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 Table of Contents  
ORIGINAL ARTICLE
Year : 2022  |  Volume : 20  |  Issue : 3  |  Page : 259-265

Effect of corneal collagen cross-linking on higher-order aberrations in patients with early keratoconus


Department of Ophthalmology, Faculty of Medicine, Al-Azhar University (Assiut Branch), Assiut, Egypt

Date of Submission22-Aug-2021
Date of Decision09-Oct-2021
Date of Acceptance11-Oct-2021
Date of Web Publication11-Oct-2022

Correspondence Address:
MBBCh Shimaa B Sayed
Department of Ophthalmology, Faculty of Medicine, Al-Azhar University, Assiut, 71511
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/azmj.azmj_96_21

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  Abstract 


Background and aim Collagen cross-linking (CXL) is the available treatment to arrest the progression of keratoconus (KC). It consists of photopolymerization of collagen induced by combined action of a photosensitizing substance, and ultraviolet-A light.
The aim of the study is to assess higher-order aberrations (HOAs) of cornea in patients with early KC before and after cross-linking using the Bausch & Lomb Zywave II aberrometer.
Patients and methods In total, 30 patients (nine males and 21 females), aged 19–35-years old with mild KC. HOAs examination was done using Zywave device before and after corneal CXL and followed up 1, 3, and 6 months postoperative.
Results Preoperative and postoperative 1-month Root Mean Square (RMS) of the total HOA differences was statistically insignificant with P value of 0.102, however, preoperative and postoperative 3 and 6 months showed higher significance with P value of 0.007 and P value less than 0.001, respectively. Preoperative and postoperative 1-month RMS of total coma-order aberration differences was statistically insignificant (P=0.211), however preoperative and postoperative 3 and 6 months showed higher significance with P value of 0.024 and value less than 0.001, respectively. Preoperative and postoperative 1- and 3-month secondary astigmatism-aberration differences were statistically insignificant (P=0.070 and 0.216, respectively), however preoperative and postoperative 6 months showed higher significance with P value less than 0.001.
Conclusion There is reduction in the parameters of HOAs after CXL in patients with KC, especially total HOA, coma, and secondary astigmatism aberrations.

Keywords: keratoconus, optical aberrations, Zywave


How to cite this article:
Yousef HS, Salih MA, Sayed SB. Effect of corneal collagen cross-linking on higher-order aberrations in patients with early keratoconus. Al-Azhar Assiut Med J 2022;20:259-65

How to cite this URL:
Yousef HS, Salih MA, Sayed SB. Effect of corneal collagen cross-linking on higher-order aberrations in patients with early keratoconus. Al-Azhar Assiut Med J [serial online] 2022 [cited 2023 Mar 22];20:259-65. Available from: http://www.azmj.eg.net/text.asp?2022/20/3/259/358041




  Introduction Top


Keratoconus (KC) is one of the commonest corneal ectatic diseases. It is a bilateral disease but asymmetric, with characteristic progressive thinning and corneal steeping [1].

In Egypt, the prevalence of KC was 170/100 000 at age 21–36. The environmental factor could be increase the risk of the KC in genetically predisposed individuals. Environmental factors, such as ultraviolet (UV) exposure, rubbing of the eye, and atopy, although the contribution of all the factors is currently unknown [2],[3].

Several studies have found that keratoconic eyes have much higher ocular and corneal aberrations than normal eyes [4].

In a perfect eye, light hits the retina at a succinct single point, but even in most normal eyes, the light hits the retina in different points, which leads to a defect in the visual image, that was called wave-front aberration. The shape of the wavefront often differs if the waves emanating from a light source hit an irregular optical surface, such as a keratoconic cornea [5].

The Bausch & Lomb Zywave II aberrometer is an important device in detecting high-order aberrations (HOAs) for grading the stage of KC [6]. After collagen cross-linking (CXL), a change in HOAs is helpful in assessing the efficacy of CXL in increasing refraction and visual acuity (VA). HOA indices in KC patients treated with CXL were significantly reduced [7].

CXL with UV-A light and vitamin B2 (riboflavin) slows the progression of KC. CXL utilizes vitamin B2 as a photosensitizer, which, when exposed to UV-A, induces chemical reactions in the corneal stroma and results in the formation of covalent bonds between the collagen molecules that increases rigidity of the cornea [8].

The aim of the study was to assess the effect of corneal CXL on HOAs of the cornea in patients with early KC using the Bausch & Lomb Zywave II aberrometer.


