CLINICAL SCIENCE
Evaluation of a Toric Implantable Collamer Lens After Corneal Collagen Crosslinking in Treatment of Early-Stage Keratoconus: 3-Year Follow-up Mohamed Shafik Shaheen, MD, PhD,* Mohamed El-Kateb, MD, PhD,* Mohamed A. El-Samadouny, MD, PhD,* and Hussam Zaghloul, MD†
Purpose: The aim of this study was to assess the predictability, efficacy, safety, and stability in patients who received a toric implantable collamer lens (TICL) after collagen crosslinking in early-stage keratoconus.
Methods: This prospective interventional case series study was conducted at the Alexandria Main University hospitals, University of Alexandria, Egypt. Sixteen eyes underwent implantation of a TICL (STAAR Surgical Inc) after crosslinking. The mean spherical refraction was 25.98 6 4.39 diopters (D) (range, 20.50 to 214.50 D), and the mean cylinder was 24.91 6 1.51 D (range, 22.50 to 27.75 D). Uncorrected distance visual acuity (UDVA), manifest and cycloplegic refraction, corrected distance visual acuity (CDVA), vault, intraocular pressure, and endothelial cell count (using specular microscopy) were evaluated during a 3-year follow-up. Results: The mean Snellen decimal CDVA improved from 0.56 6
0.13 (range, 0.40–0.80) preoperatively to 0.89 6 0.17 (range, 0.60– 1.20) at 3 years of the follow-up (P , 0.0001). The mean UDVA also improved significantly from 0.63 6 0.14 before ICL implantation to 0.88 6 0.18 after 3 years of the follow-up (P , 0.001). At 3 years, the mean spherical and cylindrical manifest refractions were 0.00 6 0.18 D and 20.05 6 0.14 D, respectively. At the end of the follow-up, the vault was 509.75 6 141.47 mm (range, 320–900) and the intraocular pressure was 11.94 6 1.12 mm Hg. No complications occurred during the surgical procedures. No eye needed explantation or repositioning of the TICL. The endothelial cell count loss after 3 years was 28.98%.
Conclusions: Correction of spherical and cylindrical refractive errors in keratoconic eyes by TICL implantation 12 months after crosslinking gave significantly promising outcomes, particularly in the astigmatic component of refraction. Key Words: keratoconus, crosslinking, toric implantable collamer lens (Cornea 2014;33:475–480) Received for publication December 6, 2013; revision received January 13, 2014; accepted January 14, 2014. Published online ahead of print March 11, 2014. From the *Department of Ophthalmology, University of Alexandria, Alexandria, Egypt; and †Armed Forces Hospitals, Alexandria, Egypt. The authors have no funding or conflicts of interest to disclose. Reprints: Mohamed S. Shaheen, University of Alexandria, PO Box 27, Ibrahimia, Alexandria 21321, Egypt (e-mail: m.shafi[email protected]). Copyright © 2014 by Lippincott Williams & Wilkins
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K
eratoconus is a corneal degeneration characterized by bilateral conical protrusion and corneal thinning.1 The average age of onset of keratoconus is the twenties.2 The course of the disease varies from slight irregular astigmatism to severe visual impairment because of increasing protrusion and subepithelial scarring.3 Because of the young age of the patients, keratoconus often has a significant negative effect on the quality of life.2 The results of currently available treatment options are not encouraging because the treatments do not stop the progression of keratoconus. Thus, because of its progressive nature, keratoconus was the most frequent reason for keratoplasty to be performed in the past 3 decades.4 Keratoconus leads to biomechanical alterations, and its specific cause is not known.5,6 The biomechanical characteristics of the cornea result from the collagen scaffold and collagen compound and their bonding with the collagen fibrils. The 3-dimensional configuration of the collagen lamella fundamentally codetermines the resistance of the cornea.7,8 Biochemical and immunohistochemical studies of matrix proteoglycans show that differences exist between normal and keratoconic corneas.5 Enzymatic alterations with an increased expression of lysosomal and proteolytic enzymes,5,7 decreased concentration of protease inhibitors,5,7 decreased thickness,5 and modified configuration of the stromal collagen lamella7 have been observed. A photooxidative collagen crosslinking technique using riboflavin and ultraviolet (UV)-A light was developed to counteract the progressive corneal thinning and thus the progression of keratoconus. By crosslinking, additional covalent binding between collagen molecules can be achieved, which stabilizes the collagen scaffold and changes several tissue properties.4 An increase in the corneal stiffness and enhanced resistance against proteolytic enzymes caused by the riboflavin and UV-A light was shown in human eyes.9 The crosslinking effect is not distributed homogenously over the corneal depth. The stiffening effect is concentrated in the anterior 200 to 300 mm of the cornea because of the high absorption of UV light in this area.10 The Implantable Collamer Lens (ICL; STAAR Surgical, Nidau, Switzerland) is a posterior chamber phakic intraocular lens, which has been reported not only for its superiority in postoperative visual performance but also for its safety and effectiveness in the correction of moderate to high myopic astigmatism.11,12 By definition, techniques other than laser corneal refractive surgical procedures should be taken into consideration for www.corneajrnl.com |
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the correction of residual refractive error in keratoconic patients post crosslinking.6 We present an interventional case series of implantation of posterior chamber toric phakic ICLs in keratoconic patients with myopia and/or astigmatism who already underwent corneal collagen crosslinking to assess the safety, predictability, and efficacy of this modality of treatment.
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and incorporates a forward vault to minimize contact of the Visian ICL with the central anterior capsule. The Visian ICL is intended to be placed entirely within the posterior chamber directly behind the iris and in front of the anterior capsule of the human crystalline lens, and when correctly positioned, the lens functions as a refractive element to optically reduce moderate-to-high myopia.
