Complications and explantation reasons in intracorneal ring segments (ICRs) implantation: A systematic review

Title Page This is an Accepted Manuscript of an article published by Slack, Inc. in Journal of Refractive Surgery 35 (11) 740 – 751, on 2019, available at: https://doi.org/10.3928/1081597X-20191010-02 . It is deposited under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited, and is not altered, transformed, or built upon in any way. Title Complications and Explantation Reasons in Intracorneal Ring Segments (ICRS): A Systematic Review Authors Last Name First Name Academic Degree 1 Bautista-Llamas a María-José OD, PhD 2 Sánchez-González a María Carmen OD, PhD 3 López-Izquierdo a Inmaculada OD, PhD 4 López-Muñoz a Alfredo OD, PhD 5 Gargallo-Martínez a Beatriz OD, PhD 6 De-Hita-Cantalejo a Concepción OD, PhD 7 Sánchez-González a José-María OD, PhD a Department of Physics of Condensed Matter, Optics Area, University of Seville, Reina Mercedes S/N, Seville, Spain Corresponding author Name: Sánchez-González, José-María, OD, PhD, University of Seville Address: Reina Mercedes St., Physic Faculty, University of Seville, Seville, Spain Telephone number: +34 954 55 28 91 / +34 618 20 41 10 E-mail address: [email protected] 1 Clean Manuscript R2 1 Abstract 2 3 Purpose 4 To review the intraoperative and postoperative intracorneal ring segment complications and 5 to report the explantation rate among the available scientific literature. 6 Method 7 Three different databases, namely, PubMed, Web of Science and Scopus, were assessed 8 from January 1995 to June 2019. The keywords used were: ring, rings, ICRS (intracorneal 9 rings segments), segment, segments or Intacs, complication, explantation, explanted, retired 10 and removal. 11 Results 12 The selection process of this systematic review study is described in a flow diagram. A total 13 of 39 studies published between 1995 and 2019 were included in this systematic review. 14 Sixteen studies were case reports, twenty-one were case series studies and two were chart 15 analysis works. This study enrolled 1946 subjects, and 2590 eyes were included. 16 The postoperative complications described in most papers included migration, ring extrusion, 17 corneal thinning, corneal melting and some type of infective keratitis. These complications 18 together with glare, halos, fluctuating vision, neovascularization, foreign body sensation or 19 pain represented most of the causes. The percentage rate of explantation ranged from 0.5 20 up to 83.3%. If we analyze those articles with a high number of implantations (2124 eyes), 21 an explantation rate between 0% and 1.4% was obtained. 22 Conclusions 2 23 The complication rate and explantation ratio in segments of the intracorneal rings analyzed 24 in the available scientific literature are minimal. Therefore, patient selection, surgery planning 25 and postoperative follow-up are critical to the success of surgery. 26 Introduction 27 Intracorneal ring segments (ICRS) were used in the 1970s1 for low and moderate myopia 28 correction, and anterior cornea curvature flattening occurred by placing ICRS on the stroma. 29 Previous studies reported that it was a safe, effective and stable method to correct low 30 myopia.2 Currently, the method has been extended to various pathologies, such keratoconus 31 (KC), pellucid marginal degeneration (PMD) or iatrogenic corneal ectatic.3 Three types of 32 ICRS are available: INTACS ® (Addition Technology, Sunnyvale, CA, USA), Ferrara ® 33 (Mediphacos, Belo Horizonte, Brazil) and Kerarings ® (Mediphacos, Belo Horizonte, Brazil). 34 Classic ICRS channel creation by implanting the segments via mechanical dissection is 35 currently being replaced by femtosecond lasers. In addition to being less annoying to the 36 patient, the use of femtosecond lasers is faster and provides greater control of the depth, 37 width and centering of the tunnel as well as increased accuracy. In addition, epithelial tissue 38 changes are minimal, and recovery after surgery is faster.4,5 Channel creation by both 39 methods yields similar visual and refractive results. Nevertheless, increased intraoperative 40 complications occurred with mechanical ICRS implantation.6,7 41 ICRS involves intraoperative complications, such