  Patients and methods Top


A prospective cohort study was carried out in a private specialist eye center (Al Nahar Eye Center). A total of 50 eyes of 30 patients (nine males and 21 females), with a mean age of 24.33±4.88 years (range, 19–35 years). The procedures took place between September 2019 and January 2021.

Inclusion criteria

Patients with mild KC [corneal thickness ≥400 μ, K-reading ≥47.8 D, and <53.00 D, asymmetric Bowtie pattern, the inferior–superior (I–S) value between 1.4 and 1.9 D, and myopia and astigmatism ≥5.00 D and <8.00 D].

Exclusion criteria

Patients with moderate, severe KC, history of corneal surgery, chemical burn, systemic collagen disease, pregnancy and lactation, corneal scarring, and history of herpetic keratitis.

All patients were subjected to the following: uncorrected visual acuity (UCVA), best-corrected visual acuity (BCVA), slit lamp, fundus examination, and corneal topography: preoperative (baseline) corneal topography using the Sirius Pentcam, HOA evaluation was done using Zywave 3 diagnostic device.

Treatment

Collagen cross-linking.

This was performed under topical anesthesia, Benoxinate HCL drops 0.4% instilled twice 2 min apart before the treatment under standard sterile conditions. Povidone iodine 10% used for skin disinfection.

Under an operating microscope, with a lid speculum inserted and an epithelium-off technique, the central 7–8 mm of the corneal epithelium was debrided with a hockey knife or phototherapeutic keratectomy. To ensure optimal vitamin-B2 absorption in the stroma, riboflavin (0.1% solution) instillation slit-lamp biomicroscopy revealed a yellow coloration in the anterior chamber after 10 mg of riboflavin-5-phosphate in 10 ml of Dextran-T-500 20% solution that was applied every 5 min for 30 min, until the stroma was completely penetrated and a yellow coloration was noticed in the anterior chamber. Central UV-A (370 nm) at 3 mW/cm2 was applied to 7–8 mm of the cornea for 30 min. The ocular surface was irrigated with a balanced salt solution, and a bandage soft contact lens was applied at the end of the treatment to keep the corneal epithelialization process going.

The following are the postoperative treatments: prednisolone acetate 1% eye drops (topical steroid) from the third day should follow the antibiotic and tear substitutes. The antibiotic (Moxifloxacin 0.5% eye drops) four times a day for 1 week, after that, the antibiotic drops were discontinued. For the next week, the steroid was decreased to three times per day, then two times per day for the next 2 weeks. For 4–6 weeks, tear substitutes (preservative-free artificial tears) were given four times daily.

Follow-up

On the first day, all patients were checked on the third day, first week, 1 month, 3 months, and 6 months postoperative. In each visit, the following was assessed: VA, UCVA, BCVA, and MR. Zywave II aberrometer was performed at the first-month, 3-month, and 6-months’ follow-up visits.

Ethical consent

An approval of the study was obtained from Al-Azhar University academic and ethical committee. Every patient signed an informed written consent for acceptance of the operation.

Statistical analysis

The mean and SD values were calculated for each group in each test. Data were explored for normality using Kolmogorov–Smirnov and Shapiro–Wilk tests and showed nonparametric (not normal) distribution.

Categorical variables were described by number and percent, where continuous variables were described by mean and SD (mean, SD, and median).

Wilcoxon t test was used to compare between two different periods of the variable values.

The significance level was set at P value less than 0.05. Statistical analysis was performed with IBM SPSS Statistics, Version 26 for Windows.


  Results Top


In total, 50 eyes examination in 30 patients revealed the following.

Demographic results

The study population consisted of 21 females and nine males. The mean age of the patients was 24.33±4.88 years ranging from 19 to 35 years.

Results of uncorrected visual acuity

The mean preoperative UCVA was 0.157±0.319. Postoperative UCVA at 1 month was 0.072±0.0322, while in 3 months, it was 0.0730±0.0323 and in 6 months was 0.148±0.0735. Preoperative and postoperative 1- and 3-month UCVA differences were not statistically significant, P value of 0.157 and 0.083, respectively. However, preoperative and postoperative 6 months showed higher significance with P value less than 0.001 ([Table 1], [Figure 1]).
Table 1 Pre-collagen cross-linking and 1-, 3-, and 6-month post-collagen cross-linking uncorrected visual acuity and best-corrected visual acuity comparison

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Figure 1 Comparison between the pre-CXl and one, three and six months post-CXl according to UCVA.