MATERIALS AND METHODS The approval of the ethical committee of the University of Alexandria was obtained before starting our study. All patients signed an informed consent after receiving a detailed description of the nature of this modality of treatment. In this prospective interventional case series study, we have evaluated the results of posterior chamber Toric ICL (TICL) implantation in 16 eyes of keratoconic patients who underwent corneal collagen crosslinking and showed refractive stability for at least 12 months. Stable refraction was determined by 2 subjective refractions within 60.50 diopters (D) of spherical equivalent 3 months apart. The inclusion criteria were that patients had a normal systemic history and normal physical examination results, absence of any history or physical signs of ocular disease with the exception of keratoconus and myopia, age between 21 and 35 years, best spectacle-corrected visual acuity (CDVA) of 0.4 (20/50) or better in the eye to be treated, stable refraction for at least 12 months after corneal collagen crosslinking, clear central cornea, normal anterior segment with an anterior chamber depth at least 3.00 mm excluding the corneal thickness, and intraocular pressure (IOP) ,20 mm Hg. The Food and Drug Administration recommendations for the preoperative endothelial cell count were followed in relation to the age of the patient and the anterior chamber depth. Patients could undergo the crosslinking procedure only if they had progressive keratoconus, a clear nonscared cornea, and a corneal thickness of at least 400 mm without the epithelium at the thinnest location as documented by the Pentacam-HR. Progressive keratoconus was diagnosed based on the following: (1) increase in the steepest K readings of at least 1.00 D in 1 year as documented by corneal topography and/or the Pentacam-HR; (2) deterioration of the bestcorrected visual acuity; (3) need for new contact lens fitting more than once in 2 years. The preoperative assessment of the patients included CDVA; manifest and cycloplegic refraction; anterior chamber depth measurement and corneal curvature information (K readings) using an IOL Master (Carl Zeiss, Jena, Germany); white-to-white measurement using a Caliper (Moria, Anthony, France) and an IOL Master; and an assessment of anterior, posterior corneal surfaces, and anterior chamber using a Scheimpflug camera system (Pentacam, Oculus, Inc). The ICL power was calculated using the software ICL Power choice of STAAR Surgical. The STAAR Surgical Visian ICL is an intraocular implant manufactured from a proprietary hydroxyethyl methacrylate/porcine collagen–based biocompatible polymer material. The Visian ICL contains a UV absorber made from a UV-absorbing material. The Visian ICL features a platehaptic design with a central convex/concave optical zone
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Surgical Procedures All the eyes included in this study had progressive keratoconus and underwent corneal collagen crosslinking performed by 1 surgeon (M.E.-K.) using the standard epithelial-off technique and 0.1% Ricrolin (Sooft, Italy; vitamin B2—riboflavin-5-phosphate 0.5% with the 20% T-Dextran Solution) for 15 to 20 minutes and were then exposed to UV-A irradiation at 3 mW/cm2 for 30 minutes. The epithelium was removed using the Amoils brush (Innovative Excimer Solutions Inc, Toronto, ON). All TICL implant surgeries were performed under general anesthesia by the same surgeon (M.S.S) at least 12 months after the crosslinking. Two hours before the surgery, a cycloplegic solution (cyclopentolate hydrochloride 10 mg/mL; Alcon Lab, Inc, Fort Worth, TX) and phenylephrine ophthalmic solution 2.5% (Alcon Lab, Inc, Fort Worth, TX) were instilled every 15 minutes. The anterior chamber was filled with sodium hyaluronate 1%, which was completely removed at the end of the surgery. Insertion was performed through a 3-mm clear corneal temporal tunnel incision. The pupil was constricted using Miochol-E (acetylcholine chloride intraocular solution) 1:100 with Electrolyte Diluent (Novartis, Switzerland). Surgical iridectomy after pupil constriction was achieved using a vitrectomy cutter. Postoperatively, gatifloxacin ophthalmic solution and dexamethasone drops were prescribed 4 times daily for 10 days. In cases of bilateral implantation, the second eye was operated within the first postoperative week of the fellow eye. The follow-up was done up to 3 years postoperatively for all the patients; uncorrected visual acuity (UDVA), CDVA, slitlamp examination, manifest and cycloplegic refraction, ICL vaulting, and IOP were evaluated and reported at every follow-up visit. There were no dropped-out visits in the entire follow-up period. Data analysis was performed using SPSS for Windows version 16.01 (SPSS Inc, Chicago, IL). The normality of data distribution was checked by the Kolmogorov–Smirnov test. Means were compared using a Wilcoxon signed-rank test and analysis of variance with repeated measures with the Bonferroni adjustment, and differences were considered to be statistically significant when the P value was ,0.05. Type 2 error was also calculated, and values ,0.1 were considered insignificant.
RESULTS This study evaluated 16 eyes of 11 keratoconic patients (8 females and 3 males) who underwent TICL implantation at least 12 months after having their corneal collagen crosslinked and demonstrated stable refraction during this period; Ó 2014 Lippincott Williams & Wilkins
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the mean age of the patients studied was 25.5 6 4 years (range, 20–35 years). Five patients underwent bilateral implantation, whereas 6 patients underwent unilateral intervention (11 female eyes and 5 male eyes).
Visual Acuity Table 1 shows the different periods of the CDVA in the patients studied; as noticed, the mean CDVA improved from 0.56 before crosslinking to .0.8 after 1 week of the ICL implantation, and this improvement was maintained throughout the follow-up period. The beta type 2 error was 0.0987. Table 2 shows the difference between the CDVA before the surgery and the postoperative UDVA demonstrating a significant improvement in the visual acuity as the mean for the preoperative CDVA was 0.63 6 0.14 and the mean of the postoperative UDVA was about 0.8 at 1 week and maintained throughout the rest of the follow-up or even got slightly better. The beta type 2 error was 0.0842.
Refraction Considering the sphere, the preoperative mean was about 26.00 6 4.00 D, which improved to almost undetectable levels postoperatively. Preoperatively, the mean cylinder was about 25:00 6 1.50 D, and this improved to 0.0 D postoperatively; the spherical equivalent preoperatively was 28.50 6 4.00 D, and this improved postoperatively to less than 20.25 D. The beta type 2 error was 0.0835. In this study, we used the preoperative manifest refraction to calculate the TICL power. The beta type 2 error was 0.0762.
Vaulting of the TICL
The mean values were 539.13 6 161.94 mm, 524.88 6 151.61 mm, 509.12 6 121.7 mm, 508.75 6 132.4 mm, 508.90 6 111.6 mm, and 507.12 6 117.3 mm for the
1-week; 1-, 3-, 6-, 12-month; and 3-year postoperative periods of the follow-up, respectively.
Intraocular Pressure
The mean values were 12.0 6 1.03 mm Hg, 14.38 6 2.45 mm Hg, 13.0 6 1.51 mm Hg, 12.19 6 1.33 mm Hg, 11.94 6 1.12 mm Hg, and 11.94 6 1.12 mm Hg for the 1-week; 1-, 3-, 6-, 12-month; and 3-year postoperative periods of the follow-up, respectively.
Endothelial Cell Count The mean preoperative endothelial cell count was 2850 cells per square millimeter; after 1 year, it was 2705 cells per square millimeter (25.08% cell loss). After 2 years, it was 2650 cells per square millimeter (27.01% cell loss), and after 3 years, it was 2594 cells per square millimeter (28.89% cell loss). No complications occurred during the surgical procedures. No eye needed explantation or repositioning of the TICL. Decentration of the TICL optic was not observed, and no case of pupillary block was detected.
DISCUSSION Refractive surgical correction of ametropia in patients with keratoconus remains challenging. Progressive thinning and subsequent anterior bulging of the cornea can lead to severe astigmatism that is often accompanied by myopia and central scarring, resulting in mild-to-marked impairment in the quantity and quality of vision.13,14 Spectacles and contact lenses are the usual optical treatment options in the early stages of keratoconus.15 In more advanced cases with severe corneal astigmatism and stromal opacity, patients may not tolerate contact lenses or there may be no improvement in visual acuity on using contact lenses. In these cases, a penetrating keratoplasty (PKP) or a deep anterior lamellar keratoplasty is necessary to restore visual function.16
TABLE 1. Comparison Between Different Periods of CDVA for TICL Implantation After Corneal Crosslinking for Keratoconus CDVA Range Mean 6 SD Median F (p) Mean difference Mean difference Mean difference Mean difference Mean difference Mean difference
Before Crosslinking
Before ICL
After 7 Days
After 1 Month
After 6 Months
After 1 Year
After 3 Years
0.40–0.80 0.56 6 0.13 0.60
0.40–0.80 0.63 6 0.14 0.60
0.60–1.20 0.82 6 0.16 0.85
0.60–1.20 0.89 6 0.17 0.90
0.60–1.20 0.89 6 0.17 0.90
0.60–1.20 0.89 6 0.17 0.90
0.063* (0.002)
0.256* (,0.001) 0.194* (0.002)
0.60–1.20 0.87 6 0.15 0.85 69.362* (,0.001) 0.306* (0.028) 0.244* (,0.001) 0.050* (0.032)
0.325* (,0.001) 0.263* (,0.001) 0.069 (0.139) 0.019 (1.000)
0.325* (,0.001) 0.263* (,0.001) 0.069 (0.139) 0.019 (1.000) 0.0 (—)
0.325* (,0.001) 0.263* (,0.001) 0.069 (0.139) 0.019 (1.000) 0.0 (—) 0.0 (—)
(p1) (p2) (p3) (p4) (p5) (p6)
*Statistically significant at P # 0.05. p1, Bonferroni-adjusted P value for comparison between pre crosslinking with each other period; p2, Bonferroni-adjusted P value for comparison between pre-ICL with each other period; p3, Bonferroni adjusted P value for comparison between after 7 days with each other period; p4, Bonferroni adjusted P value for comparison between after I months with each other period; p5, Bonferroni adjusted P value for comparison between after 6 months with each other period; p6, Bonferroni adjusted P value for comparison between after 1 year and after 3 years.
