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 Table of Contents  
Year : 2022  |  Volume : 115  |  Issue : 2  |  Page : 78-85

Correlation between changes in corneal asphericity and progression of keratoconus in children

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

Date of Submission13-Feb-2022
Date of Acceptance26-Feb-2022
Date of Web Publication08-Jul-2022

Correspondence Address:
MD Ahmed A Tabl
Department of Ophthalmology, Asad Street, Faculty of medicine, Benha 13511
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ejos.ejos_11_22

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Clinical relevance Early detection of keratoconus (KC) progression and timing for retreatment.
Background Q value (coefficient of corneal asphericity) reflects the shape of the cornea, its refractive power, and spherical aberration. In this study, we aimed to analyze the correlation between changes in Q value and progression of KC in children.
Patients and methods In this retrospective cross-sectional study, clinical data of 18 eyes of nine children that were diagnosed as bilateral progressive KC (four boys, five girls: mean age of 11.3±1.6 years) were extracted from a Scheimpflug camera (Pentacam) for analysis before (baseline) and annually after bilateral transepithelial corneal collagen cross-linking (TE-CXL) up to 5 years of follow-up.
Results At all follow-up visits up to 5 years, Kmax improved significantly (mean change at 5 years was 1.6 D) (P<0.001); uncorrected visual acuity and best-corrected visual acuity showed significant changes at all follow-up visits (P<0.001). In seven (38.8%) eyes, KC had progressed by more than 1.0 D by the last follow-up visit, despite corneal cross-linking. In the last visit, there was a significant negative correlation between mean Q value and Kmax in both 6 and 8 mm anterior corneal zones (Pearson correlation coefficient, r=−0.847, P<0.001, r=−0.605, P<0.001, respectively).
Conclusion There is significant negative correlations between changes in corneal asphericity and progression of KC in children, which could be considered with other parameters in early detection of disease progression and timing for retreatment after transepithelial corneal collagen cross-linking.

Keywords: accelerated, corneal collagen cross-linking, keratoconus, transepithelial

How to cite this article:
Tabl AA, Elsayed MA, Tabl MA. Correlation between changes in corneal asphericity and progression of keratoconus in children. J Egypt Ophthalmol Soc 2022;115:78-85

How to cite this URL:
Tabl AA, Elsayed MA, Tabl MA. Correlation between changes in corneal asphericity and progression of keratoconus in children. J Egypt Ophthalmol Soc [serial online] 2022 [cited 2022 Sep 28];115:78-85. Available from: http://www.jeos.eg.net/text.asp?2022/115/2/78/350246

  Introduction Top

Keratoconus (KC) is a progressive corneal disease characterized by asymmetric corneal thinning and structural changes in corneal collagen, which leads to a decrease in visual acuity due to myopic shift, irregular astigmatism, or corneal scarring. KC is a common cause for corneal transplantation in young patients [1]. Early detection of the disease in children aids in halting the progression and improve their quality of life [2].

The Amsler–Krumeich grading classification is still widely used for the assessment of KC and its progression, based on changes in anterior corneal surface, minimal corneal thickness (MCT), and manifest refraction [3],[4]. Recently, Belin ABCD grading system has been introduced. This was incorporated into a Scheimpflug tomography-based device (Pentacam HR), anterior and posterior corneal curvature, MCT, and best-corrected visual acuity (BCVA) are measured from a 3.0 mm zone that is centered on the thinnest location [5].