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Results of best-corrected visual acuity

The mean preoperative BCVA was 03160±0.1243. Postoperative BCVA at 1 month was 0.3234±0.1388, while in 3 months was 0.3310±0.1351 and in 6 months was 0.3900±0.1638. Preoperative and postoperative 1- and 3-month BCVA differences were not statistically significant, P value 0.447 and 0.151, respectively, however, preoperative and postoperative 6 months show higher significance with P value less than 0.001 ([Table 1], [Figure 2]).
Figure 2 Comparison between the pre-CXl and one, three and six months post-CXl according to BCVA.

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RMS of total high-order aberrations

The mean preoperative HOAs were 3.5728±1.5228. Postoperative HOA at 1 month was 3.5688±1.5211, while in 3 months was 3.5078±1.4799 and in 6 months was 2.684±1.4465. Preoperative and postoperative 1-month RMS of total HOA differences was not statistically significant, P value of 0.102 and, however, preoperative and postoperative 3 and 6 months show higher significance with P value 0.007 and less than 0.001, respectively ([Figure 3]).
Figure 3 Comparison between the pre-CXl and one, three and six months post-CXl according to RMS of total HOAs.

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The mean preoperative RMS of total coma-order aberrations was −1.3682±0.8102. Postoperative coma-order aberrations at 1 month were −1.3560±0.8354, while in 3 months was −1.32±0.9 and in 6 months was −0.8960±0.8644. Preoperative and postoperative 1-month RMS of total coma-order aberrations difference was not statistically significant, P value of 0.211 and, however preoperative and postoperative 3 and 6 months show higher significance with P value 0.024 and less than 0.001, respectively ([Table 2]).
Table 2 Comparison between the pre-collagen cross-linking and 1-, 3-, and 6-month post--collagen cross-linking according to RMS of total high-order aberrations and RMS of total coma-order aberrations

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Trefoil aberrations

The mean preoperative trefoil aberrations were 0.5556±0.3279. Postoperative trefoil aberrations at 1 month were 0.5552±0.3275, while in 3 months was 0.55507±0.3276 and in 6 months was 0.5546±0.3276. Preoperative and postoperative 1-, 3-, and 6-month MR spherical differences were not statistically significant ([Figure 4]).
Figure 4 Comparison between the pre-CXl and one, three and six months post-CXl according to trefoil aberrations.

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Astigmatism aberrations

The mean preoperative secondary astigmatism aberrations were −0.2794±0.2543. Postoperative secondary astigmatism aberrations at 1 month were −0.2742±0.2481, while in 3 months was −0.2752±0.2532 and in 6 months was −0.1656±0.2111. Preoperative and postoperative 1- and 3-month secondary astigmatism aberration differences were not statistically significant, P value of 0.07 and 0.216, respectively, however, preoperative and postoperative 6 months show higher significance with P value less than 0.001 ([Table 3], [Figure 5]).
Table 3 Comparison between the pre-collagen cross-linking and 1-, 3-, and 6-month post-collagen cross-linking according to trefoil aberrations and secondary astigmatism aberrations

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Figure 5 Comparison between the pre-CXl and one, three and six months post-CXl according to secondary astigmatism aberrations.

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Thinnest corneal thickness

The mean preoperative thinnest corneal thickness was 449.88±30.706. Postoperative thinnest corneal thickness at 6 months was 424.4±25.864. Preoperative and postoperative thinnest corneal thickness differences were statistically significant (P<0.001) ([Table 4], [Figure 6]).
Table 4 Pre-collagen cross-linking and 6-month post-collagen cross-linking comparison of K-max and thinnest corneal thickness

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Figure 6 Comparison between corneal thickness at the thinnest point pre- and six months post-CXl.

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  Discussion Top


As regarding the UCVA, the mean preoperative UCVA was 0.0700±0.0319. Mean postoperative UCVA at 1 month was 0.0720±0.0322, while at 3 months, it was 0.0730±0.0323and at 6 months it was 0.1480±0.0735.

Preoperative and postoperative 1- and 3-month UCVA differences were statistically insignificant, P value of 0.157and 0.083, respectively, however, preoperative and postoperative 6 months show higher significance with P value less than 0.001.

Amer et al. [9] study was conducted on 18 eyes of 13 KC patients, seven males and six females who underwent CXL. The preoperative UCVA on the day of treatment was compared with the postoperative UCVA at 12-month examination. This showed that UCVA improved at least one line in 88.9% (16 out of 18 patients) of eyes and decreased by only one line in 11.1% (two out of 18 patients). The study concluded that CXL is a favorite treatment tool and first line of treatment for progressive KC.

Despite the difference in the time periods in this study and ours, it is obvious that they are in agreement regarding the improvement in UCVA preoperative compared with postoperative. As a matter of fact, as our study only followed patients for 6 months after the procedure, it might be wise to assume more improvement if given more time for follow-up, and probably yield the same results if the UCVA of earlier than 6-month follow-ups were ignored.

