Intraoperative and Postoperative Effects of Corneal Collagen Cross-linking on Progressive Keratoconus

Department of Ophthalmology, Istituto Clinico Humanitas, Via Manzoni 56, Rozzano 20089, Milan, Italy.
Archives of ophthalmology (Impact Factor: 4.4). 10/2009; 127(10):1258-65. DOI: 10.1001/archophthalmol.2009.205
Source: PubMed


To report intraoperative and 24-month refractive, topographic, tomographic, and aberrometric outcomes after corneal collagen cross-linking in progressive advanced keratoconus.
Prospective, nonrandomized single-center clinical study involving 28 eyes. Main outcome measures included uncorrected and best spectacle-corrected visual acuities, sphere and cylinder refraction, topography, tomography, aberrometry, and endothelial cell count evaluated at baseline and follow-up at 1, 3, 6, 12, and 24 months after treatment. Topography was also recorded intraoperatively.
Two years after treatment, mean baseline uncorrected and best spectacle-corrected visual acuities improved significantly (P = .048 and <.001, respectively) and mean spherical equivalent refraction decreased significantly (P = .03). Mean baseline flattest and steepest meridians on simulated keratometry, simulated keratometry average, mean average pupillary power, and apical keratometry all decreased significantly (P < .03). Deterioration of the Klyce indices was observed in the untreated contralateral eyes but not in treated eyes. Total corneal wavefront aberrations Z(0) (piston), Z(2) (defocus), and Z(7) (III coma) decreased significantly (P < or = .046). Mean 12-month baseline pupil center pachymetry and total corneal volume decreased significantly (P = .045). Endothelial cell counts did not change significantly (P = .13).
Two years postoperatively, corneal collagen cross-linking appears to be effective in improving uncorrected and best spectacle-corrected visual acuities in eyes with progressive keratoconus by significantly reducing corneal average pupillary power, apical keratometry, and total corneal wavefront aberrations.