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TABLE 2. Comparison Between Different Periods of UCVA for TICL Implantation After Corneal Crosslinking for Keratoconus UCVA Range Mean 6 SD Median F (p) Mean difference Mean difference Mean difference Mean difference Mean difference
CDVA Before ICL
After 7 Days
After 1 Month
After 6 Months
After 1 Year
After 3 Years
0.40–0.80 0.63 6 0.14 0.60
0.60–1.20 0.79 6 0.16 0.80
0.60–1.20 0.83 6 0.16 0.80 43.022* (,0.001) 0.206* (,0.001) 0.038 (0.135)
0.60–1.20 0.85 6 0.15 0.80
0.60–1.20 0.88 6 0.18 0.85
0.60–1.20 0.88 6 0.18 0.85
0.250* (,0.001) 0.081* (0.042) 0.044 (0.210)
0.250* (,0.001) 0.081* (0.042) 0.044 (0.210) 0.0 (2)
0.250* (,0.001) 0.081* (0.042) 0.044 (0.210) 0.0 (2) 0.0 (2)
(p1) (p2) (p3) (p4) (p5)
0.169* (0.002)
*Statistically significant at P # 0.05. p1, Bonferroni adjusted P value for comparison between pre-ICL with each other period; p2, Bonferroni adjusted P value for comparison between after 7 days with each other period; p3, Bonferroni adjusted P value for comparison between after 1 month with each other period; p4, Bonferroni adjusted P value for comparison between after 6 month with each other period; p5, Bonferroni adjusted P value for comparison between after 1 year and after 3 years; UCVA, uncorrected distant visual acuity.
Collagen crosslinking using riboflavin and UV light was recently introduced6,17; however, crosslinking alone stabilizes and stiffens the cornea by inducing more corneal collagen crosslinks of keratoconus, and the remaining refractive errors will still need to be corrected. After thoroughly searching the literature, we found only 2 published articles18,19 that were similar to our study. The first was published by Kymionis et al18 who described a case report of TICL implantation performed after corneal crosslinking. The second article was published by Fadlallah et al19 and included 16 eyes with previous corneal crosslinking for progressive keratoconus and then an implantation of TICL with an interval of 6 months and a follow-up period for only 6 months. Therefore, we believe that our study is the first reported work of its kind to include this number of studied eyes, and having a relatively long follow-up duration of 3 years. In this prospective nonrandomized clinical interventional study of 16 eyes, we aimed to determine whether the implantation of a TICL in corneas that had been crosslinked and showed refractive stability for at least 12 months is safe, predictable, and effective in correcting different ranges of myopia and astigmatism in eyes with early-stage keratoconus. We obtained very satisfactory refractive outcomes in predictability with all the eyes being within 0.5 D of the intended spherical equivalent; the mean spherical equivalent was ,0.25 D 3 years after the surgery. In addition, the astigmatism decreased significantly to nearly clinically insignificant values. Regarding visual outcomes, the efficacy was good with .81% of the eyes having a postoperative UDVA of $0.8 and all the operated eyes maintaining a CDVA or gaining multiple lines of CDVA. The results are similar to those obtained by Fadlallah et al,19 but our study had a longer follow-up duration (3 years). The efficacy and predictability of posterior chamber phakic toric IOLs in the treatment of myopia with low-to-high astigmatism in keratoconic eyes are supported by recent reports.11,20–22 There are 2 studies of TICL implantation in eyes with keratoconus that had not undergone crosslinking.23,24 The
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first study was performed by Kamiya et al23 on a very small sample (2 eyes of 2 patients with stable keratoconus). The other study was performed by Alfonso et al,24 who obtained very satisfactory refractive outcomes in predictability with all the eyes being within 1.00 D of the intended spherical equivalent; the mean spherical equivalent was ,0.25 D 12 months after surgery. In addition, astigmatism decreased significantly to nearly clinically insignificant values. Regarding visual outcomes, the efficacy was good with .60% of the eyes having a postoperative UDVA of $0.8 and 97% of the operated eyes maintaining a CDVA or gaining multiple lines of the CDVA. The results are consistent with our results, but it is difficult to directly compare with this study because of the difference in the number of cases and the crosslinking not being performed before the TICL implantation. The most commonly reported postoperative complications of the ICL implantation are anterior subcapsular cataract25–27 and increased IOP.28,29 Sanders30 reported that anterior subcapsular opacities and cataract occurred 5 years after surgery in the Food and Drug Administration trial. Although approximately 6% to 7% of eyes developed anterior subcapsular opacities $7 years after phakic IOL implantation, the opacity progressed to a clinically significant cataract in only 1% to 2% during the same period, with most cases being observed in older patients and in eyes with very high myopia. There were no cases of chronic increased postoperative IOP or anterior subcapsular cataract in our study. Another concern is the degree of vaulting of the implanted ICL and how it changes over time; a study performed by Kojima et al31 1 year after ICL implantation in 36 eyes showed that the mean vault was 0.53 6 0.25 mm. A result consistent with the results in our study, which showed a mean vault of 0.509 6 0.141 mm at 1 year postoperatively. We also demonstrated that a high vault gradually decreases over time. The reason for the decrease in the initial vaulting measures especially from the 1-week to 1-month period of the postoperative follow-up may be related to the residual viscoelastic material that was present between the ICL and the crystalline lens, although meticulous irrigation/ Ó 2014 Lippincott Williams & Wilkins
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aspiration was performed. A complete irrigation is often difficult because of the presence of a narrow space between the crystalline lens and the ICL. No complications occurred during the surgical procedures. No eye needed explantation or repositioning of the TICL. Decentration of the TICL optic was not observed, and no case of pupillary block was detected. It is preferable that TICL implantation not be performed until refraction and keratometry are stable after corneal collagen crosslinking. We suggest the following indications for TICL implantation in keratoconus: CDVA $20/50, clear central cornea, and stable refraction for at least 12 months after crosslinking. If these criteria are not met, a PKP would probably provide better visual outcomes. Thus, TICL implantation should not be considered a true alternative to PKP but rather an alternative treatment in cases of early stages of keratoconus with a relatively low irregular regular astigmatism. All intraocular procedures entail some degree of endothelial cell loss, and insertion of a phakic IOL induces between 2.1% and 7.6%.32 Postoperative endothelial loss is also an important issue. For the ICL, the 1-year endothelial cell loss rate was 5.17% in 1 study,33 and, in another, a cumulative decrease of 7.7% was seen in the endothelial cell density over 5 years.34 The reason for the discrepancy is possibly because of chronic low-grade inflammation.35 In conclusion, we found that correction of spherical and cylindrical refractive errors in keratoconic eyes by TICL implantation up to 3 years after crosslinking seems to have significantly better outcomes, particularly in the astigmatic component of refraction. The significant visual improvement after this procedure could be attributed to 2 factors; the effect of the crosslinking on flattening/ regularizing the cornea and the correcting effect of the TICL on a plane near the nodal point of the line of sight. We recommend meticulous repeated refraction of these eyes to obtain the subjective refraction and to calculate the ICL power using it to target postoperative emmetropia. Nevertheless, long-term randomized comparative prospective studies with large cohorts are needed to assess the stability and potential complications of the procedure and the possible combination with other treatments in cases of keratoconus progression and refraction change. REFERENCES 1. Wolf FR, Hoyer A, Spoerl E, et al. Collagen crosslinking with riboflavin and ultraviolet-A light in keratoconus: long-term results. J Cataract Refract Surg. 2008;34:796–801. 2. Kymes SM, Walline JJ, Zadnik K, et al. Quality of life in keratoconus. Am J Ophthalmol. 2004;138:527–535. 3. Maeno A, Naor J, Lee HM. Three decades of corneal transplantation: indications and patient characteristics. Cornea. 2000;19:7–11. 4. Caporossi A, Baiocchi S, Mazzotta C. Parasurgical therapy for keratoconus by riboflavin–ultraviolet type A rays induced cross-linking of corneal collagen: preliminary refractive results in an Italian study. J Cataract Refract Surg. 2006;32:837–845. 5. Meek KM, Tuft SJ, Huang Y. Changes in collagen orientation and distribution in keratoconus corneas. Invest Ophthalmol Vis Sci. 2005;46: 1948–1956.
