Anterior segment optical coherence tomography analysis of regional epithelial thickness in keratoconus following intracorneal ring segment implantation

Hani M.H Elibiary; Mohamed G Aly; Raafat A Rehan; Hala M.A Najeed

doi:10.4103/djo.djo_65_22

ORIGINAL ARTICLE

Year : 2023 | Volume : 24 | Issue : 1 | Page : 10-16

Anterior segment optical coherence tomography analysis of regional epithelial thickness in keratoconus following intracorneal ring segment implantation

Hani M.H Elibiary¹, Mohamed G Aly¹, Raafat A Rehan¹, Hala M.A Najeed²
¹ Department of Ophthalmology, Faculty of Medicine, Ain Shams University, Cairo, Egypt
² Memorial Institute of Ophthalmic Research, Giza, Egypt

Date of Submission	08-Oct-2022
Date of Decision	16-Nov-2022
Date of Acceptance	20-Dec-2022
Date of Web Publication	28-Feb-2023

Correspondence Address:
Hala M.A Najeed
Department of Ophthalmology, Floor 4, Ain Shams Teaching Hospital, Abassiya, Cairo 11591
Egypt

Source of Support: None, Conflict of Interest: None

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DOI: 10.4103/djo.djo_65_22

Abstract

Background The changes in the epithelial thickness profile were found to be highly predictable and were responding to compensate for the changes in stromal curvature gradient.
Aim The aim of this study was to evaluate the epithelial thickness after intracorneal ring segment (ICRS) implantation in patients with keratoconus and to correlate it with the uncorrected visual acuity (UCVA).
Patients and methods This is a prospective nonrandomized clinical study that was conducted at the Faculty of Medicine, Ain Shams University, Cairo, Egypt. It included 24 eyes with keratoconus, which were implanted by ICRS and were scanned by CIRRUS HD-OCT 5000 preoperatively, at 1 week, 1 month, and 3 months postoperatively. The mean epithelial thickness (MET) at the cone and at the zone of ICRS implantation (5–7 mm) and UCVA were documented.
Results The MET increased significantly from a preoperative value of 42.9±6.3–50.8±7.1 µm at 3 months postoperatively (P=0.01). In addition, the mean minimum (and not the mean maximum) epithelial thickness at the 5–7-mm zone increased significantly from 35.8±4.2 µm preoperatively to 38.7±5.4 µm at 3 months postoperatively (P=0.000). There was a statistically significant negative correlation between the MET and the mean UCVA preoperatively (r=−0.389, P=0.03), at 1 week (r=−0.415, P=0.04), and at 3 months postoperatively (r=−0.479, P=0.01).
Conclusions The significant increase in the MET indicates the immediate, dynamic epithelial remodeling that continued up to 3 months after implantation. The increase in the minimum but not the maximum epithelial thickness confirms the epithelial remodeling rather than hyperplasia. The MET can be a prognostic factor for the visual outcome after ICRS as it correlated with the UCVA.

Keywords: epithelial thickness, intracorneal ring segment, keratoconus

How to cite this article:
Elibiary HM, Aly MG, Rehan RA, Najeed HM. Anterior segment optical coherence tomography analysis of regional epithelial thickness in keratoconus following intracorneal ring segment implantation. Delta J Ophthalmol 2023;24:10-6

How to cite this URL:
Elibiary HM, Aly MG, Rehan RA, Najeed HM. Anterior segment optical coherence tomography analysis of regional epithelial thickness in keratoconus following intracorneal ring segment implantation. Delta J Ophthalmol [serial online] 2023 [cited 2023 Mar 26];24:10-6. Available from: http://www.djo.eg.net/text.asp?2023/24/1/10/370770

Introduction

The long-term data of intracorneal ring segment (ICRS) procedures showed reduction of local steepening, topographic regularization, and improvement of uncorrected visual acuity (UCVA) [1],[2],[3],[4].

Anterior segment optical coherence tomography (AS-OCT) helps to diagnose keratoconus (KC) and to track the progression of the disease through epithelial thickness measurement and analysis [5],[6]. Previous studies showed that the epithelial thickness increased centrally and paracentrally after myopic LASIK [7], whereas it decreased after photorefractive keratectomy and corneal collagen crosslinking (Athens protocol) [8]. As the epithelial thickness is directly related to the corneal irregularity in a compensatory manner [9], ICRS implantation is expected to cause changes in the regional epithelial thickness.

