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ORIGINAL ARTICLE
Year : 2020  |  Volume : 33  |  Issue : 4  |  Page : 1195-1200

High-order aberration changes after corneal collagen cross-linking for keratoconus


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

Date of Submission22-Apr-2020
Date of Decision14-May-2020
Date of Acceptance31-May-2020
Date of Web Publication24-Dec-2020

Correspondence Address:
Mahmoud A. E. R. M. Ibrahim
Zagazig
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/mmj.mmj_118_20

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  Abstract 


Objective
The aim was to determine the changes in the ocular high-order aberrations (HOAs) after corneal cross-linking (CXL) in patients with keratoconus and its correlation with the changes in visual acuity (VA).
Background
HOAs are among the important refractive and visual quality properties of the human ocular system, and the decreased levels of some visual features such as contrast sensitivity have been partially attributed to these parameters. Evaluation of long-term changes of HOAs after CXL is useful in understanding the efficacy of CXL on improving optical, refractive, and VA.
Patients and methods
All patients were subjected to preoperative and postoperative assessment for best-corrected VA, anterior segment examination (cornea, iris, and lens), posterior segment examination (vitreous and retina), corneal topography, and HOA using Oculus Pentacam II.
Results
Regarding coma and trefoil aberrations, there was a statistically insignificant difference preoperatively and postoperatively in both eyes, as P value was more than 0.05. The total HOAs were statistically significant preoperatively and postoperatively, as P value was less than 0.05.
Conclusion
Total HOAs and keratometric readings significantly decreased after CXL. Ocular aberrations play a key role in influencing retinal image quality. Correcting HOAs in patients with keratoconus is likely to improve the quality of vision significantly.

Keywords: corneal cross-linking, high-order aberrations, keratoconus


How to cite this article:
Khairy HA, Basiony AI, Ibrahim MA. High-order aberration changes after corneal collagen cross-linking for keratoconus. Menoufia Med J 2020;33:1195-200

How to cite this URL:
Khairy HA, Basiony AI, Ibrahim MA. High-order aberration changes after corneal collagen cross-linking for keratoconus. Menoufia Med J [serial online] 2020 [cited 2024 Mar 28];33:1195-200. Available from: http://www.mmj.eg.net/text.asp?2020/33/4/1195/304478




  Introduction Top


Keratoconus (KC) is a noninflammatory progressive central or paracentral corneal thinning, leading to irregular astigmatism, progressive myopia, and increased high-order aberrations (HOAs), with consequent impaired visual function[1].

Decrease in keratocyte density, reduction in the number of lamellae, and a degradation of fibroblasts in KC corneal stroma lead to the reduction in the corneal thickness and biomechanical strength[2].

The diagnosis of KC is typically made on the basis of a combination of clinical signs, corneal topographic, and tomographic signs. The KC topographic patterns differ qualitatively and quantitatively from those of normal corneas. Combination of topography and wave front analysis may help define keratoconic subtypes and increase the sensitivity and specificity for early detection of subclinical KC[3].

Corneal collagen cross-linking (CXL) has emerged as a promising management option for KC. In CXL, the interaction of ultraviolet-A (UVA, 365 nm) and riboflavin 0.1% in 20% dextran solution (Ricrolin, Sooft Italia S.p.A., Montegirorgio, Italy), which acts as a photomediator that increases UVA light absorption within the corneal stroma, leads to cross-linking within the collagen and intracellular matrix of the stroma and results in an increase in the formation of covalent intrafibrillar and interfibrillar bonds by photosensitized oxidation, most predominantly in the anterior 300 mm, resulting in the strengthening of the cornea[4].

HOAs can be a valuable diagnostic tool in detecting subtle disorders of the cornea or lens and for grading the severity of KC. The magnitude of total HOA, vertical coma, is significantly higher in KC than in normal eyes. The combination of cone sizes, location, and an irregular shape results in the occurrence of worst, visually significant HOAs[5].

Increased corneal HOAs and ocular HOAs are sequelae of KC that contribute to the diminished visual function. The most common and potentially disruptive HOAs are spherical aberration and coma. As KC progresses, the cone bulges anteriorly and the cornea thins and steepens and becomes more prolate, which explain why the spherical aberration becomes more negative. Spherical aberration creates halos around points of light, whereas coma makes points of light appear like a comet[6].

The aim of this study was to determine the changes in the ocular HOAs after CXL in patients with KC and its correlation with the changes in visual acuity (VA).