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6. Wollensak G. Crosslinking treatment of progressive keratoconus: new hope. Curr Opin Ophthalmol. 2006;17:356–360. 7. Spoerl E, Wollensak G, Seiler T. Increased resistance of crosslinked cornea against enzymatic digestion. Curr Eye Res. 2004;29:35–40. 8. Spöerl E, Schreiber J, Hellmund K. Studies on the stabilization of the cornea in rabbits [in German]. Ophthalmologe. 2000;97: 203–206. 9. Kohlhaas M, Spoerl E, Schilde T. Biomechanical evidence of the distribution of cross-links in corneas treated with riboflavin and ultraviolet A light. J Cataract Refract Surg. 2006;32:279–283. 10. Coskunseven E, Onder M, Kymionis GD. Combined intacs and posterior chamber toric implantable collamer lens implantation for keratoconic patients with extreme myopia. Am J Ophthalmol. 2007;144: 387–389. 11. Sanders DR, Shneider D, Martin R, et al. Toric implantable collamer lens for moderate to high myopic astigmatism. Ophthalmology. 2007; 114:54–61. 12. Alfonso JF, Palacios A, Montés-Micó R. Myopic phakic STAAR collamer posterior chamber intraocular lenses for keratoconus. J Refract Surg. 2008;24:867–874. 13. Davis LJ, Schechtman KB, Wilson BS, et al. Longitudinal changes in visual acuity in keratoconus. Invest Ophthalmol Vis Sci. 2006;47: 489–500. 14. Zadnik K, Barr JT, Edrington TB, et al. Corneal scarring and vision in keratoconus: a baseline report from the collaborative longitudinal evaluation of keratoconus (CLEK) study; the CLEK study group. Cornea. 2000;19:804–812. 15. Mahadevan R, Arumugam AO, Arunachalam V, et al. Keratoconus— a review from a tertiary eye-care center. J Optom. 2009;2:166–172. 16. Gordon MO, Steger-May K, Szczotka-Flynn L, et al. Baseline factors predictive of incident penetrating keratoplasty in keratoconus. Am J Ophthalmol. 2006;142:923–930. 17. Wollensak G, Spoerl E, Seiler T. Riboflavin/ultraviolet-a-induced collagen crosslinking for the treatment of keratoconus. Am J Ophthalmol. 2003;135:620–627. 18. Kymionis GD, Grentzelos MA, Karavitaki AE, et al. Combined corneal collagen cross-linking and posterior chamber toric implantable collamer lens implantation for keratoconus. Ophthalmic Surg Lasers Imaging. 2011;42:e22–e25. 19. Fadlallah A, Dirani A, El Rami H, et al. Safety and visual outcome of Visian toric ICL implantation after corneal collagen cross-linking for keratoconus. J Refract Surg. 2013;29:84–89. 20. Kamiya K, Shimizu K, Igarashi A, et al. Comparison of collamertoric [corrected] contact lens implantation and wavefront-guided laser in situ keratomileusis for high myopic astigmatism. J Cataract Refract Surg. 2008;34:1687–1693; erratum, 2011. 21. Sanders DR, Sanders ML. Comparison of the toric implantable collamer lens and custom ablation LASIK for myopic astigmatism. J Refract Surg. 2008;24:773–778. 22. Alfonso JF, Fernández-Vega L, Fernandes P, et al. Collagen copolymer toric posterior chamber phakic intraocular lens for myopic astigmatism: one-year follow-up. J Cataract Refract Surg. 2010;36:568–576. 23. Kamiya K, Shimizu K, Ando W, et al. Phakictoric implantable collamer lens implantation for the correction of high myopic astigmatism in eyes with keratoconus. J Refract Surg. 2008;24:840–842. 24. Alfonso JF, Baamonde B, Madrid-Costa D, et al. Toric phakic intraocular collamer posterior chamber lenses to correct high degrees of myopic astigmatism. J Cataract Refract Surg. 2010;36:577–586. 25. Gonvers M, Bornet C, Othenin-Girard P. Implantable contact lens for moderate to high myopia; relationship of vaulting to cataract formation. J Cataract Refract Surg. 2003;29:918–924. 26. Sanders DR, Vukich JA. Incidence of lens opacities and clinically significant cataracts with the implantable contact lens: comparison of two lens designs; the ICL in treatment of myopia (ITM) study group. J Refract Surg. 2002;18:673–682. 27. Jiménez-Alfaro I, Benítez del Castillo JM, García-Feijoó J, et al. Safety of posterior chamber phakic intraocular lenses for the correction of high myopia; anterior segment changes after posterior chamber phakic intraocular lens implantation. Ophthalmology. 2001;108:90–99; discussion by SM MacRay, 99.
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28. Chung TY, Park SC, Lee MO, et al. Changes in iridocorneal angle structure and trabecular pigmentation with STAAR implantable collamer lens during 2 years. J Refract Surg. 2009;25:251–258. 29. Chun YS, Park IK, Lee HI, et al. Iris and trabecular meshwork pigment changes after posterior chamber phakic intraocular lens implantation. J Cataract Refract Surg. 2006;32:1452–1458. 30. Sanders DR. Anterior subcapsular opacities and cataracts 5 years after surgery in the visian implantable collamer lens FDA trial. J Refract Surg. 2008;24:566–570. 31. Kojima T, Maeda M, Yoshida Y, et al. Posterior chamber phakic implantable collamer lens: changes in vault during 1 year. J Refract Surg. 2010;26:327–332.
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32. Lovisolo CF, Reinstein DZ. Phakic intraocular lenses. Surv Ophthalmol. 2005;50:549–587. 33. Jiminez-Alfaro I, Benitez del Castillo JM, Garcia-Feijoo J, et al. Safety of posterior chamber phakic intraocular lenses for the correction of high myopia: anterior segment changes after posterior chamber phakic intraocular lens implantation. Ophthalmology. 2001;108: 90–99. 34. Alfonso JF, Baamonde B, Fernández-Vega L, et al. Posterior chamber collagen copolymer phakic intraocular lenses to correct myopia: five-year follow up. J Cataract Refract Surg. 2011;37:873–880. 35. Bozkurt E, Yazici AT, Yildirim Y, et al. Long-term follow-up of firstgeneration posterior chamber phakic intraocular lens. J Cataract Refract Surg. 2010;36:1602–1604.