incomplete tunnel creation, cornea surface 42 perforation or anterior chamber perforation. In the first case, the complication can be 43 resolved by mechanical dissection. The perforation rates are low, which is one of the most 44 serious complications.8,9 Another intraoperative complication is vacuum loss, which occurs 45 during femtosecond suction; however, it is possible to recreate the same corneal plane and 46 the intrastromal channel. Among postoperative complications, segment migration can occur, 47 which may be due to an excessive ICRS width in a thin cornea. Coskunseven et al.8 and 48 Mounir et al.10 reported a high ring migration rate. ICRS implantation near the incision 49 implies a great risk of corneal melting, and ICRS should be explanted immediately in these 3 50 cases.11 Another reason for explantation reported in current literature is poor visual acuity or 51 fluctuations in visual quality. The first to describe an explantation for this reason was Asbell 52 et al.12 He got glare, halos and fluctuating vision. Recently other authors13–19 have also 53 reported poor visual acuity as a reason for explantation. 54 One of the main goals of ICRS surgery is to treat keratoconus or post-LASIK ectasia. . The 55 use of a permanent suture at the incision site and avoiding eye rubbing have been 56 proposed.20 Infection risk is noted with ICRS implantation. Multiple microorganisms have 57 been as causative agents of this complication, and both bacteria and fungi can cause 58 infectious keratitis. For example, Staphylococcus aureus21 appears in up to 25% of cases 59 followed by Pseudomonas sp. and Streptococcus pneumoniae among others.22,23 60 Several factors have been detected in relation to the onset of this complication, such as 61 previous traumas, use of contact lenses, or systemic diseases, such as diabetes mellitus.24 62 The most efficient method to treat infectious keratitis after ICRS implantation is topical 63 antibiotic therapy. Bourcier et al.25 reported that topical antibiotic therapy alone was sufficient 64 to treat the infection. On the other hand, in some publications, ICRS explantation was 65 considered as the first therapeutic option to treat this complication. Deep corneal 66 neovascularization is another complication that can be caused by the implant and is not 67 associated with the surgical wound. Treatment with topical corticoid agents and surgical 68 removal of the ring may induce vessel regression.26 69 This systematic review aims to report intraoperative and postoperative intracorneal ring 70 segment complications and to report explantation rates among the available scientific 71 literature. 72 73 Methods 74 This review is registered at the PROSPERO International prospective registry. The study 4 75 was performed according to the PRISMA statement recommendations. PubMed, Web of 76 Science and Scopus data based were searched from January 1995 to June 2019. The 77 keywords used were ring, rings, ICRS (intracorneal rings segments), segment, segments or 78 Intacs, complication, explantation, explanted, retired or removal. Experts identified and 79 evaluated the articles selected according by inclusion and exclusion criteria. Two 80 independent reviewers extracted and selected studies. Duplicate articles were assessed by 81 authors. Among the inclusion criteria were: (1) Case reports, case series, chart analysis and 82 randomized controlled trials reporting intraoperative and postoperative complication in ICRS 83 implantation; (2) ICRS explantation papers as well as the reasons; (3) There was no 84 restrictions on publication type (conference abstract versus full article) and (4) abstracts 85 were included only if they fulfill our eligibility criteria and if no subsequent study has been 86 published. Among the exclusion criteria: (5) We excluded narrative reviews, systematic 87 reviews, letters to the editor and correspondences; (6) animal studies were also excluded 88 and (7) non-English publication and non-index publication. The authors designed the tables 89 to extract the study data. 90 91 Systematic review data were extracted according to studies characteristics and main 92 outcomes measures. Among the first part, extracted data items included (1) authors and 93 publication year; (2) study