KC progression is defined as increasing by 1.0 D or more in the maximum keratometry (Kmax) [6]; progressive deterioration in MCT is also associated with KC progression [6],[7]. Other methods have been investigated to confirm KC progression such as changes in manifest refraction, unaided visual acuity, BCVA, posterior keratometric data, and higher order aberrations, which are altered in KC and can aid in confirming disease progression [7],[8]. Q value (a coefficient of corneal asphericity) reflects the shape of the cornea, its refractive power, and spherical aberration [9]. The mean Q value in normal cornea is −0.26±0.18; the severity of KC and the Q value are inversely related [10]. Mean Q value in KC at the 8 mm zone is −0.84 and −1.10 for anterior and posterior corneal surfaces, respectively [11]. Until now, there is no precise criteria of KC progression especially in cases that had undergone previous transepithelial corneal collagen cross-linking (TE-CXL) to halt the progression of disease [7],[8]. In the present study, we aimed to analyze the correlation between the changes in Q value and progression of the KC in children who had undergone bilateral TE-CXL.

  Patients and methods Top

This retrospective observational study was performed at the Ophthalmology Department, Benha University, Egypt using the medical records of nine children diagnosed as bilateral progressive KC that was confirmed by Pentacam (OCULUS Optikgeräte GmbH, Wetzlar, Germany) according to Amsler criteria [3]. Data was checked by a cornea consultant (M.A.S.); patients had undergone bilateral TE-CXL in the period from January 2016 to August 2016 at Ebsar Eye Center, Benha, Egypt by the same surgeon (A.A.T.), and they had completed their annual visits till 5 years of follow-up. This study was approved by the Institutional Review Board, Faculty of Medicine, Benha University and adhered to the principles of the Declaration of Helsinki and was registered on ClinicalTrials.gov (identifier, NCT05114928). A written informed consent was obtained from the parents or children legal representatives before the procedure.

Inclusion criteria

Children who were diagnosed as bilateral progressive KC (stages I–III, according to Amsler Classification, Kmax change more than 1 D between two scannings with at least 4 months apart) [3], and whose ages were less than 16 years at the time of TE-CXL, no history of refractive surgery or contact lenses wear, cooperative to get a good scanning by Pentacam that was deemed by ‘OK’ in the device software, and their records had complete ophthalmic examination and annual Pentacam scanning. Topographic parameters were Kmax 47–60 D and MCT more than 400 µm. Exclusion criteria: eyes with central corneal scarring, amblyopic eyes, and other corneal pathologies that may alter Pentacam scanning.

Surgical procedure

Local anesthetic eye drops containing benoxinate hydrochloride 0.4% (Benox; Epico, Egypt) were administered in both eyes. Following the manufacturer’s nomogram, riboflavin 0.25%, hydroxypropyl methylcellulose and benzalkonium chloride (ParaCel; Avedro Inc.) were applied to the cornea every 90 s for 4.50 min. Dextran-free isotonic riboflavin 0.22% (VibeX Xtra; Avedro Inc.) was then applied every 90 s for 6 min, followed by ultraviolet A irradiation 9 mW/cm2 at 55 mm from the cornea for 10 min, with a total energy of 5.4 J/cm2 using the (CCL Vario; Peschke Trade GmbH, Huenenberg, Switzerland). Then, the cornea was washed out with a balanced salt solution. Bandage contact lens was applied and removed after 2 days. Moxifloxacin (Vigamox 0.5%; Alcon) and fluorometholone 0.1% (FML 0.1%, Allergan) eye drops were prescribed four times/day for 1 week. Patients were scheduled for follow-up 48 h and 1 week after the procedure.

In this study, Pentacam was done before TE-CXL (baseline scanning) and annually after TE-CXL till 5 years of follow-up. The following data was extracted from each patient visit: anterior and posterior corneal elevation on the thinnest location, Kmax, MCT, anterior, and posterior mean Q values on 6 and 8 mm zones by the best-fit sphere method. Manifest refraction was done for each visit using an autorefractometer (Topcon RM8900 Co. Ltd, Japan).

Retreatment according to disease progression

Eyes that were found to have KC reprogression during annual visits were retreated to avoid deterioration of the children’s visual outcome. In such cases, we planned to statistically analyze the data of these eyes till last visit before retreatment, which was done using epithelium-off CXL (standard Dresden protocol) [12].