  Patients and Methods Top


This prospective case serial study involved 50 patients with KC, comprising 30 patients bilaterally and 20 patients unilaterally. The study was carried out in ophthalmology outpatient clinic of private center (Al Rowad LASIK Center) in a period from May 2019 to December 2019 and were treated with CXL by accelerated type (AVEDRO) and followed for 3 months.

Approval of the Institutional Review Board was taken before the study, and written consent was taken from every patient before participating in the study.

Inclusion criteria

Keratoconic patients with central corneal thickness greater than or equal to 400 μ were included.

Exclusion criteria

Patients with previous herpetic keratitis; patients with active ophthalmic diseases such as infection, uveitis, etc.; patients with any previous ocular operations; and patients with corneal opacities or scars were excluded.

Preoperative assessment

A baseline ophthalmic examination was performed on all eyes, which included slit lamp biomicroscopy, ultrasonic corneal pachymetry, and simultaneous measurement of corneal tomography, Scheimpflug camera-based corneal topography (Pentacam ALLEGRO oculyzer version 1074; Wave Light AG, Erlangen, Germany), and wave front aberrometry. The iTrace was used to evaluate HOA and refractions. VA was determined using Snellen charts. For the purpose of statistical analysis, the Snellen VA was converted to the corresponding logarithm of the minimum angle of resolution (log MAR) value using standard conversion tables.

Operative technique

CXL was performed under topical anesthesia (Benoxinate HCL drops 0.4%) instilled twice for 2 min before the procedure. Routine sterile conditions were followed in OR. Povidone iodine 10% was used for skin disinfection, with lid speculum inserted. Epithelium-off technique was used, and under operating microscope, the central 8–9 mm of the corneal epithelium was debrided with a hockey knife to enable adequate stromal riboflavin absorption. Instillation of riboflavin (0.1% solution 10 mg riboflavin-5-phosphate in 10 ml dextran-T-500 20% solution) was done every 5 min for 30 min until the stroma was completely penetrated, and a yellow coloration was seen in the anterior chamber on slit lamp biomicroscopy. The central 8–9 mm of the cornea was irradiated with UVA (370 nm), at 3 mW/cm2 for 30 min. Irrigation of the ocular surface with balanced salt solution was performed. At the end of the procedure, a bandage on soft contact lens was kept in place until full corneal re-epithelialization occurred.

Topical steroid (prednisolone acetate 1% eye drops) and antibiotic (moxifloxacin 0.5% eye drops) four times daily for 1 week were initiated, and then antibiotic drops were stopped. Steroid was tapered to three times/day for the next week and then two times/day for the next 2 weeks. Lacrimal substitutes (preservative-free artificial tears) were administered four times daily for 4–6 weeks.

Statistical analysis

The collected data were coded, entered, presented, and analyzed by computer using a data base software program, Statistical Package for the Social Sciences version 20 (SPSS Inc., Chicago, Illinois, USA). Qualitative data were represented as frequencies and percentage. For quantitative variables, mean, and SD were computed. χ2 or Fisher tests were used to detect relation between different qualitative variables. Sensitivity, specificity, predictive value for positive, predictive value for negative, and accuracy were calculated at 95% confidence interval to measure the validity.


  Results Top


The present study was carried on 80 eyes of 50 keratoconic patients, including 30 patients bilaterally and 20 patients unilaterally. There were 30 (60%) males and 20 (40%) females. Patients age ranged from 15 to 45 years, with a mean age of 27.72 ± 6.71 years. They were treated with CXL by accelerated type (AVEDRO) and followed up for 3 months [Figure 1].
Figure 1: (a) Changes of coma aberrations pre and postoperatively; (b) comparison between per-CXL and post-CXL according to trefoil aberrations; (c) changes in spherical aberrations preoperative and postoperative; (d) comparison between preoperative and postoperative HOAs in both eyes. CXL, corneal cross-linking; HOA, high-order aberration.