design (case report or retrospective case series); (3) conflict of 94 interest declaration (yes or no; which, if yes); (4) subject inclusion and exclusion criteria; (5) 95 period of total patient follow-up from the first complication to its total resolution expressed in 96 weeks; (6) percentage of male subjects involved in the study; (7) number of subjects and 97 eyes involved in the study; (8) ICRS type, manual or femtosecond implantation and ICRS 98 brand and / or design; (9) number of segments per eye, i.e., one, two or both numbers were 99 provided if one and two ICRS implantations were reported among different subjects; and 100 (10) mean subject age expressed in years. Amongst the outcome’s measures, the following 101 data items were reported: (11) previous eye history, such previous treatments, ocular 102 pathologies or eye surgeries; (12) intraoperative and (13) postoperative complications were 5 103 reported and the percentage of total eyes in this study were expressed in brackets; (14) 104 explantation rate and (15) explantation reasons. Finally, (16) treatment used to resolve the 105 complications was recorded. In this case, the treatment reported was the one that was 106 ultimately effective. In-between unsuccessful treatments were avoided. 107 To determine the individual studies risk of bias, two reviewers with adequate reliability 108 worked independently and blindly to create a summary chart (Table 1) based on the Quality 109 Assessment Tool for Case Series Studies from the National Heart, Lung, and Blood 110 Institute.27 For disputes between the two reviewers, a third non-blinded reviewer resolved the 111 issue. Questions included in the tool were as follows: (1) Was the study question or objective 112 clearly stated?, (2) Was the study population clearly and fully described, including a case 113 definition?, (3) Were the cases consecutive?, (4) Were the subjects comparable?, (5) Was 114 the intervention clearly described?, (6) Were the outcome measures clearly defined, valid, 115 reliable, and implemented consistently across all study participants?, (7) Was the length of 116 follow-up adequate?, (8) Were the statistical methods well described? and (9) Were the 117 results well described? This analysis did not result in the elimination of any article. Articles 118 with a high risk of bias had a lower weight for data synthesis. The primary summary 119 measures used in this systematic review were incidence percentage of complications and 120 explantations among all included studies. Furthermore, the average changes in terms of 121 visual acuity and mean keratometry were also reported. Finally, we also included ICRS 122 design and implantation technique with more complications and common treatments used in 123 complication resolution as summary measures. 124 125 Results 126 This systematic review study selection process is described by a flow diagram (Figure 1). A 127 total of 39 studies published between 1995 and 2019 were included in this systematic 128 review. Sixteen studies were case reports, twenty-one were case series studies and only two 6 129 were chart analysis works. Only three studies reported conflicts of interest. Chhadva et al.17 130 reported that Dr. Yoo is an AMO (Advanced Medical Optics) consultant. Said et al.28 131 reported that Dr. Ibrahim is a Carl Zeiss Meditec consultant. Nguyen et al.29 reported that Dr. 132 Hersh receives speaker fees from Addition Technology, Inc. The inclusion criteria included 133 subjects with grade I, II, and grade III keratoconus; residual myopia post LASIK; ICRS 134 explantation; keratitis infection; post LASIK ectasia; contact lens intolerance; ICRS 135 migration; atopic keratoconus or ICRS surgery simultaneously with crosslinking. Regarding 136 exclusion criteria, most studies omitted ICRS implantation cases without complications. 