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Evaluation of a Toric Implantable Collamer Lens After Corneal Collagen Crosslinking in Treatment of Early-Stage Keratoconus: 3-Year Follow-up Mohamed Shafik Shaheen, MD, PhD,* Mohamed El-Kateb, MD, PhD,* Mohamed A. El-Samadouny, MD, PhD,* and Hussam Zaghloul, MD†
Purpose: The aim of this study was to assess the predictability, efficacy, safety, and stability in patients who received a toric implantable collamer lens (TICL) after collagen crosslinking in early-stage keratoconus.
Methods: This prospective interventional case series study was conducted at the Alexandria Main University hospitals, University of Alexandria, Egypt. Sixteen eyes underwent implantation of a TICL (STAAR Surgical Inc) after crosslinking. The mean spherical refraction was 25.98 6 4.39 diopters (D) (range, 20.50 to 214.50 D), and the mean cylinder was 24.91 6 1.51 D (range, 22.50 to 27.75 D). Uncorrected distance visual acuity (UDVA), manifest and cycloplegic refraction, corrected distance visual acuity (CDVA), vault, intraocular pressure, and endothelial cell count (using specular microscopy) were evaluated during a 3-year follow-up. Results: The mean Snellen decimal CDVA improved from 0.56 6
0.13 (range, 0.40–0.80) preoperatively to 0.89 6 0.17 (range, 0.60– 1.20) at 3 years of the follow-up (P , 0.0001). The mean UDVA also improved significantly from 0.63 6 0.14 before ICL implantation to 0.88 6 0.18 after 3 years of the follow-up (P , 0.001). At 3 years, the mean spherical and cylindrical manifest refractions were 0.00 6 0.18 D and 20.05 6 0.14 D, respectively. At the end of the follow-up, the vault was 509.75 6 141.47 mm (range, 320–900) and the intraocular pressure was 11.94 6 1.12 mm Hg. No complications occurred during the surgical procedures. No eye needed explantation or repositioning of the TICL. The endothelial cell count loss after 3 years was 28.98%.
Conclusions: Correction of spherical and cylindrical refractive errors in keratoconic eyes by TICL implantation 12 months after crosslinking gave significantly promising outcomes, particularly in the astigmatic component of refraction. Key Words: keratoconus, crosslinking, toric implantable collamer lens (Cornea 2014;33:475–480) Received for publication December 6, 2013; revision received January 13, 2014; accepted January 14, 2014. Published online ahead of print March 11, 2014. From the *Department of Ophthalmology, University of Alexandria, Alexandria, Egypt; and †Armed Forces Hospitals, Alexandria, Egypt. The authors have no funding or conflicts of interest to disclose. Reprints: Mohamed S. Shaheen, University of Alexandria, PO Box 27, Ibrahimia, Alexandria 21321, Egypt (e-mail: m.shafi[email protected]). Copyright © 2014 by Lippincott Williams & Wilkins
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K
eratoconus is a corneal degeneration characterized by bilateral conical protrusion and corneal thinning.1 The average age of onset of keratoconus is the twenties.2 The course of the disease varies from slight irregular astigmatism to severe visual impairment because of increasing protrusion and subepithelial scarring.3 Because of the young age of the patients, keratoconus often has a significant negative effect on the quality of life.2 The results of currently available treatment options are not encouraging because the treatments do not stop the progression of keratoconus. Thus, because of its progressive nature, keratoconus was the most frequent reason for keratoplasty to be performed in the past 3 decades.4 Keratoconus leads to biomechanical alterations, and its specific cause is not known.5,6 The biomechanical characteristics of the cornea result from the collagen scaffold and collagen compound and their bonding with the collagen fibrils. The 3-dimensional configuration of the collagen lamella fundamentally codetermines the resistance of the cornea.7,8 Biochemical and immunohistochemical studies of matrix proteoglycans show that differences exist between normal and keratoconic corneas.5 Enzymatic alterations with an increased expression of lysosomal and proteolytic enzymes,5,7 decreased concentration of protease inhibitors,5,7 decreased thickness,5 and modified configuration of the stromal collagen lamella7 have been observed. A photooxidative collagen crosslinking technique using riboflavin and ultraviolet (UV)-A light was developed to counteract the progressive corneal thinning and thus the progression of keratoconus. By crosslinking, additional covalent binding between collagen molecules can be achieved, which stabilizes the collagen scaffold and changes several tissue properties.4 An increase in the corneal stiffness and enhanced resistance against proteolytic enzymes caused by the riboflavin and UV-A light was shown in human eyes.9 The crosslinking effect is not distributed homogenously over the corneal depth. The stiffening effect is concentrated in the anterior 200 to 300 mm of the cornea because of the high absorption of UV light in this area.10 The Implantable Collamer Lens (ICL; STAAR Surgical, Nidau, Switzerland) is a posterior chamber phakic intraocular lens, which has been reported not only for its superiority in postoperative visual performance but also for its safety and effectiveness in the correction of moderate to high myopic astigmatism.11,12 By definition, techniques other than laser corneal refractive surgical procedures should be taken into consideration for www.corneajrnl.com |
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the correction of residual refractive error in keratoconic patients post crosslinking.6 We present an interventional case series of implantation of posterior chamber toric phakic ICLs in keratoconic patients with myopia and/or astigmatism who already underwent corneal collagen crosslinking to assess the safety, predictability, and efficacy of this modality of treatment.
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and incorporates a forward vault to minimize contact of the Visian ICL with the central anterior capsule. The Visian ICL is intended to be placed entirely within the posterior chamber directly behind the iris and in front of the anterior capsule of the human crystalline lens, and when correctly positioned, the lens functions as a refractive element to optically reduce moderate-to-high myopia.
