Aberrometric Outcomes of Intrastromal Corneal Ring Segment (KeraRing 355) Implantation Using PocketMaker Microkeratome in Patients with Keratoconus

Objective: To evaluate aberrometric changes in corneas with keratoconus implanted with intrastromal corneal ring segment (Keraring 355) during a 3-months follow-up. Design: Prospective, consecutive case series Methods: In this interventional study, 22 eyes of 21 keratoconic patients with mean age of 29 ± 6 years who underwent KeraRing 355 intrastromal corneal ring insertion using a Pocket Maker Microkeratome for channel creation and completed at least three months of follow-up were included. Uncorrected visual acuity (UCVA), best spectacle corrected visual acuity (BSCVA), refractive outcome, Orbscan finding and corneal aberrations were assessed. Results: Three months postoperately, Low order aberration (defocus and astigmatism) decreased significantly (P<0.001). No statistically significant changes were detected in total RMS, trefoil, secondary trefoil and coma. Moreover, a statistically significant increase in quatrefoil, secondary coma, spherical aberration and secondary spherical was found. In term of visual outcomes, the mean UCVA (in LogMAR value) improved significantly from 0.75 ± 0.33 to 0.31 ± 0.23 and the mean BSCVA improved (from 0.31 ± 0.16 to 0.19 ± 0.15) (P<0.05). The mean spherical refractive error improved (from -1.37 ± 1.36 to 0.01 ± 2.47) and the mean cylindrical refractive error decreased significantly (from -3.8 ± 1.03 to -2.1 ± 1.27 (P<0.001)). Also, the mean keratometry value decreased from 47.61 ± 2.03 to 42.50 ± 2.76. Conclusion: KeraRing 355 implantation provided significant improvement in low order aberrations but was not effective in high order aberrations (HOA) in low/moderate keratoconus patients. However, UCVA, BCVA, spherical and cylindrical refractive error and keratometry results improved significantly.


Introduction
Keratoconus, the most common primary corneal ectasia, is a bilateral asymmetric corneal degeneration which accompanies with local corneal thinning and occurs mostly in inferior and central part of the cornea [1]. Initiating in puberty, Keratoconus (KCN) often progresses until fourth decade of life [2]. Affecting all ethnic groups equally, KCN usually causes high myopia and irregular astigmatism which results in poor quality of vision [2,3]. Based on disease severity, many treatment modalities exist including glasses and contact lenses for mild to moderate disease [2][3][4] while corneal graft preserved for more advanced disease [5]. High costs, need to long follow-ups, long periods for visual rehabilitation, risks of graft rejection or infection, wound dehiscence and suture-related problems make corneal grafts preserved for the last therapeutic choice by many ophthalmologists [6].
Initially, intracornial ring has been used to treat high myopia [15], but incision-related complication resulted in arrival of intrastromal segments to treat KCN in 2000 which achieved FDA approval in 2004 [14][15][16][17][18]. Different types of intrastromal segments include Intacs, Ferrara and Keraring [19]. Intacs segment consist of two semicircle PMMA-made parts with the arcuate length of 150 degrees and an axial hexagonal shape [20]. Ferrara segment shapes triangularly which helps to reduce stare and is made of PMMA and CQ acrylic [21]. Lack of variability in Ferrara and Intacs designs are of their disadvantages which resulted to the arrival of new generation of intrastromal segments named Keraring.

Methods
In this prospective interventional case series 22 eyes were included. All patients had mild to moderate Keratoconus. They underwent intrastromal Keraring 355 implantation at Bina eye hospital located in Teheran from October 2014 until October 2015. The study followed the tenets of the Declaration of Helsinki. Written informed consent was obtained in all cases. Keratoconus diagnosis was established by the corneal pachymetry readings and combination of computerized video keratography of the anterior and posterior corneal surfaces (Orbscan IIz) [34,35]. Patients with mild and moderate KCN based on the Amsler-Krumiech classification [36]. with visual acuity (UCVA) not better than 20/50, mean keratometry between 45 and 52 D, maintaining minimum central corneal thickness of 360 microns,nipple type keratoconic eyes with clear central cornea, age between 21 and 49 years with no other ocular and systemic disease other than keratoconus and contact lens intolerance were included in our study. Contact lens wear was discontinued three weeks prior to the exams. Exclusion criteria were history of vernal and atopic keratoconjunctivitis, positive pregnancy test, breast-feeding, history of keratorefractive surgery on the operative eye, history of corneal stromal disorders, patients with dry eye, immunosuppressive drugs users, advanced keratoconus with inferior corneal thinning less than 360 m, hyperopia, and patients with severe ocular and systemic pathologies. To prevent potential biases, surgery was done by just one surgeon (Kh.J). Data measurement was done by the same person and the same calibrated device before and after surgery. Surgery method remained the same for all patients. Patients were fully explained about the research purpose and steps. Informed written consent was taken from the patients. They were able to quit the study whenever they wanted.
In all eyes, we measured corneal derived wavefront analyses (Keratron-Scout, OPTIKON2000, Rome, Italy) and ocular aberrometry (Ocular Wavefront Analyzer, SCHWIND eye-tech-solutions GmbH & Co.KG), manifest refraction and visual acuity (UCVA and BSCVA respectively). Uncorrected visual acuity and best spectacle corrected visual acuity were measured using Snellen charts and transformed into logMAR units for statistical analysis. To evaluate the changes in corneal aberrations, High order optical aberrations including defocus error, astigmatism, comma error, Trefoil error, spherical error and quatrefoil error, secondary comma error, secondary Trefoil error, secondary astigmatism error and secondary spherical error were measured using Schwind Amaris aberrometer. All the measurements were repeated three months after surgery.