137 Others authors excluded studies for different reasons: corneal scarring30, leucoma31, 138 keratitis8,32, non-INTACS ICRS15, manual ICRS implantation17 or corneal hydrops10,28 in 139 grade IV keratoconus. The post-surgery follow-up ranged from two weeks to two hundred 140 and forty weeks. The mean follow-up for the reported studies was 56.9 weeks. This 141 systematic review enrolled 1946 subjects. In total, 62.34% of these subjects were male, and 142 2590 total eyes were included. The mean age of subjects was 33.45 years. Many of the 143 studies report that surgery was performed manually or with a femtosecond and the type of 144 segment but do not report the percentage of each type of surgery. Therefore, a quantitative 145 analysis could not be performed using the studies. Detailed study characteristics were 146 reported in Table 2. 147 148 Table 3 describes the complications caused by the ICRS and the explantation provided in 149 the revised studies. In relation to the previous ocular history of the patients, we found: eight 150 articles with post-LASIK ectasia.14,15,19,22,29,30,33,34 Six articles in low and moderate myopia. 151 12,14,18,23,24,35 Two with pellucid marginal degeneration.14,33 And only one article with 152 keratoplasty. 14 In addition, atopic asthma and blepharoconjunctivitis,36 lagophthalmos and 153 dry eye,37 herpetic keratitis38 and blepharitis39 were described in the previous eye history. 154 7 155 Intraoperative complications were described in five publications: some epithelial damage at 156 the incision site;35 perforation of the anterior chamber (only 5% of the 20 eyes);20 difficult 157 insertion in one case and intraoperative suction loss;28 incomplete tunnel creation, 158 misdirection of the ring segment, perforation into anterior chamber, decentration of ring 159 segments, inverted implanted rings, broken ring segments, broken and orifice of ring;10 160 galvanometer lag error and endothelial perforation8. 161 Postoperative complications were described in most papers: migration, ring extrusion, 162 corneal thinning, corneal melting and type of infective keratitis (bacterial, Staphylococcus 163 aureus, Streptococcus mitis, Staphylococcus epidermidis, annular herpetic and Aspergillus 164 fumigatus). These complications together with glare, halos, fluctuating vision, 165 neovascularization, foreign body sensation or pain account for 100% of the rings explanted 166 in 50% of the articles. The percentage rate of explantation ranged from 0.5 up to 83.3%. If 167 we analyze those articles with a high number of implantations 8,10,28,33,40 (2124 eyes), an 168 explantation rate between 0% and 1.4% was obtained. 169 170 According ICRS type reviewed, Ferrara – Keraring ICRS reported a one percent explantation 171 rate, and INTACS reported a nineteen percent explantation rate. Only four papers reported 172 no explantation in the case.28,38,41,42 The most commonly used treatments are antibiotics in 173 those articles in which it is described. Some articles do not report it, and two of the articles 174 recommended suture of the incision.42,17 175 176 Risk of bias assessment within the studies was grouped into three outcome levels: low 177 evidence level (between zero and three yeses), medium evidence level (between four and 178 six yeses) and high evidence level (between seven and nine yeses). The following studies 179 obtained a low evidence level: Quantock et al.43, Asbell et al.12, Bourges et al.23, McAlister et 180 al.36, Galvis et al.37, Cosar et al.11, Ibáñez-Alperte et al.44, Chalasani et al.45, Rayward et al.38, 8 181 Jarade et al.42, García de Oteyza et al.46, Oatts et al.18, Chan and Hersh19 and Elbaz et al.47. 182 The following studies obtained a medium evidence level: Shehadeh et al.22, Güell et al.35, 183 Alió et al.48, Hofling-Lima et al.24, Ferrer et al.14, Mulet et al.33, Kugler et al.40, Shihadeh49 Bali 184 et al.15, Yeung et al.16, Neira et al.39, López-Ferrando and Medrano-Ruiloba41 and Nguyen et 185 al.29. The following studies obtained a high evidence level: Kwitko and Severo50, 186 Kanellopoulus et al.20, Carrasquillo et al.30, Zare et al.31, Alió et al.13, Coskunseven et al.8, 187 Chhadva et al.17, Said et al.28, Abdelmassih et al.32, Mounir et al.10, Iqbal et al.51 and 188 Tabatabaei et al.34. 