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Available from: Elena Albé, Oct 03, 2015
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    • "It is important to mention here that the use of steroid eye drops and their duration after CXL highly depend on the ophthalmologists’ practice. In generally, steroids are administered 0-4 weeks after CXL treatment [5-8,11,22,27]. In contrast, we have used fluorometholone drops for minimum 3 months and found no increase in the mean intraocular pressure postoperatively (data not shown). Corneal thickness and posterior elevation at minimum pachymetry proved to be highly reliable diagnostic parameters of KC and to monitor the treatment efficacy after CXL [10]. "
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    ABSTRACT: Keratoconus (KC) is the most common primary corneal ectatic disease which has considerable importance in public health. Corneal collagen crosslinking (CXL) is a procedure to mitigate progression of KC and reduce demand for corneal transplantation. Although studies have proven the efficacy of CXL regarding corneal shape, none have investigated the effects of CXL on tear biomarkers which are useful tools to understand molecular mechanisms behind CXL. Our purpose was to determine the effect of CXL on tear mediators in patients with KC and analyze associations with corneal changes. Tear samples were collected pre-CXL from 26 eyes of 23 patients and during a 12-month follow-up. The mediators' concentration was measured by Cytometric Bead Array technology. Corneal topography parameters measured by Scheimpflug Camera included: Thinnest-corneal-thickness (ThCT), keratometry values (K1, K2), Radii-Minimum (Rmin), Keratoconus-Index (KI), Center-KI (CKI), Index-of-Height Asymmetry (IHA) and Index-of-Surface Variance (ISV). At baseline, KI was correlated negatively with chemokine (C-C motif) ligand 5 (CCL5) (p=0.015) and matrix metalloproteinase (MMP)-13 (p=0.007). At day 4, interleukin (IL)-6 and IL-8 increased, while IL-13, IL-17A, interferon (IFN)-γ, CCL5, MMP-13, epidermal growth factor (EGF), nerve growth factor (NGF) and plasminogen activator inhibitor (PAI-1) decreased significantly compared to pre-CXL concentrations (p≤0.02). At 6 months tissue plasminogen activator (t-PA) increased (p=0.02), while at 12 months Rmin increased (p≤0.004), and IL-6 and CXCL8 (p=0.005 and p=0.047) as well as K1, ISV and KI decreased. After 6 months CKI and ISV showed significant associations with IL-17A; CKI with IL-13 and ThCT with IL-13 (p≤0.02), while at 12 months there were reverse associations between ThCT and IL-6, IL-13, INFγ, CCL5 and PAI-1 (p≤0.02). Alterations of mediators in tear fluid after CXL associate with topographic changes highlight the fact that many mediators are involved in the complex mechanisms after CXL. Further studies on biomarkers to investigate the efficacy of CXL are needed.
    PLoS ONE 10/2013; 8(10):e76333. DOI:10.1371/journal.pone.0076333 · 3.23 Impact Factor
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    • "When the tenets of the Dresden protocol are not violated, the CXL procedure is believed to pose no threat to the corneal endothelium.[28] Studies have also confirmed that the corneal endothelium cell loss is not significant at 12 months after CXL.[8429] Such data is lacking with the combined T-CAT + CXL procedure. "
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    ABSTRACT: Purpose: To compare the outcome of Collagen cross-linking (CXL) with that following topography-guided customized ablation treatment (T-CAT) with simultaneous CXL in eyes with progressive keratoconus. Materials and Methods: This was a prospective, non-randomized single centre study of 66 eyes with progressive keratoconus. Of these, 40 eyes underwent CXL and 26 eyes underwent T-CAT + CXL. The refractive, topographic, tomographic and aberrometric changes measured at baseline, 1, 3 and 6 months post-operatively were compared between both groups. Results: After a mean follow-up of 7.7 ± 1.3 months, the mean retinoscopic cylinder decreased by 1.02 ± 3.16 D in the CXL group (P = 0.1) and 2.87 ± 3.22 D in the T-CAT + CXL group (P = 0.04). The Best corrected visual acuity increased by 2 lines or more in 10% of eyes in the CXL group and in 23.3% of eyes in the T-CAT + CXL group. The mean steepest-K reduced by 0.40 ± 3.71 D (P = 0.77) in the CXL group and by 2.91 ± 2.01D (P = 0.03) in the T-CAT + CXL group. The sag factor and surface asymmetry index showed no significant change in the CXL group but reduced by 3.59 ± 5.94 D (P = 0.01) and 0.72 ± 1.18 (P = 0.02) respectively in the T-CAT + CXL group. There was a significant increase in the highest posterior corneal elevation in both groups (9.57 ± 14.93 μ in the CXL group and 7.85 ± 9.25 μ in the T-CAT + CXL group, P ≤ 0.001 for both). There was significantly greater reduction of mean coma (P < 0.001) and mean higher-order aberrations (P = 0.01) following T-CAT + CXL compared to CXL. Conclusions: CAT + CXL is an effective approach to confer biomechanical stability and to improve the corneal contour in eyes with keratoconus and results in better refractive, topographic and aberrometric outcomes than CXL alone.
    Indian Journal of Ophthalmology 04/2013; 62(2). DOI:10.4103/0301-4738.111209 · 0.90 Impact Factor
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    • "Collagen cross-linking has gained increasing acceptance for strengthening corneal tissue during keratoconus and corneal ectasia (Wollensak et al., 2003a,b). The combined use of ultraviolet light (UVA) with riboflavin has been reported in the literature to achieve these results (Vinciguerra et al., 2009). "
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    ABSTRACT: To introduce femtosecond laser wound design combined with riboflavin/ultraviolet light-A (UVA) collagen cross-linking at the wound for penetrating (PKP) and anterior lamellar keratoplasty (ALK). Primary outcomes were intraocular pressure (IOP in mmHg) at burst point for the PKP group, and tensile strength (kPa) until dehiscence for the ALK group. Human corneoscleral rims (N = 20) were mounted on artificial anterior chambers. PKP specimens underwent FUR, femtosecond laser-cut without cross-linking, or conventional corneal transplantation. PKP maximum burst IOP with progressive suture removal was assessed by a digital manometer, in triplicate and by three observers. ALK involved whole human globes (N = 10) divided into three groups using a 200-micron, 8 mm diameter donor lenticule, with or without cross-linking. Cross-linked specimens were exposed to UVA light (3 mW/cm(2) irradiance, 3.4 J, 370 nm wavelength) for 30 min with 0.1% riboflavin (20% Dextran) applied every 2-min. ALK tensile strength was determined using a digital tensiometer. In PKP, burst IOP was 31.32 mmHg greater for corneas that underwent the UVA-riboflavin treatment than for those that did not (p < 0.05). There was no significant relationship (p = 0.719) established between cut design (femtosecond versus conventional). On multivariate analysis, there was a mean of 15.82 mmHg higher sustainable pressure for each stabilization suture present (p < 0.0001). In ALK, specimens comprised of human donor and human recipient tissue combined with UVA-riboflavin therapy experienced the greatest level of adhesion strength (954.7 ± 290.4 kPa) as shown by the force required to separate the tissues, and compared to non-cross-linked specimens. Electron microscopy of ALK specimens showed non-fused and fused longitudinal cross-linked collagen fibers as well as bridges, densities, attachment plaques and primitive plasmalemmal densities. Cross-linking effects of the FUR technique enable a stronger graft-recipient adhesion compared to conventional penetrating and anterior lamellar keratoplasty. Electron microscopy enabled visualization of cross-linked interface and potential bonding. The FUR approach may further lead to sutureless transplantation techniques in the future. ImagePlus Laser Eye Centre, Winnipeg, and University of Ottawa Eye Institute, Ottawa, Canada.
    Saudi Journal of Ophthalmology 07/2011; 25(3):261-7. DOI:10.1016/j.sjopt.2011.04.006
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