Crosslinking treatment of progressive keratoconus: New hope

Department of Ophthalmology, Universitatsklinikum CGC, Dresden, Germany.
Current Opinion in Ophthalmology (Impact Factor: 2.64). 09/2006; 17(4):356-60. DOI: 10.1097/
Source: PubMed

ABSTRACT A new method has been introduced for the treatment of progressive keratoconus using collagen crosslinking by the photosensitzer riboflavin and ultraviolet A-light. Biomechanical measurements have shown an impressive increase in corneal rigidity of 328.9% in human corneas after crosslinking.
The 3 and 5-year results of the Dresden clinical study have shown that in all treated 60 eyes the progression of keratoconus was at least stopped ('freezing'). In 31 eyes there also was a slight reversal and flattening of the keratoconus by up to 2.87 diopters. Best corrected visual acuity improved slightly by 1.4 lines. So far, over 150 keratoconus patients have received crosslinking treatment in Dresden. Laboratory studies have revealed that the maximum effect of the treatment is in the anterior 300 mum of the cornea. As for the corneal endothelium, a cytotoxic level for endothelium was found to be 0.36 mW/cm which would be reached in human corneas with a stromal thickness of less than 400 mum.
Collagen crosslinking by the photosensitzer riboflavin and ultraviolet A-light is an effective means for stabilizing the cornea in keratoconus. Collagen crosslinking might become the standard therapy for progressive keratoconus in the future diminishing significantly the need for corneal transplantation. Preoperative pachymetry and individual control of the ultraviolet A-irradiance before each treatment are mandatory. The treatment parameters must not be varied.

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    • "Refractive surgery in high myopia with thinner corneas and borderline topography is a challenging decision, with the most feared complication being regression and postoperative ectasia [1] [2] [3] [4]. Collagen cross-linking (CXL) has been proven to be an effective modality to strengthen and stabilize the cornea in keratoconus and ectasia after corneal refractive surgery [5] [6] [7] [8] [9] [10] [11]. "
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    ABSTRACT: Purpose. To study the safety and clinical outcomes of ReLEx SMILE with accelerated cross-linking in individuals with thinner corneas, borderline topography, and higher refractive errors. Methods. Eligible patients first underwent SMILE procedure for correction of myopic refractive error. Following the removal of lenticule, 0.25% riboflavin in saline was injected into the interface and allowed to diffuse for 60 seconds. Finally, eye was exposed to UV-A radiation of 45 mW/cm(2) for 75 seconds through the cap. Total energy delivered was 3.4 J/cm(2). Results. 40 eyes of 20 patients with mean age of 26.75 ± 5.99 years were treated. Mean follow-up was 12 months ± 28.12 days. Mean spherical equivalent (SE) was -5.02 ± 2.06 D preoperatively and -0.24 ± 0.18 D postoperatively. The mean central corneal thickness (CCT) and keratometry changed from 501 ± 25.90 µm to 415 ± 42.26 µm and 45.40 ± 1.40 D to 41.2 ± 2.75 D, respectively. Mean uncorrected visual acuity (UCVA) was 20/25 or better in all eyes. No eyes lost lines of corrected distant visual acuity (CDVA). There were no complications like haze, keratitis, ectasia, or regression. Conclusion. Based on the initial clinical outcome it appears that SMILE Xtra may be a safe and feasible modality to prevent corneal ectasia in susceptible individuals.
    Journal of Ophthalmology 01/2015; 2015(6):263412. DOI:10.1155/2015/263412 · 1.94 Impact Factor
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    • "The concept of using collagen cross-linking photochemically induced, for increasing corneal stiffness, as a conservative method to stabilize ectasia progression was first conceived in Germany in the 1990s by Theo Seiler and collaborators [1] [2] [3] [4]. Collagen cross-linking (CXL) opened a new horizon for conscious biomechanical manipulation of the cornea [5], which uses the concept of biomechanical customization of therapeutic and refractive corneal surgery [6]. "
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    ABSTRACT: Corneal cross-linking (CXL) is increasingly performed in ophthalmology with high success rates for progressive keratoconus and other types of ectasia. Despite being an established procedure, some molecular and clinical aspects still require additional studies. This review presents a critical analysis of some established topics and others that are still controversial. In addition, this review examines new technologies and techniques (transepithelial and ultrafast CXL), uses of corneal CXL including natural products and biomolecules as CXL promoters, and evidence for in vitro and in vivo indirect effectiveness.
    Journal of Ophthalmology 08/2014; 2014(890823):9 pages. DOI:10.1155/2014/890823 · 1.94 Impact Factor
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    • "Riboflavin, also known as vitamin B 2 (belonging to the flavin group), is a photo-sensitizer that is excited into its triplet state when irradiated, generating reactive oxygen species (ROS) (Wollensak, 2006). The ROS can react further with various molecules inducing chemical covalent bonds bridging amino groups of collagen fibrils (type II photochemical reaction), inducing cross links which increase corneal stiffness (Wollensak, 2006). The precise molecular interactions of such ROS within the corneal stroma is not yet fully understood, although some progress has been made to improve insight into the effect of CXL on the cornea at the molecular level (Hayes et al., 2013; Meek and Hayes, 2013; McCall et al., 2010; Brummer et al., 2011). "
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    ABSTRACT: The purpose of this project was to assess anterior and posterior corneal stromal elasticity after corneal collagen cross linking (CXL) treatment in human cadaver eyes using Atomic Force Microscopy (AFM) through indentation. Twenty four human cadaver eyes (12 pairs) were included in this study and divided into 2 groups (6 pairs per group). In both groups, the left eye (OS) served as a control (no riboflavin or CXL treatment was performed) and the right eye (OD) underwent CXL treatment (30 minutes of riboflavin pretreatment followed by 30 minutes of exposure to 3mW/cm(2) of ultraviolet light). In group 1, the anterior stroma was exposed by manual delamination of approximately 50μm of the corneal stroma including Bowman's membrane. In group 2, the posterior stroma was exposed by delamination of the anterior 50% of the corneal stroma including Bowman's membrane. Delamination was performed after crosslinking treatment in the case of the treated eyes. In all eyes, the stromal elasticity was quantified using AFM through indentation. Young's modulus of elasticity for the anterior cornea (group 1) was 245.9±209.1kPa (range: 82.3 - 530.8 kPa) for the untreated control eyes, and 467.8±373.2kPa (range: 157.4 - 1126 kPa) for the CXL treated eyes. Young's modulus for the posterior cornea (group 2) was 100.2±61.9kPa (range: 28.1 - 162.6 kPa) for the untreated control eyes and 66.0±31.8kPa (range: 31.3 - 101.7 kPa) for the CXL treated eyes. Young's modulus of the anterior stroma significantly increased after CXL treatment (p=0.024), whereas the posterior stroma did not demonstrate a significant difference in Young's modulus after CXL treatment (p=0.170). The anterior stroma was stiffer than the posterior stroma for both the control and CXL treatment groups (p=0.077 and p=0.023, respectively). Our findings demonstrate that stiffness of the anterior corneal stroma after CXL treatment seems to increase significantly, while the posterior stroma does not seem to be affected by CXL.
    Experimental Eye Research 08/2013; 116. DOI:10.1016/j.exer.2013.07.028 · 3.02 Impact Factor
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