189 190 191 Discussion 192 Mechanical technique complications comprise anterior or posterior perforation by manual 193 spreader, epithelial defects, decentration, and incision enlargement to the limbus or central 194 cornea due to surgeon manipulation. Most cases of extrusion and final removal of ICRS 195 were experimental in manual ICRS implantation. During ICRS implantation surgery, 196 keratocyte activation52 and apoptosis are noted. Twa et al.53 demonstrated lipid formation 197 and increased keratocyte density following ICRS implantation. Kugler et al.40 postulated that 198 additional trauma to the incision and tunnel results in increased keratocyte apoptosis, major 199 tissue degradation, and a subsequently increased number of complications, such corneal 200 melting. Femtosecond laser ICRS channel creation is less aggressive. Femtosecond laser is 201 associated with reduced complications for corneal melting. Corneal confocal microscopy has 202 been used for assessment after manual54 and femtosecond55 ICRS implantation; however, to 203 our knowledge no studies have been reported keratocyte activation scores in femtosecond 204 versus manual techniques. 205 Nevertheless, the femtosecond laser introduced new complications to ICRS. All these 206 complications were intraoperative, including incomplete channel creation, galvanometer lag 207 error or vacuum loss. Incomplete tunnel creation was solved by completing the channel 15 359 after laser in situ keratomileusis. J Refract Surg. 2004;20(4):349-355. 360 36. McAlister JC, Ardjomand N, Ilari L, Mengher LS, Gartry DS. Keratitis after intracorneal 361 ring segment insertion for keratoconus. J Cataract Refract Surg. 2006;32(4):676-678. 362 doi:10.1016/j.jcrs.2005.09.026 363 37. Galvis V, Tello A, Delgado J, Valencia F, Gómez AJ, Diaz LA. Late bacterial keratitis 364 after intracorneal ring segments (Ferrara ring) insertion for keratoconus. Cornea. 365 2007;26(10):1282-1284. doi:10.1097/ICO.0b013e3181506142 366 38. Rayward O, Arriola-Villalobos P, Cuiña-Sardiña R, Diaz-Valle D, Benítez-Del-Castillo 367 JM, García-Feijoo J. Annular Herpetic Keratitis After Intracorneal Ring Segment 368 Implantation. Cornea. 2011;30(11):1286-1286. doi:10.1097/ICO.0b013e31821c9bb8 369 39. Neira W, Krootila K, Holopainen JM. Atopic dermatitis is a risk factor for intracorneal 370 ring segment extrusion. Acta Ophthalmol. 2014;92(6):e491-2. doi:10.1111/aos.12377 371 40. Kugler LJ, Hill S, Sztipanovits D, Boerman H, Swartz TS, Wang MX. 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Monteiro T, Alfonso JF, Franqueira N, Faria-Correia F, Ambrósio R, Madrid-Costa D. 423 Predictability of Tunnel Depth for Intrastromal Corneal Ring Segments Implantation 424 Between Manual and Femtosecond Laser Techniques. J Refract Surg. 425 2018;34(3):188-194. doi:10.3928/1081597X-20180108-01 426 58. Monteiro T, Alfonso JF, Freitas R, et al. Comparison of Complication Rates between 427 Manual and Femtosecond Laser-Assisted Techniques for Intrastromal Corneal Ring 428 Segments Implantation in Keratoconus. Curr Eye Res. July 2019:1-8. 429 doi:10.1080/02713683.2019.1635165 430 59. Hashemi H, Nabavi A, Bayat R, Mohebbi M. Additional Intrastromal Corneal Ring 431 Segments in Keratoconus. Cornea. 2018;37(5):574-579. 432 doi:10.1097/ICO.0000000000001519 433 60. Piñero DP, Alió JL, El Kady B, Pascual I. Corneal aberrometric and refractive 18 434 performance of 2 intrastromal corneal ring segment models in early and moderate 435 ectatic disease. J Cataract Refract Surg. 2010;36(1):102-109. 436 doi:10.1016/J.JCRS.2009.07.030 437 61. Kaya V, Utine CA, Karakus SH, Kavadarli I, Yilmaz ÖF. Refractive and Visual 438 Outcomes After Intacs vs Ferrara Intrastromal Corneal Ring Segment Implantation for 439 Keratoconus: A Comparative Study. J Refract Surg. 2011;27(12):907-912. 440 doi:10.3928/1081597X-20110906-03 441 19 442 Figure legends 443 Figure 1. Study selection process according to the PRISMA statement 444 Table legends 445 Table 1. Quality Assessment Tool for Case Series Studies 446 Table 2: Study characteristics and patient population 447 Table 3: Data extraction for complications and explantations 448 Table 1 Table 1. Quality Assessment Tool for Case Series Studies Author (year) Q 1 Q 2 Q 3 Q 4 Q 5 Q 6 Q 7 Q 8 Q 9 Quantock et al.39 (1995) Yes Yes No No Yes No No No No Asbell et al.31 (1999) Yes Yes No No Yes No No No No Bourges et al.16 (2003) Yes Yes No No Yes No No No No Shehadeh et al.15 (2004) Yes Yes NA NA Yes No No NA Yes Güell et al.33 (2004) Yes No No Yes Yes No Yes Yes Yes Alió et al.44 (2004) Yes Yes No Yes Yes Yes No No Yes Hofling-Lima et al.17 (2004) Yes Yes No Yes No No Yes No No Kwitko and Severo48 (2004) Yes Yes No Yes Yes Yes Yes Yes Yes Kanellopoulus et al.13 (2006) Yes Yes No Yes Yes Yes Yes Yes Yes McAlister et al.34 (2006) NA CD NA NA Yes Yes Yes NA NA Galvis et al.35 (2007) NA CD NA NA Yes Yes Yes NA NA Carrasquillo et al.24 (2007) Yes Yes NR Yes Yes Yes Yes Yes Yes Zare et al.25 (2007) Yes Yes NR Yes Yes Yes Yes Yes Yes Cosar et al.11 (2009) NA CD NA NA Yes Yes Yes NA NA Ibáñez-Alperte et al.40 (2010) Yes Yes NA NA No No NR NA No Alió et al.49 (2010) Yes Yes Yes Yes Yes Yes Yes Yes Yes Ferrer et al.29 (2010) Yes No No NR Yes Yes Yes NA Yes Mulet et al.30 (2010) Yes Yes No NA Yes Yes No NA Yes Chalasani et al.41 (2010) NA CD NA NA Yes Yes Yes NA NA Kugler et al.45 (2011) Yes No No No Yes No Yes NA Yes Rayward et al.36 (2011) NR No NA NA No No NR NA No Coskunseven et al.8 (2011) Yes Yes No Yes Yes Yes Yes No Yes Shihadeh46 (2012) Yes Yes NA NA No No Yes NA Yes Bali et al.27 (2012) Yes Yes No No Yes Yes Yes No Yes Yeung et al.47 (2013) Yes Yes No No Yes Yes Yes NA Yes Jarade et al.38 (2013) Yes No No Yes Yes NR CD NA NR Neira et al.12 (2014) NR Yes No Yes Yes Yes NR NA Yes Chhadva et al.21 (2015) Yes Yes No Yes Yes Yes Yes NA Yes López-Ferrando and Medrano-Ruiloba37 (2016) NR No No No Yes Yes Yes NA Yes Said et al.22 (2016) Yes Yes Yes Yes Yes Yes Yes Yes Yes Abdelmassih et al.26 (2017) Yes Yes Yes Yes Yes Yes Yes Yes Yes García de Oteyza et al.42 (2017) NA CD NA NA Yes NA NA NA Yes Oatts et al.32 (2017) NA CD NA NA Yes NA NA NA Yes Chan and Hersh28 (2017) NA CD NA NA Yes NA NA NA Yes Mounir et al.10 (2018) Yes Yes Yes Yes Yes Yes Yes Yes Yes Elbaz et al.43 (2018) NA CD NA NA Yes NA NA NA Yes Nguyen et al.23 (2019) Yes No Yes NA Yes No NA NA Yes Iqbal et al.50 (2019) Yes Yes Yes Yes Yes Yes Yes Yes Yes Tabatabaei et al.51 (2019) Yes Yes Yes Yes No Yes Yes Yes Yes Question 1: Was the study question or objective clearly stated?; Question 2: Was the study population clearly and fully described, including a case definition?; Question 3: Were the cases consecutive?; Question 4: Were the subjects comparable?; Question 5: Was the intervention clearly described?; Question 6: Were the outcome measures clearly defined, valid, reliable, and implemented consistently across all study participants?; Question 7: Was the length of follow-up adequate?; Question 8: Were the statistical methods well-described?; Question 9: Were the results well-described?; Q: Question; CD: Cannot determine; NA: Not applicable; NR: Not reported; Rater #1 initials: MJBLL; Rater #2 initials: JMSG. Table 2 Author (year) Design Confli ct Inclusion criteria Exclusion criteria Follow-up (weeks) Subjects (% Male) N (eyes) ICRS Type ICRS per eye Age Quantock et al.39 (1995) CR No NA NA 32 1(100%) 1 Manual Keraring 1 46 Asbell et al.31 (1999) CR No NA NA 40 1 (NR) 1 Manual Keraring 2 28 Bourges et al.16 (2003) CR No NA NA 240 1 (0%) 1 Manual INTACS 2 41 Shehadeh et al.15 (2004) CR No Ectasia No complications 12 1 (100%) 1 Manual INTACS 2 53 Güell et al.33 (2004) CS No Myopia PL NA 12-40 8 (NR) 13 Manual INTACS 2 NR Alió et al.44 (2004) CA No ICRS explanted NA 48 4 (NR) 5 Manual INTACS 1/2 32, 51 (50% NR) Hofling-Lima et al.17 (2004) CS No Keratitis NA 88 8 (37.5%) 8 Ferrara (87.5%) INTACS (12.5%) NR 32 Kwitko and Severo48 (2004) CS No KC NA 52 47 (NR) 51 Manual Ferrara 2 NR Kanellopoulus et al.13 (2006) CS No KC NA 48 15 (40%) 20 Manual INTACS 2 30.2 McAlister et al.34 (2006) CR No NA NA 3 1(100%) 1 Manual Ferrara 2 34 Galvis et al.35 (2007) CR No NA NA 16 1(0%) 1 Manual Ferrara 2 42 Carrasquillo et al.24 (2007) CS No KC and PLE Corneal scarring 6-49 29(55%) 33 50% Manual 50% FS INTACTS 1/2 39 Zare et al.25 (2007) CS No KC and CLI Leucoma 24 22 (77%) 30 FS INTACTS 1/2 26 Cosar et al.11 (2009) CR No NA NA 144 1 (100%) 1 Manual INTACS 2 33 Ibáñez-Alperte et al.40 (2010) CR No KC NA ≈7 1 (NR) 1 Manual INTACS 2 36 Alió et al.49 (2010) CS No KC and ICRS explanted NR 24 21 (NR) 21 Manual / FS INTACTS and Keraring 1/2 36 Ferrer et al.29 (2010) CS No ICRS explanted NR 336 47 (51%) 57 Manual / FS INTACTS and Keraring 1/2 37 Mulet et al.30 (2010) CS No Keratitis NR 4 149 (59%) 212 Manual / FS INTACTS and Keraring 1/2 35 Chalasani et al.41 (2010) CR No NA NA 12 1 (0%) 2 Ferrara 1 40 Kugler et al.45 (2011) CS No Ectasia Non complications ≈28 279 (NR) 279 