MATERIALS AND METHODS The approval of the ethical committee of the University of Alexandria was obtained before starting our study. All patients signed an informed consent after receiving a detailed description of the nature of this modality of treatment. In this prospective interventional case series study, we have evaluated the results of posterior chamber Toric ICL (TICL) implantation in 16 eyes of keratoconic patients who underwent corneal collagen crosslinking and showed refractive stability for at least 12 months. Stable refraction was determined by 2 subjective refractions within 60.50 diopters (D) of spherical equivalent 3 months apart. The inclusion criteria were that patients had a normal systemic history and normal physical examination results, absence of any history or physical signs of ocular disease with the exception of keratoconus and myopia, age between 21 and 35 years, best spectacle-corrected visual acuity (CDVA) of 0.4 (20/50) or better in the eye to be treated, stable refraction for at least 12 months after corneal collagen crosslinking, clear central cornea, normal anterior segment with an anterior chamber depth at least 3.00 mm excluding the corneal thickness, and intraocular pressure (IOP) ,20 mm Hg. The Food and Drug Administration recommendations for the preoperative endothelial cell count were followed in relation to the age of the patient and the anterior chamber depth. Patients could undergo the crosslinking procedure only if they had progressive keratoconus, a clear nonscared cornea, and a corneal thickness of at least 400 mm without the epithelium at the thinnest location as documented by the Pentacam-HR. Progressive keratoconus was diagnosed based on the following: (1) increase in the steepest K readings of at least 1.00 D in 1 year as documented by corneal topography and/or the Pentacam-HR; (2) deterioration of the bestcorrected visual acuity; (3) need for new contact lens fitting more than once in 2 years. The preoperative assessment of the patients included CDVA; manifest and cycloplegic refraction; anterior chamber depth measurement and corneal curvature information (K readings) using an IOL Master (Carl Zeiss, Jena, Germany); white-to-white measurement using a Caliper (Moria, Anthony, France) and an IOL Master; and an assessment of anterior, posterior corneal surfaces, and anterior chamber using a Scheimpflug camera system (Pentacam, Oculus, Inc). The ICL power was calculated using the software ICL Power choice of STAAR Surgical. The STAAR Surgical Visian ICL is an intraocular implant manufactured from a proprietary hydroxyethyl methacrylate/porcine collagen–based biocompatible polymer material. The Visian ICL contains a UV absorber made from a UV-absorbing material. The Visian ICL features a platehaptic design with a central convex/concave optical zone
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Surgical Procedures All the eyes included in this study had progressive keratoconus and underwent corneal collagen crosslinking performed by 1 surgeon (M.E.-K.) using the standard epithelial-off technique and 0.1% Ricrolin (Sooft, Italy; vitamin B2—riboflavin-5-phosphate 0.5% with the 20% T-Dextran Solution) for 15 to 20 minutes and were then exposed to UV-A irradiation at 3 mW/cm2 for 30 minutes. The epithelium was removed using the Amoils brush (Innovative Excimer Solutions Inc, Toronto, ON). All TICL implant surgeries were performed under general anesthesia by the same surgeon (M.S.S) at least 12 months after the crosslinking. Two hours before the surgery, a cycloplegic solution (cyclopentolate hydrochloride 10 mg/mL; Alcon Lab, Inc, Fort Worth, TX) and phenylephrine ophthalmic solution 2.5% (Alcon Lab, Inc, Fort Worth, TX) were instilled every 15 minutes. The anterior chamber was filled with sodium hyaluronate 1%, which was completely removed at the end of the surgery. Insertion was performed through a 3-mm clear corneal temporal tunnel incision. The pupil was constricted using Miochol-E (acetylcholine chloride intraocular solution) 1:100 with Electrolyte Diluent (Novartis, Switzerland). Surgical iridectomy after pupil constriction was achieved using a vitrectomy cutter. Postoperatively, gatifloxacin ophthalmic solution and dexamethasone drops were prescribed 4 times daily for 10 days. In cases of bilateral implantation, the second eye was operated within the first postoperative week of the fellow eye. The follow-up was done up to 3 years postoperatively for all the patients; uncorrected visual acuity (UDVA), CDVA, slitlamp examination, manifest and cycloplegic refraction, ICL vaulting, and IOP were evaluated and reported at every follow-up visit. There were no dropped-out visits in the entire follow-up period. Data analysis was performed using SPSS for Windows version 16.01 (SPSS Inc, Chicago, IL). The normality of data distribution was checked by the Kolmogorov–Smirnov test. Means were compared using a Wilcoxon signed-rank test and analysis of variance with repeated measures with the Bonferroni adjustment, and differences were considered to be statistically significant when the P value was ,0.05. Type 2 error was also calculated, and values ,0.1 were considered insignificant.
RESULTS This study evaluated 16 eyes of 11 keratoconic patients (8 females and 3 males) who underwent TICL implantation at least 12 months after having their corneal collagen crosslinked and demonstrated stable refraction during this period; Ó 2014 Lippincott Williams & Wilkins
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the mean age of the patients studied was 25.5 6 4 years (range, 20–35 years). Five patients underwent bilateral implantation, whereas 6 patients underwent unilateral intervention (11 female eyes and 5 male eyes).
Visual Acuity Table 1 shows the different periods of the CDVA in the patients studied; as noticed, the mean CDVA improved from 0.56 before crosslinking to .0.8 after 1 week of the ICL implantation, and this improvement was maintained throughout the follow-up period. The beta type 2 error was 0.0987. Table 2 shows the difference between the CDVA before the surgery and the postoperative UDVA demonstrating a significant improvement in the visual acuity as the mean for the preoperative CDVA was 0.63 6 0.14 and the mean of the postoperative UDVA was about 0.8 at 1 week and maintained throughout the rest of the follow-up or even got slightly better. The beta type 2 error was 0.0842.
Refraction Considering the sphere, the preoperative mean was about 26.00 6 4.00 D, which improved to almost undetectable levels postoperatively. Preoperatively, the mean cylinder was about 25:00 6 1.50 D, and this improved to 0.0 D postoperatively; the spherical equivalent preoperatively was 28.50 6 4.00 D, and this improved postoperatively to less than 20.25 D. The beta type 2 error was 0.0835. In this study, we used the preoperative manifest refraction to calculate the TICL power. The beta type 2 error was 0.0762.
Vaulting of the TICL
The mean values were 539.13 6 161.94 mm, 524.88 6 151.61 mm, 509.12 6 121.7 mm, 508.75 6 132.4 mm, 508.90 6 111.6 mm, and 507.12 6 117.3 mm for the
1-week; 1-, 3-, 6-, 12-month; and 3-year postoperative periods of the follow-up, respectively.
Intraocular Pressure
The mean values were 12.0 6 1.03 mm Hg, 14.38 6 2.45 mm Hg, 13.0 6 1.51 mm Hg, 12.19 6 1.33 mm Hg, 11.94 6 1.12 mm Hg, and 11.94 6 1.12 mm Hg for the 1-week; 1-, 3-, 6-, 12-month; and 3-year postoperative periods of the follow-up, respectively.
Endothelial Cell Count The mean preoperative endothelial cell count was 2850 cells per square millimeter; after 1 year, it was 2705 cells per square millimeter (25.08% cell loss). After 2 years, it was 2650 cells per square millimeter (27.01% cell loss), and after 3 years, it was 2594 cells per square millimeter (28.89% cell loss). No complications occurred during the surgical procedures. No eye needed explantation or repositioning of the TICL. Decentration of the TICL optic was not observed, and no case of pupillary block was detected.
DISCUSSION Refractive surgical correction of ametropia in patients with keratoconus remains challenging. Progressive thinning and subsequent anterior bulging of the cornea can lead to severe astigmatism that is often accompanied by myopia and central scarring, resulting in mild-to-marked impairment in the quantity and quality of vision.13,14 Spectacles and contact lenses are the usual optical treatment options in the early stages of keratoconus.15 In more advanced cases with severe corneal astigmatism and stromal opacity, patients may not tolerate contact lenses or there may be no improvement in visual acuity on using contact lenses. In these cases, a penetrating keratoplasty (PKP) or a deep anterior lamellar keratoplasty is necessary to restore visual function.16
TABLE 1. Comparison Between Different Periods of CDVA for TICL Implantation After Corneal Crosslinking for Keratoconus CDVA Range Mean 6 SD Median F (p) Mean difference Mean difference Mean difference Mean difference Mean difference Mean difference
Before Crosslinking
Before ICL
After 7 Days
After 1 Month
After 6 Months
After 1 Year
After 3 Years
0.40–0.80 0.56 6 0.13 0.60
0.40–0.80 0.63 6 0.14 0.60
0.60–1.20 0.82 6 0.16 0.85
0.60–1.20 0.89 6 0.17 0.90
0.60–1.20 0.89 6 0.17 0.90
0.60–1.20 0.89 6 0.17 0.90
0.063* (0.002)
0.256* (,0.001) 0.194* (0.002)
0.60–1.20 0.87 6 0.15 0.85 69.362* (,0.001) 0.306* (0.028) 0.244* (,0.001) 0.050* (0.032)
0.325* (,0.001) 0.263* (,0.001) 0.069 (0.139) 0.019 (1.000)
0.325* (,0.001) 0.263* (,0.001) 0.069 (0.139) 0.019 (1.000) 0.0 (—)
0.325* (,0.001) 0.263* (,0.001) 0.069 (0.139) 0.019 (1.000) 0.0 (—) 0.0 (—)
(p1) (p2) (p3) (p4) (p5) (p6)
*Statistically significant at P # 0.05. p1, Bonferroni-adjusted P value for comparison between pre crosslinking with each other period; p2, Bonferroni-adjusted P value for comparison between pre-ICL with each other period; p3, Bonferroni adjusted P value for comparison between after 7 days with each other period; p4, Bonferroni adjusted P value for comparison between after I months with each other period; p5, Bonferroni adjusted P value for comparison between after 6 months with each other period; p6, Bonferroni adjusted P value for comparison between after 1 year and after 3 years.