Data management

The clinical data were recorded on a report form. These data were tabulated and analyzed using the computer program SPSS (Statistical package for social science) version 26 (IBM, Armonk, New York, USA) to obtain.

Descriptive data

Descriptive statistics were calculated for the data in the form of mean and SD for quantitative data.

Analytical statistics

In the statistical comparison between the different parameters, the significance of difference was tested using one of the following tests:
  1. Paired t test: used to compare the mean of variables in different time periods of quantitative data.
  2. Friedman test: used to compare the mean of more than two follow-up periods at the same group of quantitative data.
  3. Correlation coefficient: to find relationships between variables.

A P value less than 0.05 was considered statistically significant while more than 0.05 statistically insignificant. P value less than 0.01 was considered highly significant in all analyses.

  Results Top

In this retrospective observational study 18 eyes of nine children with progressive KC (five girls and four boys with a mean age of 11.3±1.6 years old) had undergone TE-CXL and were followed-up annually for 5 years using Pentacam. Data were analyzed for the possible correlation between Kmax and corneal asphericity at different corneal zones: mean Q value at an anterior corneal zone of 6 mm ‘MQA.6’, mean Q value at an anterior corneal zone of 8 mm ‘MQA.8,’ and mean Q value at a posterior corneal zone of 6 mm ‘MQP.6’ ([Table 1]).
Table 1 Comparison of the demographic and Pentacam parameters for the studied group of patients through their scheduled visits

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Significant correlations were observed between Kmax and MQA.6 at last two visits (r=−0.755 and −0.847, respectively; P<0.001 for both, Pearson correlation coefficient) ([Figure 1], [Table 2]). There was also a significant correlation between Kmax and MQA.8 at last visit (r=−0.605; P=0.008) ([Figure 2]). There were no significant correlations between Kmax and MQP.6 at all follow-up visits ([Figure 3]).
Figure 1 Correlations between Kmax and MQA.6 (mean corneal asphericity at 6 mm anterior corneal zone).

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Table 2 Correlations between Kmax and MQA.6, MQA.8, and MQP.6

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Figure 2 Correlations between Kmax and MQA.8 (mean corneal asphericity at 8 mm anterior corneal zone).

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Figure 3 Correlations between Kmax and MQP.6 (mean corneal asphericity at 6 mm posterior corneal zone).

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Mean baseline BCVA (LogMAR units) was 0.35 and at last visit the mean BCVA was 0.41 ([Table 1]). Mean baseline MCT was 463.33±20.95 μm and was reduced to 441.22±22.90 μm. Mean baseline Kmax was 56.27±2.88 D and at last visit mean Kmax was 54.66±3.89 D. Seven eyes showed an increase of Kmax of more than 1 D at the last visit compared with the previous visit and retreatment was done for these eyes. No reported complications were found after TE-CXL in all eyes in our study.

  Discussion Top

In this retrospective study, we analyzed the correlation between the changes in anterior, posterior mean Q value and the degree of KC progression in 18 eyes of nine children who had undergone previous TE-CXL. We aimed to investigate these changes in different corneal zones to find if they could be used as a predictive factor for early detection of KC reprogression after TE-CXL, in addition to the previously widely used criteria as changes in Kmax and MCT [6],[7].

TE-CXL protocols were reported to be effective as the standard Dresden protocol in pediatric KC, taking advantage of shortening the duration of treatment based on the Bunsen and Roscoe law of reciprocity [13],[14],[15].

Previous studies have reported a reduction in the efficiency of high-energy TE-CXL (as power=18 and 45 mW/cm2) due to limited intra-stromal oxygen diffusion capacity and increased oxygen consumption associated with higher irradiances [14],[16],[17]. We used an accelerated protocol of 9 mW/cm2 for 10 min, which had been reported previously to be safe and effective in progressive KC [18],[19],[20],[21]. Perez-Straziota et al. [20] concluded that studies conducted on TE-CXL in pediatric KC showed comparable results with the standard Dresden protocol, but a longer period of follow-up is still needed to assess incidence of progression. Kirgiz et al. [21] concluded that the group treated with epi-off CXL (n=29 eyes, power=9 mW/cm2) showed better topographic improvements than the group that was treated with higher energy by the same technique (n=37 eyes, power=18 mW/cm2).

