 0.001, showing statistically highly significant improvement from the preoperative value. The mean preoperative best-corrected visual acuity (BCVA) was 0.61 ± 0.27 Snellen line (decimal) whereas the mean postoperative BCVA was 0.73 ± 0.25 Snellen line, with a P value of 0.005, showing statistically significant improvement from the preoperative value [Table 1].
Table 1: The changes in UCVA and BCVA and its significance

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The mean preoperative spherical equivalent was −2.89 ± 1.55, whereas the mean postoperative spherical equivalent was −1.09 ± 0.84, with a P value of less than 0.001, which is statistically highly significant.

The mean preoperative K1 value of 45.29 ± 2.01 D, whereas the mean postoperative K1 value was 44.76 ± 1.64 D, with a P value of 0.046* showing a statistically significant improvement. The mean preoperative K2 value was 47.68 ± 2.42 D whereas the mean postoperative K2 value was 46.55 ± 2.09 D, with a P value of less than 0.001, showing a statistically highly significant improvement. The mean preoperative Kmax value of 52.66 ± 4.20 D whereas the mean postoperative Kmax value was 48.55 ± 2.74 D, with a P value of less than 0.001, showing a statistically highly significant improvement [Table 2].
Table 2: The changes in anterior keratometric values and its significance

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A preoperative mean corneal astigmatism (cylinder) was 2.37 ± 1.38 D, whereas the mean postoperative cylinder was 1.76 ± 0.99 D, with P value of 0.011, which is statistically significant.

Anterior surface topometric indices changes by pentacam image were as follows: a preoperative mean ISV was 65.25 ± 29.29, whereas the mean postoperative ISV was 50.70 ± 18.34, with P value less than 0.001, which is statistically highly significant. A preoperative mean IHD was 0.091 ± 0.052, whereas the mean postoperative IHD was 0.053 ± 0.033, with P value less than 0.001, which is statistically highly significant [Table 3].
Table 3: The changes in anterior surface topometric indices and its significance

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The corneal pachymetry at thinnest point was measured by the Pentacam, and statistical analysis revealed a mean preoperative pachymetry (thinnest) of 480.55 ± 37.22 μm. A statistically significant decrease in corneal thinnest location was recorded with mean pachymetry (thinnest) of 441.45 ± 44.86 μm, with P value less than 0.001.


  Discussion Top


The goal in the treatment of keratoconus consists of two parameters: corneal biomechanical stability and improving optical inefficiency owing to irregular cornea. The goal of this study is treating keratoconic patients and offer them both stability and functional vision. Corneal collagen cross-linking (CXL) alone aims only to stop the progression of keratoconus by increasing the number of CXL sites within the collagen molecule after collagen CXL, stiffer fibrils and lamellae are generated so improve corneal biomechanical strength[14]. The application of excimer laser surface ablation has been introduced formerly for the correction of stable or forme fruste keratoconus despite being a tissue-removing procedure. Alpins and Stamatelatos[15] reported a prospective case series of 32 eyes treated with customized photoastigmatic refractive keratectomy and followed up for up to 10 years with no evidence of keratoconic progression. In this study when doing simultaneous topography-guided partial PRK with corneal CXL, we aim to arrest progression by CXL and at the same time normalize the irregular corneal surface and thus help to give the patients functional vision. In this study, patients showed a statistically highly significant improvement of the UCVA and BCVA postoperatively. These visual rehabilitation improvements appear to be superior to those reported in cases of simple CXL treatment[16].

The results of our study were comparable with the results of the study conducted by Kymionis et al.[17] (14 eyes with mean follow-up of 10.69 ± 5.95 months range: 3–16 months) which also show significant improvement of UCVA and BCVA. Topographic analysis done for our patients preoperatively by pentacam revealed statistically significant improvement of keratometric values. Sakla et al.[18] conducted a study on 85 eyes with mean follow up 12 months. It showed also improvement of keratometric values. The two anterior surface indices, ISV and IHD, also demonstrated postoperative improvement. A smaller value is indication of corneal normalization (lower ISV, less irregular surface, lower IHD, cone less steep and more central). Such changes have been reported by Kanellopoulos and Asimellis[13]. Moreover, patients' pachymetry was recorded throughout the study using the pentacam and as expected by the fact that Athens Protocol includes a partial stromal excimer ablation, and there is reduction of postoperative corneal thickness, manifested by the thinnest corneal thickness. So that PRK treatment was planned based on the patients' corneal thickness. Restricted treatments of up to 50 mm were performed, whereas the ablation depth was mapped out by modifying the target correction in a limited fashion to remove the least possible amount of tissue. Undercorrection of sphere and cylinder was planned and the amount of customization also was adjusted[19]. However, despite the thinnest corneal thickness decreased as a result of excimer laser ablation, there is stabilization over time without additional thinning[13].