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There was no statistically significant difference preoperatively and postoperatively in right eye regarding K1, as P value was 0.094, whereas there was a significant difference regarding K1 in left eye, as P value 0.027. Preoperatively, K1 mean in right eye was 45.2 ± 3.04 (range = 40–58.4), whereas postoperatively, it was 44.03 ± 2.82 (range = 39–54.3). In left eye, K1 mean was 45.73 ± 4.92 (range = 34.9–63) preoperatively, whereas postoperatively the mean was 43.77 ± 2.11 (range = 39.8–49.2). Preoperatively, K2 mean value in right eye was 48.24 ± 4.65 (range = 41.2–61.9). There was a statistically significant difference preoperatively and postoperatively, as P value was 0.047 (<0.05). In left eye, K2 mean value was 49.21 ± 5 preoperatively, whereas postoperatively it was 46.96 ± 2.43. There was a statistically significant difference in K2 value preoperatively and postoperatively, as P vale was 0.018. There was no statistically significant difference regarding Kmax in both eyes preoperatively and postoperatively, as P value greater than 0.05. In right eye, Kmax mean value was 53.63 ± 6.35 preoperatively, whereas it was 51.44 ± 5.94 postoperatively. In left eye, the mean value of Kmax was 54.43 ± 8.31 preoperatively and it was 52.34 ± 5.27 postoperatively [Table 1].
Table 1: Keratometric changes preoperatively and postoperatively

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Regarding coma aberrations, there was no statistically significant difference preoperatively and postoperatively in both eyes, as P value greater than 0.05. In right eye, KA mean value was 5.61 ± 3.21 preoperative, whereas it was 1.48 ± 1.09 postoperatively. In left eye, the mean value was 2.30 ± 1.81 preoperatively and 2.07 ± 1.80 postoperatively. Regarding trefoil aberrations, there was no statistically significant difference preoperatively and postoperatively, as P value was greater than 0.05. Preoperatively, the mean value of T A in right eye was 0.42 ± 0.39, whereas postoperatively, it was reduced to 0.41 ± 0.33. In left eye, the mean value was 0.66 ± 0.76 preoperatively, whereas it was reduced to 0.84 ± 1.37 postoperatively. Preoperatively, SA mean value was 0.43 ± 0.37 in right eye, whereas postoperatively, it decreased to 0.44 ± 0.41. In left eye, SA mean value was 0.55 ± 0.74 preoperatively and decreased to 0.41 ± 0.34 postoperatively. There was no statistically significant difference in both eyes, as P value was greater than 0.05 [Table 2].
Table 2: Aberrometric changes in both eyes preoperatively and postoperatively

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Regarding the preoperative and postoperative changes in aberrometry, in right eye, the mean value was 0.30 ± 0.35 preoperatively, whereas it became 0.33 ± 0.39 postoperative. In left eye, mean value was 0.33 ± 0.27 preoperative and decreased to 0.31 ± 0.3 postoperatively. There was no statistically significant difference in both eyes, as P value was greater than 0.05. Regarding the total high-HOAs, there was a statistically significant difference preoperatively and postoperatively in both eyes, as P value was less than 0.05. In right eye, HOA mean value was 107.07 ± 8.92 preoperatively and decreased to 102.97 ± 6.60 postoperatively. In left eye, mean value was 108.56 ± 11.12 preoperatively and decreased to 103 ± 4.83 postoperatively [Table 3].
Table 3: Aberrometric changes in both eyes preoperatively and postoperatively

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Regarding VA; in right eye, the mean uncorrected visual acuity (UCVA) was 0.11 ± 0.06 preoperatively, whereas it was 0.12 ± 0.05 postoperatively. In left eye, mean value was 0.08 ± 0.06 and increased to become 0.11 ± 0.06 postoperatively. There was no statistically significant difference preoperatively and postoperatively, as P value was greater than 0.05. The mean best-corrected visual acuity (BCVA) preoperatively was 0.40 ± 0.12 in right eye and changed to be 0.44 ± 0.14 postoperatively. In left eye, the mean value was 0.36 ± 0.13 preoperative and changed to be 0.41 ± 0.14 postoperatively. There was no statistically significant difference preoperatively and postoperatively in both eyes, as P value was greater than 0.05 [Table 4].
Table 4: UCVA and BCVA variation preoperatively and postoperatively in both eyes

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  Discussion Top


The primary goal of CXL is the stabilization of KC. Astigmatism treatment, increase of VA, and better vision quality are also the secondary goals. Riboflavin/UVA application induces collagen cross-linking for the treatment of KC[7].

In this study, which aimed to determine the changes in the corneal and ocular HOA after CXL as measured by the Pentacam, there were changes in HOAs that were correlated with the changes in VA. The results of the present work were obtained from the same patients before and 3 months after surgery. VA was used clinically for assessing the effect of HOAs. Increased levels of HOAs introduced by KC lead to reduced VA.

Conversely, correcting HOAs by CXL can improve VA. MAR varied linearly with the magnitude (RMS) of all modes of aberration. Not all HOAs have the same ability to degrade vision; the effect of individual Zernike lower and HOAs varied significantly with mode.