Mazzotta et al. [22] reported that KC progression had occurred among 13 (8.33%) eyes out of 156 eyes after epi-off CXL using a power of 9 mW/cm2, during 5 years of follow-up. Our results showed a higher incidence of recurrence (38.8%) over 5 years of follow-up and the explanation is that epi-off CXL may have a better effect on corneal stiffness in the long run; also the sample size in this study is smaller.

We believe that standard epi-off CXL has longer stability than both TE-CXL and accelerated-CXL, according to previous reports [22] but TE-CXL was performed in this study after discussing all sequels with parents and the possibility of retreatment trying to avoid any potential hazards as postoperative corneal haze or delayed epithelial healing.

Clinically, it is still debatable which topographic parameters we should rely on to confirm the disease progression especially after TE-CXL [23].

Gustafsson et al. [24] concluded that depending on the increase by 1 D of Kmax for all KC stages could be misleading, as mild cases could be misinterpreted as nonprogressive, while advanced cases could be misdiagnosed as progressive disease. Gustafsson et al. [25] reported that KC progression can be detected by the change in magnitude between the means of four replicates in 25 eyes with low-grade KC as follows: 0.44 D in the flattest central keratometry, 0.72 D in the steepest central keratometry, 0.84 D in Kmax, and 8.11 µm in MCT or 0.21 mm change in the least radius of curvature (Rmin).

Mofty et al. [26] evaluated the changes in anterior corneal asphericity over 12 months in 18 KC eyes that were treated by CXL. They concluded that there was a positive shift in anterior Q value at 6 and 8 mm zones 1 year after CXL, but there was a negative correlation between these changes and BCVA and Kmax after 12 months of follow-up. These results are in accordance to ours, but with longer follow-up in our study. We found a negative shift in the anterior Q value at 6 mm at the last visit and this is due to reprogression that had occurred in the fifth year in 38.8% of eyes.

Koller et al. [27] examined the changes in Q value (anterior and posterior) at a 8 mm zone in 21 patients (range, 18–51 years old) with progressive KC treated by Epi-off CXL in one eye and their fellow untreated eyes were served as control . After 12 months they concluded that there were no significant changes in Q values in cross-linked eyes; however, among 21 untreated eyes, eight eyes showed KC progression with significant shift toward a minus value in mean anterior Q value. Also, there was significant increase in Rmin (flattening) among the treated eyes and significant decrease (steepening) in progressive eyes. Their results among the treated eyes are in accordance with our study except that we studied a younger age group and our longer follow-up showed a significant change in anterior Q value at 6 mm due to reprogression of the disease.We did not compare the changes in Q values with normal participants as there will be overestimation of KC progression, when comparing with a healthy cohort over a long period of follow-up.

One of the limitations of our study is the small sample size. So we did not classify progressive eyes to subgroups according to the severity of the KC or cone location. The new Belin ABCD grading system was not available in our area at the time of data extraction. Savini et al. [28] concluded that the repeatability of the anterior and posterior Q value measurements was good when measured using Pentacam, with an intra-class correlation coefficient of more than 0.9 in the KC group. We did not perform test–retest reliability because of a long period of follow-up and it was not the scope of this research.

The mean Q value of the anterior cornea at the 6 mm zone is a good indicator for KC progression that could be correlated with other parameters as changes in Kmax and MCT to confirm disease progression after previous TE-CXL.

Further studies are still needed to investigate interday repeatability limits in measuring Q values in progressive KC, and its relation to the stage of KC.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

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  [Figure 1], [Figure 2], [Figure 3]

  [Table 1], [Table 2]


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