The aim of this study was to evaluate the regional epithelial thickness in mild and moderate cases of KC preoperatively and after ICRS implantation. A more specific objective was to monitor the regional epithelial thickness changes at the cone and at the zone of ICRS implantation (5–7 mm), which has not been previously studied.

Patients and methods

In this prospective clinical study, the targeted sample size was 24 eyes with mild to moderate KC (stages I and II KC according to Amsler-Krumeich classification) [10]. Only one eye per patient was included; six eyes had stage I and 18 eyes had stage II KC. Patients with advanced KC, postoperative ectasia, central corneal thickness less than 400 μm, severe dry eye, and any preexisting corneal surgery or pathology were excluded from the study. The study protocol was adherent to the principles of the Declaration of Helsinki and was approved by Ain Shams University Medical Research Ethics Committee (MD 302018, on January 14, 2018). All patients provided a written informed consent to participate in the study and for publication of data before enrollment in the study.

All patients stopped using rigid gas permeable contact lenses at least one month before measurement. Preoperatively, corneal topography was done using an elevation-based Scheimpflug imaging device (Pentacam; Oculus, Wetzlar, Germany). UCVA and best-corrected visual acuity (BCVA) were documented. AS-OCT analysis of the corneal epithelial thickness was done before ICRS implantation by Cirrus HD-OCT 5000 (Carl Zeiss Meditec, Dublin, California, USA), which was mounted with a corneal adaptor for corneal epithelial thickness measurement. Each eye was scanned three times within each single visit by the same examiner (H.M.) to ensure map reproducibility. After proper centration and fixation, the OCT epithelial map acquisition time was less than 0.5 s. There were no reports of discomfort during the noncontact measurement. The report of epithelial and pachymetry maps was generated automatically by a computer algorithm in less than 1 min [11]. The generated epithelial map is formed of a central 2-mm zone, surrounded by three concentric zones (2–5 mm zone, 5–7 mm zone, and 7–9 mm zone). Each zone is further divided into eight sectors ([Figure 1]).

Figure 1 Epithelial thickness map (right) and pachymetry map (left) generated by CIRUSS 5000 HD-optical coherence tomography.

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Surgical technique

The same surgical technique by the same surgeon (M.G.) was applied in all patients. All included eyes had type one cone. All eyes were implanted with a single Keraring ICRS (Mediphacos, Belo Horizonte, Brazil) that has 160° arc with 250-µm thickness and fits the 5-mm optical zone. The ICRS was implanted using a purpose-designed forceps based on the surgeon-specific nomogram. The Keraring nomogram guided the ring selection taking into consideration the amount of topographic corneal astigmatism and the ectatic area distribution on the corneal surface (cone type) [12].

Surgeries were performed using a femtosecond laser (Wavelight FS200; Alcon Laboratories Inc., Fort Worth, Texas, USA) to create the tunnel. The tunnel was designed with an inner diameter of 5 mm and an outer diameter of 5.9 mm. The implant depth was calculated by subtracting 100 µm from the minimum thickness at the 5-mm optical zone, with the thinnest point along the proposed tunnel site being more than or equal to 400 µm initially [12].

Postoperatively, the mean epithelial thickness (MET) at the cone and at the zone of ICRS implantation and UCVA and BCVA were documented and correlated during the follow-up period at 1 week, 1 month, and 3 months.

Statistical analysis

The collected data were revised for completeness and consistency. Data entry was done on Microsoft Excel workbook. Quantitative data were summarized by mean and SD, whereas qualitative data were summarized by frequencies and percentages. The program used was IBM Statistical Package for the Social Sciences (SPSS) statistics for Windows, version 23 (IBM Corp., Armonk, New York, USA). Paired t test and Pearson correlation coefficient were applied to compare the difference of preoperative and postoperative MET. Linear regression was used to compare the OCT measurements. A P value less than 0.01 was considered statistically highly significant, and a P value less than 0.05 was considered statistically significant. A generalized estimating formula was used to calculate the mean of different variables.