Razmjoo et al. [10] conducted a study on 66 patients with progression of KC during 1 year, the mean UCVA was not significantly improved 12 months after surgery (0.29±0.36 log MAR to 0.29±0.32 log MAR, a P=0.736).

Tawakol et al. [11] performed their study on 30 eyes of 18 patients,12 females and 18 males, who underwent corneal CXL using riboflavin and UV-A light, there was a highly statistically significant improvement in the mean UCVA postoperatively compared with that of preoperative with a P value of 0.001. The mean preoperative UCVA was 0.17±0.12, while the mean postoperative UCVA at the first visit (1 month) was 0.25±0.16, and the mean postoperative UCVA at the last visit (4 month) was 0.27±0.14.

As regarding BCVA, the mean preoperative BCVA was 0.3160±0.1 243. Postoperative BCVA at 1 month was 0.3234±0.1 388, while in 3 months was 0.3310±0.1 351 and in 6 months was 0.3900±0.1638. Preoperative and postoperative 1- and 3-month BCVA differences were not statistically significant (P=0.447 and 0.151), respectively, however, preoperative and postoperative 6 months show higher significance with P value less than 0.001.

Amer et al. [9], as mentioned before, it was also reported that ten patients out of the 18 patients included in the study had documented reduction in BCVA by one line or more. The same results were obtained from a study by Mirzaei et al. [12], conducted on 40 eyes diagnosed as progressive KC, where the BCVA did not change significantly. Both studies were in agreement with our study too.

The mean preoperative RMS of total HOAs: HOAs were 3.5728±1.5228, postoperative HOAs at 1 month were 3.5688±1.5228, while in 3 months, were 3.5078±1.4799 and in 6 months were 2.684±1.4465. Preoperative and postoperative 1-month RMS of total HOA differences was not statistically significant, P value of 0.102 and, however preoperative and postoperative 3 and 6 months show higher significance with P value 0.007 and less than 0.001, respectively.

The mean RMS of total coma-order aberrations before surgery was −1.3682±0.8102. Postoperative coma-order aberrations were −1.3560±0.8354 at 1 month, −1.32±0.9 at 3 months, and −0.8960±0.8644 at 6 months. Preoperative and postoperative 1-month RMS of total coma-order aberration differences was not statistically significant (P=0.211), but preoperative and postoperative 3 and 6 months showed higher significance (P=0.024 and 0.001, respectively).

A study by El-Massry et al. [13], which was carried out on 30 eyes of 16 patients suffering from progressive KC, showed that after 6 months, total HOAs and total coma had statistically significantly decreased by 25 and 18%, respectively. Spherical aberration improved by 8.71% (P=0.001), while trefoil and high-order astigmatism remained unchanged (P=0.405 and 0.329, respectively). This was in agreement with our results in an international prospective manner.

Another study by Mo’mena et al. [14], agreed with our results where RMS HOA recorded a higher mean value preoperatively, with a high statistically significant difference (P=0.00), and all elements of HOAs showed lower postoperative values, except for trefoil 30°. The difference was statistically significant in coma 0°, coma 90°, spherical aberrations, and fifth-order comm 90° (P=0.026, 0.003, 0.005, and 0.001, respectively).

The mean preoperative K-max was 48.7628±0.7944. Postoperative K-max at 6 months was 48.7400±0.8213. Preoperative and postoperative K-max differences were statistically not significant (P=0.979).

In contrast to our results, the study mentioned before by Amer et al. [9], reported that the average K value decreased by at least 1.00 D in 44.4% (eight out of 18 patients) eyes and remained stable (within ±1.00 D) in 55.6% (10 out of 18 patients) of eyes between baseline and 12-month postoperative values. The average K-max preoperatively was 47.44±2.65 and postoperatively was 46.02±2.739 with a significant P value of 0.00.

The same was observed in the study by Iqbal et al. [15], where the mean preoperative K-max reduced from preoperative 51.95±1.90 D (mean±SD) to 51.15±2.03, 50.64±1.86, 50.27±1.92, and 50.19±1.96 D at postoperative 12, 24, 36, and 60 follow-up months (P<0.001).

The mean preoperative thinnest corneal thickness was 449.88±30.706. Postoperative thinnest corneal thickness at 6 months was 424.44±25.864. Preoperative and postoperative thinnest corneal thickness differences were statistically significant (P<0.001).