In our study, there was a statistically significant reduction in mean K1 reading in left eyes and k2 readings in both eyes. The preoperative mean K1 was 45.73 ± 4.92 (range: 34.9–63), whereas postoperatively the mean was 43.77 ± 2.11. Preoperatively, k2 mean value in right eye was 48.24 ± 4.65 (range = 41.2–61.9). There was a statistically significant difference preoperatively and postoperatively, as P value was 0.047 (<0.05). In left eye, k2 mean value was 49.21 ± 5 preoperatively, whereas postoperatively it was 46.96 ± 2.43. There was a statistically significant difference in k2 value preoperatively and postoperatively, as P value was 0.018.

These results were comparable with the results obtained by Caporossi et al.[8], who recorded topographic mean reduction in dioptric power of 2.1 ± 0.13 D.

Another study in 2008 conducted by Raiskup-Wolf et al.[9] reported that the improvement in vision after cross-linking is caused by a decrease in corneal curvature and by topographical homogenization of the cornea as a result of the increased rigidity in the cross-linked cornea. Initial worsening of keratometric readings observed by the study by Mazzotta et al.[8] in 2011 in the first month may be owing to transient haze and corneal edema.

In contrast, there was a statistically insignificant difference in k1 in right eyes and k max in both eyes. Preoperatively, k1 mean was 45.2 ± 3.04 (range = 40–58.4), whereas postoperatively, it is 44.03 ± 2.82.

Our findings were supported by Vinciguerra et al.[10], who suggested that it may be, in part, owing to the epithelial layer being thickest around the cone and thinnest at its apex, masking the underlying steepness. Immediately after the removal of epithelium, they found that the steepest K reading changed from a mean of 58.82–61.05 D.

The present study revealed that there was a statistically insignificant corneal thinning with little reduction in corneal thickness postoperatively. These initial changes may be attributed to the corneal de-epithelialization that was performed during the CXL procedure, postoperative keratocyte apoptosis, and structural changes in corneal collagen fibrils and extracellular matrix in the anterior stroma.

Reduced corneal thickness may also be explained by the increase in endothelial pump activity or density induced by the treatment. The corneal thickness gradually increased after the first month of treatment, and this increasing value did not reach the preoperative reading by the end of 3 months of follow-up.

Our data were agreed with the results of a study in 2017 conducted by Greenstein et al.[11] who found that there was a statistically significant corneal thinning. These initial changes may be attributed to the corneal de-epithelialization that was performed during the CXL procedure, postoperative keratocyte apoptosis, and structural changes in corneal collagen fibrils and extracellular matrix in the anterior stroma (250–300 mm).

In our study, the total HOAs were statistically significantly different preoperatively and postoperatively, as P value was less than 0.05. In right eye, HOA mean value was 107.07 ± 8.92 preoperative and decreased to 102.97 ± 6.60 postoperative. In left eye, mean value was 108.56 ± 11.12 preoperatively and decreased to 103 ± 4.83 postoperatively.

Previous reports mentioned significant improvement in total and corneal aberrations such as total coma and spherical aberration. In 2008, a study by Vinciguerra et al.[10] reported a significant decrease in total aberrations, a reduction in all corneal aberrations up to the seventh order, and a significant decrease in coma which are the dominant HOAs in KC after CXL.

It is believed that the cornea assumes a more regular shape after CXL. Similar observations were reported in a study by Mazzotta et al.[8], who found a statistically significant reduction in the total corneal HOA and coma aberration, starting early after treatment and increasing for up to 24 months in 44 eyes.

Our study were not consistent with Greenstein et al.[11], who reported that the changes in HOAs were not statistically correlated with improvements in VA, despite significant improvements in vision, topography, and wave front measures after CXL, as there is a high variability in objective measurements in the KC, as well as differing lengths of follow-up.

In 2017 a study conducted by El-Massry et al.[12] on 30 eyes of 16 patients revealed that total HOAs and total coma were statistically significantly reduced at 6 months by 25% and 18%, respectively. The RMS of total HOAs was 2.05 ± 1.55 μm, and 6 months later, it had reduced to 1.36 ± 1.25 μm (P = 0.001), whereas the RMS of total coma aberrations was 1.72 ± 1.38 μm, and 6 months later, it had reduced to 1.11 ± 1.01 μm (P = 0.001). Significant improvement was seen in spherical aberration (P = 0.001), whereas no significant change was observed in trefoil and astigmatism (P = 0.405 and 0.329, respectively).