FS INTACS 1/2 44.25 Rayward et al.36 (2011) CR No KC G II NA 2 1 (100%) 1 NR 1 26 Coskunseven et al.8 (2011) CA NR KC G II – III CT > 350 µm Herpes or keratitis NR 531 (NR) 850 FS Keraring NR 28.32 Shihadeh46 (2012) CR No KC moderate myopia NA ≈ 20 1 (100%) 2 NR 1 34 Bali et al.27 (2012) CS No KC (4) Ectasia (6) Non INTACTS surgeries 48 9 (66.6%) 10 FS INTACTS 1/2 44.5 Yeung et al.47 (2013) CS No KC NA 12 3 (66.6%) 6 INTACTS 2 21.6 Jarade et al.38 (2013) CS No ICRS Migration No surgery complications 24 2 (NR) 2 INTACTS / Keraring 1 NR Neira et al.12 (2014) CS NR Atopic Dermatitis AKC No surgery complications NR 5 (40%) 5 Manual INTACS 1/2 32.6 Chhadva et al.21 (2015) CS Yes a KC Manual Implantation 48.5 8 (50%) 10 FS INTACTS 2 38 López-Ferrando and Medrano-Ruiloba37 (2016) CS NR KC NA 36-168 35 (NR) 50 Manual Ferrara 1/2 NR Said et al.22 (2016) CS Yes b KC, CLI CT> 450 μm Haze Hydrops Infection 24 100 (43%) 160 FS Keraring 1/2 21,77 Abdelmassih et al.26 (2017) CS No ICRS + CXL Keratitis or IOL 24-208 12 (83.35%) 17 FS Keraring and INTACS 1/2 12.3 García de Oteyza et al.42 (2017) CR No NA NA NR 1 (100%) 1 FS Ferrara 2 13 Oatts et al.32 (2017) CR No NA NA 84-240 2 (50%) 3 Manual INTACS 2 33 Chan and Hersh28 (2017) CR No NA NA 8-104 3 (33%) 3 FS INTACS 1/2 49,67 Mounir et al.10 (2018) CS No KC G II – III CT > 350 μm PLE Hydrops KC G IV 52 417 (49,4%) 623 FS Keraring 1/2 22,27 Elbaz et al.43 (2018) CR No NA NA 16 1(100%) 1 Manual Ferrara 2 37 Nguyen et al.23 (2019) CS Yes c KC PLE NA NR 31 (71,4%) 35 FS INTACTS 1/2 41 Iqbal et al.50 (2019) CS No KC G I, II or III NA 72 37(NR) 63 FS Keraring 1/2 9-17 Tabatabaei et al.51 (2019) CR NR NA NA 26 11 (72,7%) 11 Keraring, Intacs, Myoring and AICI NR 29 ICRS: Intracorneal ring segments; CR: Case report; NA: Not applied; CS: Case series; NR: Not Reported; PL: Post LASIK; CA: Chart analysis; KC: Keratoconus; PLE: Post-Lasik ectasia; FS: Femtosecond; CLI: Contact lens intolerant; G: Grade; CT: Corneal thickness; AKC: Atopic keratoconjunctivitis; CXL: Crosslinking; IOL: Intraocular lens; AMO: Advanced Medical Optics. a Dr. Yoo is AMO consultant. b Dr. Ibrahim is Carl Zeiss Meditec Consultant. c Dr. Hersh receives speaker fees from Addition Technology, Inc. Table 3 Table 3: Data extraction for complications and explantations Author (year) Previous eye history Intraoperative complications Postoperative complications Explantation Yes / No (%) Explantation reason Treatment used Quantock et al.39 (1995) Nonfunctional eye or glaucoma None Crescentic iron line Yes (100%) Study protocol NR Asbell et al.31 (1999) Myopia None Faint haze in stromal channel Yes (100%) Glare, halos, fluctuating vision Tobramycin / dexamethasone Bourges et al.16 (2003) Myopia None Lamellar channel deposits Yes (100%) Stromal thinning, extrusion Bacitracin / polyvinyl alcohol Shehadeh et al.15 (2004) PLE None Bacterial keratitis Yes (100%) Staphylococcus Cefamezin / gentamicin Güell et al.33 (2004) Residual myopia PL Epithelial damage Progressive stromal lysis Yes (7.7%) Progressive stromal lysis NR Alió et al.44 (2004) KC None Migration (100%), partial extrusion (80%), moderate melting (80%), corneal thinning (20%) Yes (100%) Segment migration and partial extrusion NR Hofling-Lima et al.17 (2004) KC and low myopia None Infectious keratitis Yes (62.5%) Infectious keratitis NR Kwitko and Severo48 (2004) KC None Ring decentration (3.9%), extrusion (19.6%), disciform keratitis (1.9%), bacterial keratitis (1.9%) Yes (3.9%) Extrusion after trauma NR Kanellopoulus et al.13 (2006) KC AC Perforation (5%) Movement, exposure and corneal thinning (30%), CM and infiltrate (5%) Yes (35%) Repeated exposure and / or corneal thinning NR McAlister et al.34 (2006) KC Atopic asthma and BC None White infiltrate and deposit formation Yes (100%) Infection keratitis Dexamethasone chloramphenicol Galvis et al.35 (2007) KC, lagophthalmos and dry eye None Staphylococcus aureus Yes (100%) Infection keratitis Vancomycin, imipenem, amphotericin B and moxifloxacin Carrasquillo et al.24 (2007) KC and PLE None Neovascularization and fungal infection Yes (3%) Herpes simplex keratitis NR Zare et al.25 (2007) KC None ICRS exposure Yes (13%) Extrusion (13%), bacterial keratitis (3%) NR Cosar et al.11 (2009) KC None Neovascularization Yes (100%) Neovascularization FML / ciprofloxacin Ibáñez-Alperte et al.40 (2010) NR None Corneal ulcer and hypopyon Yes (100%) Extrusion / bacterial keratitis Vancomycin / ceftazidime Alió et al.49 (2010) Keratoconus None ICRS extrusion and vascularization Yes (100%) Extrusion (33%), VA (57%), neovascularization (10%) NR Ferrer et al.29 (2010) KC (79%), PLE (12%), PMD (5%), KP (2%) and myopia (2%) None ICRS migration, keratitis, CM and corneal perforation Yes 100% Extrusion (48%), VA (38%), keratitis (7%), CM (5%) and perforation (2%) NR Mulet et al.30 (2010) KC (81%), irregular astigmatism (10%), PLE (5%) and PMD (4%) None Streptococcus mitis and aureus Yes (1%) Infection keratitis Ceftazidime / amikacin, ofloxacin / vancomycin Chalasani et al.41 (2010) Keratoconus None Staphylococcus epidermidis Yes (50%) Infection keratitis Vancomycin / tobramycin Kugler et al.45 (2011) NR None Corneal melt (1.4%) Yes (1.4%) Incision overlapping BCL / steroids Rayward et al.36 (2011) RGP CL and herpetic Keratitis None Annular herpetic keratitis No (100%) NA Acyclovir / antibiotics Coskunseven et al.8 (2011) None Incomplete channel (2.6%), galvanometer lag (0.6%), endothelial perforation (0.6%), channel entrance (0.2%), vacuum (0.2%) ICRS migration (0.8%), corneal Melting (0.2%) and corneal abscess (0.1%) Yes (0.5%) Melting corneal Antibiotics Shihadeh46 (2012) CL intolerance None Aspergillus fumigatus Yes (100%) Microbiological infection Gatifloxacin / itraconazole Bali et al.27 (2012) KC and PLE None Epithelial ingrowth (20%) Yes (100%) Poor VA / epithelial ingrowth NR Yeung et al.47 (2013) NR None ICRS migration (33.3%) Yes (83%) Poor VA / ICRS Migration CXL Jarade et al.38 (2013) NR None ICRS Migration No (100%) NA Incision Suturing Neira et al.12 (2014) Atopic Dermatitis, AKC, blepharitis and GPC None Corneal melting (100%) Yes (100%) Corneal melting Topical steroids Chhadva et al.21 (2015) NR None VA (80%), overlapping and VA (20%) Yes (100%) Overlapping and Visual quality Incision suturing / PKP López-Ferrando and Medrano-Ruiloba37 (2016) Eye Rubbing None Late breaks (6%), ICRS migration (4%), overlapping (2%) No (100%) NA NR Said et al.22 (2016) KC Vacuum loss ICRS broke / inverted ICRS No (100%) NA Moxifloxacin / prednisolone Abdelmassih et al.26 (2017) KC None Vascularization and corneal thinning Yes (5,9%) ICRS migration Tobramycin / gatifloxacin García de Oteyza et al.42 (2017) KC None Whitish infiltrate, hypopyon, CM Yes (100%) Staphylococcus aureus keratitis Vancomycin, ceftazidime, moxifloxacin, tobramycin, dexamethasone and loteprednol Oatts et al.32 (2017) Myopia None Epithelial defect, thinned cornea and extrusion Yes (100%) FBS, photophobia and VA NR Chan and Hersh28 (2017) KC and PLE NR VA, diplopia and haloes Yes (83,3%) Low vision quality Antibiotic and corticosteroid Mounir et al.10 (2018) KC Vacuum loss, incomplete tunnel creation, ICRS migration, AC perforation, inverted ICRS, broken ICRS ICRS migration, extrusion, Incision opacification, steroid-induced glaucoma, infectious keratitis, crystalline sterile keratitis, CM Yes (0,8%) ICRS migration, infectious keratitis and perforation into the anterior chamber Moxifloxacin / prednisolone Elbaz et al.43 (2018) KC None Spontaneous in situ breakage Yes (100%) Pain, redness and FBS Antibiotics and corticosteroid Nguyen et al.23 (2019) KC and PLE NR Microbial keratitis, photophobia, FBS and VA Yes (6%) Refractive / topographic considerations Gatifloxacin and vancomycin Iqbal et al.50 (2019) KC NR Migration (1,6%), extrusion (4,7%) and KC progression (6,4%) Yes (6,3%) ICRS migration and Extrusion Gatifloxacin / prednisolone Tabatabaei et al.51 (2019) PLE NR Keratitis Yes (100%) Keratitis Cefazolin / amikacin / vancomycin NR: Not reported; PLE: Post-LASIK ectasia; PL: Post LASIK; KC: Keratoconus; AC: Anterior chamber; CM: Corneal melting; BC: Blepharoconjunctivitis; ICRS: Intracorneal ring segment; FML: Fluorometholone; VA: Visual acuity; PMD: Pellucid marginal degeneration; KP: Keratoplasty; BCL: Bandage contact lens; RGP: Rigid gas permeable; CL: Contact lens; CXL: Crosslinking; AKC: Atopic keratoconus; GPC: Giant papillary conjunctivitis; PKP: Penetrant keratoplasty; FBS: Foreign body sensation Figure 1 Click here to access/download;Figure with Hyperlink;Figure 1.tif