In a study by Lago et al. [16], designed to evaluate changes in corneal sensitivity following CXL in patients with progressive earlier-stage KC, 38 eyes of 19 patients; 11 women and eight men, were included in a prospective, nonrandomized clinical study. The mean thickness as assessed by central corneal pachymetry decreased from 478±24.8 to 454±29.06 μm 3 months after surgery, which was statistically significant with a P value of 0.00.

Despite the difference in the procedure used between the two studies, where in our study, the thinnest corneal thickness was assessed, while in the study by Lago et al. [16] and the different follow-up period given, 6 months in our study and 3 months in Lago’s study, the central corneal thickness was assessed, the decrease in the corneal thickness was statistically significant in both studies.

Regarding the difference in the time factor, our study actually has the upper hand in proving the point as it spans a longer postoperative time period. The same results were obtained from the study mentioned before by Razmjoo et al. [10], where the thinnest corneal thickness was measured preoperative and 12-months postoperative. The mean preoperative thinnest corneal thickness was 459.17 μm and the mean postoperative thinnest corneal thickness decreased to 446.05 μm with a statistically significant P value of 0.013.

The limitations of this study, short term of follow-up.

In patients with KC, CXL results in a considerable reduction in HOA indices, especially total HOA, coma, and secondary astigmatism aberrations.

We recommend to assessing the HOA in progression of KC by Zywave diagnostic device.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

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Sharif R, Bak-Nielsen S, Hjortdal J, Karamichos D. Pathogenesis of keratoconus: the intriguing therapeutic potential of prolactin-inducible protein. Prog Retin Eye Res 2018; 67:150–167.  Back to cited text no. 1
    
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Davidson AE, Hayes S, Hardcastle AJ, Tuft SJ. The pathogenesis of keratoconus. Eye (Lond) 2014; 28:189–195.  Back to cited text no. 2
    
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Omer K. Epidemiology of keratoconus worldwide. Open Ophthalmol J 2018; 12:71–79.  Back to cited text no. 3
    
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Naderan M, Jahanrad A, Farjadnia M., Ocular, corneal, and internal aberrations in eyes with keratoconus, forme fruste keratoconus, and healthy eyes. Int Ophthalmol 2018; 38:1565–1573.  Back to cited text no. 4
    
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Naderan M, Jahanrad A. Higher-order aberration 4 years after corneal collagen cross-linking. Indian J Ophthalmol 2017; 65:808–813.  Back to cited text no. 6
[PUBMED]  [Full text]  
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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. 7
    
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Vohra V, Tuteja S, Chawla H. Collagen cross linking for keratoconus. StatPearls [Internet] 2020; ■:■.  Back to cited text no. 8
    
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Amer AA, Abdellatif MA, Radwan GA. Role of corneal collagen cross-linkage in the treatment of keratoconus. AAMJ 2014; 12:17–21.  Back to cited text no. 9
    
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Razmjoo H, Nasrollahi AP, Salam H, Karbasi N, Najarzadegan MR. Topographic corneal changes after collagen cross-linking in patients with corneal keratoconus. J Res Med Sci 2013; 18:882–888.  Back to cited text no. 10
    
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Tawakol ME, Tag El-Din AE, Hassan AG. Corneal hysteresis before and after corneal collagen cross linking for keratoconus. Egypt J Hosp Med 2019; 77:5759–5765.  Back to cited text no. 11
    
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Mirzaei M, Mortazavi SZ, Taheri N, LotfiSadigh A, Najafi A. Effects of collagen cross-linking on the corneal optical and topographic characteristics in progressive keratoconus. Adv Ophthalmol Vis Syst 2015; 2:00043.  Back to cited text no. 12
    
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El-Massry AA, Dowidar AM, Massoud TH, Tadros BG. Evaluation of the effect of corneal collagen cross-linking for keratoconus on the ocular higher-order aberrations. Clin Ophthalmol 2017; 11:1461–1467.  Back to cited text no. 13
    
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Mo’mena AA, Moamen S, Ahmed A, Tamer EM, Rafeek EG. Assessment of corneal higher order aberrations before and after corneal collagen cross-linking in patients with keratoconus. Egypt J Hosp Med 2018; 72:4100–4103.  Back to cited text no. 14
    
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Iqbal M, Elmassry A, Badawi AE, Gharieb HM, Said OM. Visual and refractive long-term outcomes following standard cross-linking in progressive keratoconus management. Clin Ophthalmol 2019; 13:2477–2479.  Back to cited text no. 15
    
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Lago AD, Nassaralla BR, Stival LR, Nassaralla Junior JJ. Changes in corneal sensitivity following cross-linking for progressive early-stage keratoconus. Arq Bras Oftalmol 2014; 77:84–87.  Back to cited text no. 16
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4]



 

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