  Conclusion Top


KC is a bilateral, noninflammatory, progressive disorder characterized by corneal thinning and protrusion that induces myopia and myopic astigmatism. Combined topography-guided partial PRK with CXL (The Athens Protocol) is a relatively new, revolutionary, minimally invasive procedure aiming at the stabilization of corneal ectatic disorders and achieving a good visual quality. Scheimpflug imaging is considered among the most prevalent modalities in the diagnosis, staging, and follow-up of keratoconus patients. Our results revealed that 3 months postoperatively, the Athens Protocol appeared to be effective, not only in halting the progression of KC but also in improving uncorrected and best-corrected visual acuities by normalization of the corneal surface and decrease in irregular astigmatism. This was seen in the flattening effect of the keratometric measurements and the improvement in the anterior surface topometric indices. So we recommend that combined topography-guided partial PRK with CXL (The Athens Protocol) should become a standard treatment for progressive KC. Longer duration of follow up and a larger sample may further provide more reliable results.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Vazirani J, Basu S. Keratoconus: current perspectives. Clin Ophthalmol 2013; 7:2019–2030.  Back to cited text no. 1
    
2.
Woodward MA, Blachley TS, Stein JD. The association between sociodemographic factors, common systemic diseases, and keratoconus: an analysis of a Nationwide Heath Care Claims Database. Ophthalmology 2016; 123:457–465.  Back to cited text no. 2
    
3.
Gordon-Shaag A, Millodot M, Shneor E. The epidemiology and etiology of keratoconus. Int J Keratoco Ectatic Corneal Dis 2012; 1:7–15.  Back to cited text no. 3
    
4.
Wollensak G, Spoerl E, Seiler T. Riboflavin/ultraviolet-a induced collagen crosslinking for the treatment of keratoconus. Am J Ophthalmol 2003; 135:620–627.  Back to cited text no. 4
    
5.
Thompson Jr RW, Price MO, Bowers PJ, Price Jr FW. Long-term graft survival after penetrating keratoplasty. Ophthalmology 2003; 110:1396–1402.  Back to cited text no. 5
    
6.
Raiskup F, Spoerl E. Corneal crosslinking with riboflavin and ultraviolet A. Part II. clinical indications and results. Ocular Surface 2013; 11:93–108.  Back to cited text no. 6
    
7.
Sharma A, Nottage JM, Mirchia K, Sharma R, Mohan K, Nirankari VS. Persistent corneal edema after collagen cross-linking for keratoconus. Am J Ophthalmol 2012; 154:922–926.  Back to cited text no. 7
    
8.
Hafezi F, Mrochen M, Iseli HP, Seiler T. Collagen cross-linking with ultraviolet A and hypo-osmolar riboflavin solution in thin corneas. J Cataract Refract Surg 2009; 35:621–624.  Back to cited text no. 8
    
9.
Wollensak G. Corneal collagen cross-linking: new horizons. Expert Rev Ophthalmol 2010; 5:201–215.  Back to cited text no. 9
    
10.
Viswanathan D, Males J. Prospective longitudinal study of corneal collagen cross-linking in progressive keratoconus. Clin Exp Ophthalmol 2013; 41:531–536.  Back to cited text no. 10
    
11.
Krueger RR, Kanellopoulos AJ. Stability of simultaneous topography-guided photorefractive keratectomy andriboflavin/UVA cross-linking for progressive keratoconus: case reports. J Refract Surg 2010; 26:S827–S832.  Back to cited text no. 11
    
12.
Kolozsavari L, Nogradi A, Hopp B, Bor Z. UV absorbance of the human cornea in the 240- to 400-nm range. Invest Ophthalmol Vis Sci 2002; 43:2165–2168.  Back to cited text no. 12
    
13.
Kanellopoulos AJ, Asimellis G. Keratoconus management: long-term stability of topography-guided normalization combined with high-fluence CXL stabilization (the Athens Protocol). J Refract Surg 2014; 30:88–93.  Back to cited text no. 13
    
14.
Kasumovic S, Pavljasevic S, Dacic-Lepara S, Jankov M. The results of corneal cross-linking in the treatment of keratoconus. Med Arh 2013; 67:372–373.  Back to cited text no. 14
    
15.
Alpins N, Stamatelatos G. Customized photoastigmatic 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. 15
    
16.
Legare ME, Iovieno A, Yeung SN, Kim P, Lichtinger A, Hollands S, 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. 16
    
17.
Kymionis GD, Kontadakis GA, Kounis GA, Portaliou DM, Karavitaki AE, Magarakis M, et al. Simultaneous topography-guided PRK followed by corneal collagen cross-linking for keratoconus. J Refract Surg 2009; 25:S807–S811.  Back to cited text no. 17
    
18.
Sakla H, Altroudi W, Munoz G, Sakla Y. Simultaneous topography-guided photorefractive keratectomy and accelerated corneal collagen cross-linking for keratoconus. Cornea 2016; 35:941–945.  Back to cited text no. 18
    
19.
Kontadakis GA, Vardhaman P, Kankariya VP, Konstantinos T, Aristofanis I, Pallikaris AI, et al. Long-term comparison of simultaneous topography-guided photorefractive keratectomy followed by corneal cross-linking versus corneal cross-linking alone. Ophthalmology 2016; 123:974–983.  Back to cited text no. 19
    



 
 
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