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TABLE 2. Comparison Between Different Periods of UCVA for TICL Implantation After Corneal Crosslinking for Keratoconus UCVA Range Mean 6 SD Median F (p) Mean difference Mean difference Mean difference Mean difference Mean difference
CDVA Before ICL
After 7 Days
After 1 Month
After 6 Months
After 1 Year
After 3 Years
0.40–0.80 0.63 6 0.14 0.60
0.60–1.20 0.79 6 0.16 0.80
0.60–1.20 0.83 6 0.16 0.80 43.022* (,0.001) 0.206* (,0.001) 0.038 (0.135)
0.60–1.20 0.85 6 0.15 0.80
0.60–1.20 0.88 6 0.18 0.85
0.60–1.20 0.88 6 0.18 0.85
0.250* (,0.001) 0.081* (0.042) 0.044 (0.210)
0.250* (,0.001) 0.081* (0.042) 0.044 (0.210) 0.0 (2)
0.250* (,0.001) 0.081* (0.042) 0.044 (0.210) 0.0 (2) 0.0 (2)
(p1) (p2) (p3) (p4) (p5)
0.169* (0.002)
*Statistically significant at P # 0.05. p1, Bonferroni adjusted P value for comparison between pre-ICL with each other period; p2, Bonferroni adjusted P value for comparison between after 7 days with each other period; p3, Bonferroni adjusted P value for comparison between after 1 month with each other period; p4, Bonferroni adjusted P value for comparison between after 6 month with each other period; p5, Bonferroni adjusted P value for comparison between after 1 year and after 3 years; UCVA, uncorrected distant visual acuity.
Collagen crosslinking using riboflavin and UV light was recently introduced6,17; however, crosslinking alone stabilizes and stiffens the cornea by inducing more corneal collagen crosslinks of keratoconus, and the remaining refractive errors will still need to be corrected. After thoroughly searching the literature, we found only 2 published articles18,19 that were similar to our study. The first was published by Kymionis et al18 who described a case report of TICL implantation performed after corneal crosslinking. The second article was published by Fadlallah et al19 and included 16 eyes with previous corneal crosslinking for progressive keratoconus and then an implantation of TICL with an interval of 6 months and a follow-up period for only 6 months. Therefore, we believe that our study is the first reported work of its kind to include this number of studied eyes, and having a relatively long follow-up duration of 3 years. In this prospective nonrandomized clinical interventional study of 16 eyes, we aimed to determine whether the implantation of a TICL in corneas that had been crosslinked and showed refractive stability for at least 12 months is safe, predictable, and effective in correcting different ranges of myopia and astigmatism in eyes with early-stage keratoconus. We obtained very satisfactory refractive outcomes in predictability with all the eyes being within 0.5 D of the intended spherical equivalent; the mean spherical equivalent was ,0.25 D 3 years after the surgery. In addition, the astigmatism decreased significantly to nearly clinically insignificant values. Regarding visual outcomes, the efficacy was good with .81% of the eyes having a postoperative UDVA of $0.8 and all the operated eyes maintaining a CDVA or gaining multiple lines of CDVA. The results are similar to those obtained by Fadlallah et al,19 but our study had a longer follow-up duration (3 years). The efficacy and predictability of posterior chamber phakic toric IOLs in the treatment of myopia with low-to-high astigmatism in keratoconic eyes are supported by recent reports.11,20–22 There are 2 studies of TICL implantation in eyes with keratoconus that had not undergone crosslinking.23,24 The
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first study was performed by Kamiya et al23 on a very small sample (2 eyes of 2 patients with stable keratoconus). The other study was performed by Alfonso et al,24 who obtained very satisfactory refractive outcomes in predictability with all the eyes being within 1.00 D of the intended spherical equivalent; the mean spherical equivalent was ,0.25 D 12 months after surgery. In addition, astigmatism decreased significantly to nearly clinically insignificant values. Regarding visual outcomes, the efficacy was good with .60% of the eyes having a postoperative UDVA of $0.8 and 97% of the operated eyes maintaining a CDVA or gaining multiple lines of the CDVA. The results are consistent with our results, but it is difficult to directly compare with this study because of the difference in the number of cases and the crosslinking not being performed before the TICL implantation. The most commonly reported postoperative complications of the ICL implantation are anterior subcapsular cataract25–27 and increased IOP.28,29 Sanders30 reported that anterior subcapsular opacities and cataract occurred 5 years after surgery in the Food and Drug Administration trial. Although approximately 6% to 7% of eyes developed anterior subcapsular opacities $7 years after phakic IOL implantation, the opacity progressed to a clinically significant cataract in only 1% to 2% during the same period, with most cases being observed in older patients and in eyes with very high myopia. There were no cases of chronic increased postoperative IOP or anterior subcapsular cataract in our study. Another concern is the degree of vaulting of the implanted ICL and how it changes over time; a study performed by Kojima et al31 1 year after ICL implantation in 36 eyes showed that the mean vault was 0.53 6 0.25 mm. A result consistent with the results in our study, which showed a mean vault of 0.509 6 0.141 mm at 1 year postoperatively. We also demonstrated that a high vault gradually decreases over time. The reason for the decrease in the initial vaulting measures especially from the 1-week to 1-month period of the postoperative follow-up may be related to the residual viscoelastic material that was present between the ICL and the crystalline lens, although meticulous irrigation/ Ó 2014 Lippincott Williams & Wilkins
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aspiration was performed. A complete irrigation is often difficult because of the presence of a narrow space between the crystalline lens and the ICL. No complications occurred during the surgical procedures. No eye needed explantation or repositioning of the TICL. Decentration of the TICL optic was not observed, and no case of pupillary block was detected. It is preferable that TICL implantation not be performed until refraction and keratometry are stable after corneal collagen crosslinking. We suggest the following indications for TICL implantation in keratoconus: CDVA $20/50, clear central cornea, and stable refraction for at least 12 months after crosslinking. If these criteria are not met, a PKP would probably provide better visual outcomes. Thus, TICL implantation should not be considered a true alternative to PKP but rather an alternative treatment in cases of early stages of keratoconus with a relatively low irregular regular astigmatism. All intraocular procedures entail some degree of endothelial cell loss, and insertion of a phakic IOL induces between 2.1% and 7.6%.32 Postoperative endothelial loss is also an important issue. For the ICL, the 1-year endothelial cell loss rate was 5.17% in 1 study,33 and, in another, a cumulative decrease of 7.7% was seen in the endothelial cell density over 5 years.34 The reason for the discrepancy is possibly because of chronic low-grade inflammation.35 In conclusion, we found that correction of spherical and cylindrical refractive errors in keratoconic eyes by TICL implantation up to 3 years after crosslinking seems to have significantly better outcomes, particularly in the astigmatic component of refraction. The significant visual improvement after this procedure could be attributed to 2 factors; the effect of the crosslinking on flattening/ regularizing the cornea and the correcting effect of the TICL on a plane near the nodal point of the line of sight. We recommend meticulous repeated refraction of these eyes to obtain the subjective refraction and to calculate the ICL power using it to target postoperative emmetropia. Nevertheless, long-term randomized comparative prospective studies with large cohorts are needed to assess the stability and potential complications of the procedure and the possible combination with other treatments in cases of keratoconus progression and refraction change. REFERENCES 1. Wolf FR, Hoyer A, Spoerl E, et al. Collagen crosslinking with riboflavin and ultraviolet-A light in keratoconus: long-term results. J Cataract Refract Surg. 2008;34:796–801. 2. Kymes SM, Walline JJ, Zadnik K, et al. Quality of life in keratoconus. Am J Ophthalmol. 2004;138:527–535. 3. Maeno A, Naor J, Lee HM. Three decades of corneal transplantation: indications and patient characteristics. Cornea. 2000;19:7–11. 4. Caporossi A, Baiocchi S, Mazzotta C. Parasurgical therapy for keratoconus by riboflavin–ultraviolet type A rays induced cross-linking of corneal collagen: preliminary refractive results in an Italian study. J Cataract Refract Surg. 2006;32:837–845. 5. Meek KM, Tuft SJ, Huang Y. Changes in collagen orientation and distribution in keratoconus corneas. Invest Ophthalmol Vis Sci. 2005;46: 1948–1956.