Results

No intraoperative or postoperative complications were detected in this series of patients. Postoperatively, all eyes showed excellent incision healing and corneal tolerance to ICRS except one eye that had segment extrusion due to severe dry eye and chronic atopic keratoconjunctivitis causing corneal melt and so was excluded from the study.

The study included 24 patients, 13 (54.2%) males and 11 (45.8%) females. The mean age of the patients was 26.7±4.0 years (range=20–34 years), with11 (45.83%) eyes being right eyes, whereas 13 (54.17%) eyes were left eyes.

The mean UCVA showed a highly statistically significant improvement from 1.08±0.3 LogMAR preoperatively to 0.68±0.3 (P=0.000), 0.82±0.4 (P=0.01), and 0.72±0.4 LogMAR (P=0.001) at 1 week, 1 month, and 3 months postoperatively, respectively. The mean improvement in the UCVA was 58, 26, and 33.3% at 1 week, 1 month, and 3 months postoperatively, respectively. The improvement in the mean BCVA was not statistically significant at one week after implantation (0.56±0.2 preoperatively versus 0.43±0.32 LogMAR postoperatively, P=0.09). The mean BCVA improved significantly to 0.40±0.42 LogMAR (P=0.003) at 1 month and to 0.26±0.1 LogMAR (P=0.000) at 3 months after implantation. The mean improvement in BCVA was 23, 28.5, and 53.5% at 1 week, 1 month, and 3 months postoperatively, respectively ([Figure 2]).

Figure 2 Uncorrected and best-corrected visual acuity preoperatively and over the follow-up period following intracorneal ring segment implantation.

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The mean preoperative MET at the cone was 42.9±6.3 µm. The mean postoperative MET at the cone was 47.6±6.5, 49.1±6.5, and 50.8±7.1 µm at 1 week, 1 month, and 3 months, respectively. The increase in the MET at the cone was statistically highly significant at all follow-up periods (P=0.000). The epithelial thickness at the cone showed continuous remodeling in the form of thickening following ICRS implantation at 1 week, 1 month, and 3 months postoperatively compared with the preoperative level ([Figure 3]).

Figure 3 Epithelial thickness map preoperatively (a), at 1 week (b), at 1 month (c), and at 3 months (d) postoperatively. (a) Epithelial thickness is noted to be thinner over the cone infero-temporally (dark blue) and thicker opposite the cone (red) supero-nasally. (b) The cone got smaller and shifted up by the effect of the intracorneal ring segment (ICRS) implanted at the 5-mm zone. The epithelial thickness over it got thicker compared with the preoperative level (light blue). The epithelial thickness over the ring showed a significant increase (red). (c and d) The epithelium is noted to undergo continuous remodeling in the form of thickening over the cone (lighter shades of blue), thickening over the ring, and also opposite the ring (red).

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The mean minimum epithelial thickness in the 5–7-mm zone increased significantly from 35.84±4.2 µm preoperatively to 38.7±5.4 µm (P=0.009) at 3 months after ICRS implantation, whereas the mean maximum epithelial thickness showed no significant change from the preoperative value to all over the postoperative follow-up period ([Table 1]).

Table 1 Changes in the mean minimum and mean maximum epithelial thicknesses at the 5–7-mm zone before implantation and over the follow-up periods

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The MET of the cone had a significant negative correlation with the mean UCVA preoperatively (r=−0.389, P=0.03). There was also a significant negative correlation at one week (r=−0.415, P=0.04) and at 3 months postoperatively (r=−0.479, P=0.01) but not at 1 month postoperatively (r=−0.211, P=0.3) ([Figure 4]).

Figure 4 Correlation between the mean epithelial thickness (MET) of the cone and uncorrected visual acuity (UCVA) before intracorneal ring segment (ICRS) implantation (a) and over the follow-up period at 1 week (b) and at 3 months (c) after implantation.

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Discussion

The current study was designed to prove and document the subtle changes in corneal MET at the cone after ICRS implantation in patients with mild and moderate stages of KC and to correlate the MET with UCVA.

Since the introduction of AS-OCT, several studies have shown its value in assessing the epithelial thickness changes in different corneal pathologies and after different types of corneal surgeries [5],[6],[13],[14],[15]. The epithelial thickness changes in the form of thinning over the cone was shown to be of help in diagnosing and documenting early KC [5],[6],[9].