Our study revealed that there was a statistically insignificant difference in the UCVA and BCVA but there is an improvement postoperatively in mean readings. Regarding the mean preoperative UCVA, in right eye, the mean value was 0.11 ± 0.06 preoperative, whereas it was 0.12 ± 0.05 postoperatively. In left eye, mean value was 0.08 ± 0.06 and increased to become 0.11 ± 0.06 postoperatively. There was a statistically insignificant difference preoperatively and postoperatively, as P value was greater than 0.05. The mean value of BCVA preoperatively was 0.40 ± 0.12 in right eye and changed to be 0.44 ± 0.14 postoperatively. In left eye, the mean value was 0.36 ± 0.13 preoperatively and changed to be 0.41 ± 0.14 postoperatively. There was no statistically significant difference preoperatively and postoperatively in both eyes, as P value was greater than 0.05.

In 2011, Derakhshan et al.[13] have published their observational study on the effect of cross-linking as primary treatment for patients with early KC, with mean follow-up of 6 months. Their results show significant improvement in UCVA and BCVA, and reduction in SE and keratometric readings. Visual improvement in most patients began after the first month, slightly increased by the third month, and remained stable until 6 months.

Similarly, in 2009, Vinciguerra et al.[10] found that in patients with KC, mean best-corrected vision (log MAR) improved from 0.28 to 0.14 at 12 months postoperatively. Moreover, in 2011, Raiskup-Wolf et al.[9] and Caporossi et al.[8] reported significant improvements in CDVA, with continued improvement after 1-year follow-up. They noticed a trend toward a more regular cornea.


  Conclusion Top


Total HOAs and keratometric readings significantly decreased after CXL. Ocular aberrations play a key role in influencing retinal image quality. Correcting HOAs in patients with KC is likely to improve the quality of vision significantly. Evaluation of long-term changes of HOAs after CXL is useful in understanding the efficacy of CXL on improving optical, refractive, and VA.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Krachmer JH, Feder RS, Belin MW. Keratoconus and related non-inflammatory corneal thinning disorders. Surv Ophthalmol 1984; 28:293e322.  Back to cited text no. 1
    
2.
Georgiou T, Funnell CL, Cassels-Brown A, O'Conor R. Influence of ethnic origin on the incidence of keratoconus and associated atopic disease in Asians and white patients. Eye (Lond) 2004; 18:379–383.  Back to cited text no. 2
    
3.
Orucoglu F, Toker E. Comparative analysis of anterior segment parameters in normal and keratoconus eyes generated by Scheimpflug tomography. J Ophthalmol 2015; 2015:925414.  Back to cited text no. 3
    
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Romero Jimenez M, Santodomingo-Rubido J, Wolffsohn JS. Keratoconus: a review. Cont Lens Anterior Eye 2010; 33:157–166.  Back to cited text no. 4
    
5.
Jafri B, Li X, Yang H, Rabinowitz YS. Higher order wavefront aberrations and topography in early and suspected keratoconus. J Refract Surg 2007; 23:774–781.  Back to cited text no. 5
    
6.
Schwiegerling J. Cone dimensions in keratoconus using Zernike polynomials. Optom Vis Sci 1997; 74:963–969.  Back to cited text no. 6
    
7.
Hefner-Shahar H, Erdinest N. High-order aberrations in Kera-toconus. Int J Kerat Ect Cor Dis 2016; 5:128–131.  Back to cited text no. 7
    
8.
Mazzotta C, Baiocchi S, Denaro R, Tosi GM, Caporossi T. Corneal collagen cross-linking to stop corneal ectasia exacerbated by radial keratotomy. Cornea 2011; 30:225–228.  Back to cited text no. 8
    
9.
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.  Back to cited text no. 9
    
10.
Vinciguerra P, Albè E, Trazza S, Rosetta P, Vinciguerra R, Seiler T, et al . Refractive, topographic, tomographic, and aberrometric analysis of keratoconic eyes undergoing corneal cross-linking. Ophthalmology 2009; 116:369–378.  Back to cited text no. 10
    
11.
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.  Back to cited text no. 11
    
12.
El-Massry AA, Dowidar AM, Massoud TH, Tadros BGD. Evaluation of the effect of corneal collagen cross-linking for keratoconus on the ocular higher-order aberrations. Clin Ophthalmol 2017; 11:1461–1469.  Back to cited text no. 12
    
13.
Derakhshan A, Heravian Shandiz J, Ahadi M, Daneshvar R, Esmaily H. Short-term outcomes of collagen crosslinking for early keratoconus. J Ophthalmic Vis Res 2011; 6:155–159.  Back to cited text no. 13
    


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