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6. Wollensak G. Crosslinking treatment of progressive keratoconus: new hope. Curr Opin Ophthalmol. 2006;17:356–360. 7. Spoerl E, Wollensak G, Seiler T. Increased resistance of crosslinked cornea against enzymatic digestion. Curr Eye Res. 2004;29:35–40. 8. Spöerl E, Schreiber J, Hellmund K. Studies on the stabilization of the cornea in rabbits [in German]. Ophthalmologe. 2000;97: 203–206. 9. Kohlhaas M, Spoerl E, Schilde T. Biomechanical evidence of the distribution of cross-links in corneas treated with riboflavin and ultraviolet A light. J Cataract Refract Surg. 2006;32:279–283. 10. Coskunseven E, Onder M, Kymionis GD. Combined intacs and posterior chamber toric implantable collamer lens implantation for keratoconic patients with extreme myopia. Am J Ophthalmol. 2007;144: 387–389. 11. Sanders DR, Shneider D, Martin R, et al. Toric implantable collamer lens for moderate to high myopic astigmatism. Ophthalmology. 2007; 114:54–61. 12. Alfonso JF, Palacios A, Montés-Micó R. Myopic phakic STAAR collamer posterior chamber intraocular lenses for keratoconus. J Refract Surg. 2008;24:867–874. 13. Davis LJ, Schechtman KB, Wilson BS, et al. Longitudinal changes in visual acuity in keratoconus. Invest Ophthalmol Vis Sci. 2006;47: 489–500. 14. Zadnik K, Barr JT, Edrington TB, et al. Corneal scarring and vision in keratoconus: a baseline report from the collaborative longitudinal evaluation of keratoconus (CLEK) study; the CLEK study group. Cornea. 2000;19:804–812. 15. Mahadevan R, Arumugam AO, Arunachalam V, et al. Keratoconus— a review from a tertiary eye-care center. J Optom. 2009;2:166–172. 16. Gordon MO, Steger-May K, Szczotka-Flynn L, et al. Baseline factors predictive of incident penetrating keratoplasty in keratoconus. Am J Ophthalmol. 2006;142:923–930. 17. Wollensak G, Spoerl E, Seiler T. Riboflavin/ultraviolet-a-induced collagen crosslinking for the treatment of keratoconus. Am J Ophthalmol. 2003;135:620–627. 18. Kymionis GD, Grentzelos MA, Karavitaki AE, et al. Combined corneal collagen cross-linking and posterior chamber toric implantable collamer lens implantation for keratoconus. Ophthalmic Surg Lasers Imaging. 2011;42:e22–e25. 19. Fadlallah A, Dirani A, El Rami H, et al. Safety and visual outcome of Visian toric ICL implantation after corneal collagen cross-linking for keratoconus. J Refract Surg. 2013;29:84–89. 20. Kamiya K, Shimizu K, Igarashi A, et al. Comparison of collamertoric [corrected] contact lens implantation and wavefront-guided laser in situ keratomileusis for high myopic astigmatism. J Cataract Refract Surg. 2008;34:1687–1693; erratum, 2011. 21. Sanders DR, Sanders ML. Comparison of the toric implantable collamer lens and custom ablation LASIK for myopic astigmatism. J Refract Surg. 2008;24:773–778. 22. Alfonso JF, Fernández-Vega L, Fernandes P, et al. Collagen copolymer toric posterior chamber phakic intraocular lens for myopic astigmatism: one-year follow-up. J Cataract Refract Surg. 2010;36:568–576. 23. Kamiya K, Shimizu K, Ando W, et al. Phakictoric implantable collamer lens implantation for the correction of high myopic astigmatism in eyes with keratoconus. J Refract Surg. 2008;24:840–842. 24. Alfonso JF, Baamonde B, Madrid-Costa D, et al. Toric phakic intraocular collamer posterior chamber lenses to correct high degrees of myopic astigmatism. J Cataract Refract Surg. 2010;36:577–586. 25. Gonvers M, Bornet C, Othenin-Girard P. Implantable contact lens for moderate to high myopia; relationship of vaulting to cataract formation. J Cataract Refract Surg. 2003;29:918–924. 26. Sanders DR, Vukich JA. Incidence of lens opacities and clinically significant cataracts with the implantable contact lens: comparison of two lens designs; the ICL in treatment of myopia (ITM) study group. J Refract Surg. 2002;18:673–682. 27. Jiménez-Alfaro I, Benítez del Castillo JM, García-Feijoó J, et al. Safety of posterior chamber phakic intraocular lenses for the correction of high myopia; anterior segment changes after posterior chamber phakic intraocular lens implantation. Ophthalmology. 2001;108:90–99; discussion by SM MacRay, 99.
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28. Chung TY, Park SC, Lee MO, et al. Changes in iridocorneal angle structure and trabecular pigmentation with STAAR implantable collamer lens during 2 years. J Refract Surg. 2009;25:251–258. 29. Chun YS, Park IK, Lee HI, et al. Iris and trabecular meshwork pigment changes after posterior chamber phakic intraocular lens implantation. J Cataract Refract Surg. 2006;32:1452–1458. 30. Sanders DR. Anterior subcapsular opacities and cataracts 5 years after surgery in the visian implantable collamer lens FDA trial. J Refract Surg. 2008;24:566–570. 31. Kojima T, Maeda M, Yoshida Y, et al. Posterior chamber phakic implantable collamer lens: changes in vault during 1 year. J Refract Surg. 2010;26:327–332.
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Cornea Volume 33, Number 5, May 2014
32. Lovisolo CF, Reinstein DZ. Phakic intraocular lenses. Surv Ophthalmol. 2005;50:549–587. 33. Jiminez-Alfaro I, Benitez del Castillo JM, Garcia-Feijoo J, et al. Safety of posterior chamber phakic intraocular lenses for the correction of high myopia: anterior segment changes after posterior chamber phakic intraocular lens implantation. Ophthalmology. 2001;108: 90–99. 34. Alfonso JF, Baamonde B, Fernández-Vega L, et al. Posterior chamber collagen copolymer phakic intraocular lenses to correct myopia: five-year follow up. J Cataract Refract Surg. 2011;37:873–880. 35. Bozkurt E, Yazici AT, Yildirim Y, et al. Long-term follow-up of firstgeneration posterior chamber phakic intraocular lens. J Cataract Refract Surg. 2010;36:1602–1604.
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