Surgical technique
Keeping a complete sterilized situation, the intervention was done by an expert surgeon (KH.J) under local anesthesia using propracaine hydrochloride 0.5%. As fully explained by Daxer 31, an 8.5 millimeter stromal pocket was made by a pocket maker microkeratome (Dioptex GmbH) at the depth of 300 microns. Microkeratome contained a suction ring and a surgical blade. First, suction ring was fixed over the cornea, and then a stromal pocket was made using surgical blade. The incision site was adjacent to the steep axis of the cornea. At the next step, suction ring was removed and Keraring 355 was implanted in the pocket. The surgeon chose the suitable thickness for Keraring 355 based on a pre-designed nomogram; a custom-surgeon nomogram [26]. The cornea was covered by a silicone-hydrogel bandage contact lens (Bausch & Lomb). Subsequently, patients were recommended to use topical chloramphenicol and betamethasone every 6 hours for 1 week and topical lubricants continued for one month.

Statistical analysis
All data were analyzed using SPSS 18. Mean, standard deviation and tables were used to describe the data. Comparing means of variables, Paired-T test were used. The normality testing for Gaussian distribution was performed using the shapiro-wilk normality test. In the case of non-Gaussian data distribution, the data were compared using the Wilcoxon matched-pairs signed rank test.
Maximum, minimum and mean of keratometric data decreased 7.00, 4.30 and 5.50 Diopter after surgery respectively. These results are in agreement with studies of Jadidi et al. [30], Jabbarvand et al. [33], Alio et al. [29] and Sansanayudh et al. [32]. The similar results in these studies can be related to similar 6 mm diameter and larger arc of rings. Many other studies found less decrease in Keratometric data which is probably because of smaller arcs and larger diameters of implanted rings [8,14,[32][33][34][35][36][37][38]. As mentioned by Jabbarvand et al. [29] and Alio et al. [25], it seems that complete rings could correct corneal curvature more effectively because of their stronger arc-shortening effect. Second order defocus error decreased 4.21 microns after intervention. This amount accords with spherical refractive error. Also, second order astigmatism decreased 2.48 microns which accords with cylindrical refractive error. Although clinically and statistically insignificant, Comma error increased a little after intervention. However it was consistent with some studies [8,[30][31][32].
Jabbarvand [29] and Haddad [28] found significant decrease for this type of error in their studies. The difference can be attributable to differences in mean of follow-up times and implanted rings, and difference in surgical technics, differences in stages of KCN between study population and different techniques to measure errors. Notwithstanding that in Jabbarvand study, patients with larger pupil than 5.5 millimeter were excluded from the study. Furthermore, In spite of secondary comma error, Trefoil error did not increase significantly, which is consistent with study by Jabbarvand et al. [29]. In the face of Vega-Estrada et al. [27] and Shayebak et al. [14] studies showing significant decrease in comma-like errors, our result shows little statistically insignificant increase in this type of error. This inconsistency can be attributable to different study population as just advanced KCN patients were included in the mentioned studies.
Considering primary spherical error, As Pinero et al. [19] mentioned, mechanical method to implant intrastromal segment can result in negative increase in spherical error, our study shows increase in a negative direction which accords with previous studies [25][26][27][28]. Secondary spherical error and quadrafoil also showed significant increase despite secondary astigmatism error which remained the same. Additionally, Spherical-like errors Showed significant increase which can be attributable to Keraring effect on corneal spherocity. We suggest use of larger diameter to decrease this effect.
At last, aberrometric parameters, RMS of all types of errors, showed insignificant decrease which is consistent with little improvement in BCVA. Our study had some limitations including small sample size, short follow-up duration, and lack of control group and mechanical method of surgery. In conclusion, this study demonstrated that there was a significant change after intrastromal Keraring 355 implantation and BCVA, spherical and cylindrical refractive error and keratometric data but complex and little effect on aberrometric parameters that is worthy of further study.