To minimize the surgical variables affecting the epithelial thickness changes, we chose all included patients to have type one cone, and a single ring segment that has 160° arc and 250-µm thickness was implanted. Sharma and Boxer Wachler [16] found that implanting a single ring segment provided better visual outcome when compared with those cases where two segments were implanted. Alió et al. [17] concluded that the number of segments should be based on the topographic pattern of KC and the best choice was to implant a single segment in peripheral cones and two segments in central cones. The current study conformed with both studies regarding the visual outcome after implantation and the choice of a single ring segment in peripheral type one cones.

A significant improvement in the mean UCVA was noted at 1 week, 1 month, and 3 months after ICRS implantation. The UCVA at 1 week was better than at 1 month, and this could be explained by the immediate mechanical effect exerted by the ring segment, leading to improved corneal regularity and hence reduction of corneal induced aberrations as proven before in several studies [18],[19],[20]. This mechanical effect fades away owing to adaptation, and this explains the limited improvement at one month. The UCVA improved again significantly at three months, which could be attributed to the epithelial remodeling that improved the corneal regularity.

The mechanical effect of the ICRS was maximum at the 5–7-mm zone, mainly at the cone, and this was manifested in the form of upward shifting of the cone and reduction of its size. This mechanical effect was also accompanied by a highly significant increase in the MET at the cone from 42.9±6.3 µm preoperatively to 47.6±6.5, 49.1±6.5, and 50.8±7.1 µm at 1 week, 1 month, and 3 months, respectively, after ICRS implantation. This is in accordance with previous studies which proved that the epithelial thickness correlated to the corneal irregularity in a compensatory manner in keratoconic eyes, being thinner over the cone and thicker around it (doughnut pattern) [21],[22]. This also conformed with the study of Reinstein et al. [23] which was based on the fact that the corneal epithelium masks the underlying stromal irregularities. The study investigated the efficacy of transepithelial phototherapeutic keratectomy stromal surface regularization by evaluating the changes in the epithelial thickness range, which can be defined as the difference between minimum and maximum epithelial thicknesses. Significant stromal surface regularization was achieved with the epithelial thickness range reduced on average from 41 to 29 µm. Kanellopoulos and Asimellis [8] proved that the epithelium in the keratoconic eyes treated using PRK with corneal collagen crosslinking (Athens protocol) was thinner and more homogeneously remodeled.

The mean minimum epithelial thickness in the 5–7-mm zone increased significantly from 35.84±4.2 µm preoperatively to 38.7±5.4 µm at three months after ICRS implantation, whereas the mean maximum epithelial thickness showed no significant change from the preoperative value to over the postoperative follow-up period, confirming that the process was epithelial remodeling rather than hyperplasia.

A previous study by Amanzadeh et al. [24] proved the positive correlation between the improvement of visual acuity and improvement of several topographical indices following a single ring segment implantation. In the current study, the MET at the cone had a significant negative correlation with the mean UCVA preoperatively. There was also a significant negative correlation at 1 week and 3 months postoperatively but not at 1 month postoperatively which could be explained by the fading of the mechanical regularization effect of the ring. The last two findings are unique to the present study compared with the previous studies.

One of the study limitations was the short follow-up period, probably not signifying the long-term outcome. Fewer patients is another limitation of this study. Although the choice of only type one cone was necessary to decrease the surgical variables affecting the epithelial thickness, this restricted the study from assessment of other types of cones and did not allow for comparison. Future studies are needed to assess a larger number of patients and other types of cones with different ring segment number and size.

Conclusion

To our knowledge, this is the first article studying the effect of ICRS implantation on epithelial thickness profile. ICRS implantation not only improved the UCVA but rather has a significant effect on the corneal epithelial thickness. There was an overall increase in the mean minimum but not the mean maximum epithelial thickness at the zone of implantation, meaning that the dynamic process the epithelium undergoes is a process of remodeling rather than hyperplasia. Furthermore, the MET at the cone was found to be negatively correlated with UCVA. This means that the MET can be used as a prognostic factor and could be a helpful tool in assessing the success of ICRS implantation.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

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