Crosslinking treatment of progressive keratoconus: New hope

Department of Ophthalmology, Universitatsklinikum CGC, Dresden, Germany.
Current Opinion in Ophthalmology (Impact Factor: 2.5). 09/2006; 17(4):356-60. DOI: 10.1097/
Source: PubMed


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.
    Full-text · Article · Jul 2015 · Journal of Ophthalmology
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    • "The cornea transmits and reflects the light while protecting the inner contents of the eye. Corneal collagen cross-linking therapy has recently been introduced as a potential treatment option for halting the progression of keratoconus (Caporossi et al., 2010; Mazzotta et al., 2007; Wollensak, 2006). In this procedure, the strength and stiffness are increased by using the photosensitizer riboflavin solution and ultraviolet (UVA) to induce cross-links in the anterior portion of the corneal stroma (Søndergaard et al., 2013; Spoerl et al., 1998; Wollensak and Iomdina, 2009; Wollensak et al., 2003b). "
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    ABSTRACT: Cornea is a soft tissue with the principal function of transmitting and refracting light rays. The objective of the current study was to characterize possible effects of the riboflavin/UVA collagen cross-linking on corneal dynamic properties. The original corneal cross-linking protocol was used to induce cross-links in the anterior portion of the bovine cornea. A DMA machine was used to conduct mechanical tensile experiments at different levels of tensile strains. The samples were divided into a control group (n = 5) and a treated group (n = 5). All specimens were first stretched to a strain of 5% and allowed to relax for twenty minutes. After completion of the stress-relaxation experiment, a frequency sweep test with oscillations ranging from 0.01 to 10 Hz was performed. The same procedure was repeated to obtain the stress-relaxation and dynamic properties at 10% strain. It was observed that the collagen cross-linking therapy significantly increased the immediate and equilibrium tensile behavior of the bovine cornea (P < 0.05). Furthermore, for all samples in control and treated groups and throughout the whole range of frequencies, a significantly larger tensile storage modulus was measured at an axial strain of 10% compared to what was obtained at a tensile strain of 5%. Finally, it was noted that although this treatment procedure resulted in a significant increase in the storage and loss modulus at any axial strain and frequency (P < 0.05), it significantly reduced the ratio of the dissipated and stored energy during a single cycle of deformation. Therefore, it was concluded that while the riboflavin/UVA collagen cross-linking increased significantly corneal stiffness, it decreased significantly its damping capability and deformability. This reduced damping ability might adversely interfere with corneal mechanical performance. Copyright © 2015. Published by Elsevier Ltd.
    Full-text · Article · Apr 2015 · Experimental Eye Research
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    • "In this relatively new treatment option, the UVA irradiation with continuous application of riboflavin solution is used to introduce cross-links in the stromal layer and stiffen the cornea. Over the past few years, the effects of different parameters of this treatment option, e.g., UVA wavelength, UVA intensity, radiation time, and concentration of riboflavin solution, have been investigated (Coskunseven et al., 2009; Spoerl et al., 1998, 2007; Wollensak, 2006). In these studies, desirable changes in a specific parameter were considered as those which resulted in a higher enhancement of biomechanical properties. "
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    ABSTRACT: The collagen cross-linking is a relatively new treatment option for strengthening the cornea, delaying, and in some cases stopping the progression of keratoconus. The uniaxial tensile experiments are among the most commonly used techniques to assess the effectiveness of this therapeutic option in enhancing tensile properties. In the present study, we investigated the possible effects of hydration on stiffening effects of corneal collagen cross-linking procedure, as measured by the uniaxial tensile testing method. For this purpose, after cross-linking bovine corneas, we let the strips to dehydrate in air or swell in a solution until their thickness reached an average thickness of 0.5, 0.7, 0.9, 1.1, and 1.5mm. Using thickness as a representative of hydration, we divided corneal strips into five different groups and measured their stress-strain behavior by conducting uniaxial tensile experiments in mineral oil. It was observed that the collagen cross-linking treatment and hydration together affect the tensile behavior of the bovine cornea. While corneal collagen cross-linking resulted in a significant increase in the tensile stress-strain response of each thickness group (P<0.01), less hydrated collagen cross-linked samples showed a significantly stiffer response (P<0.01). A master curve was found for representing the tensile behavior of the collagen cross-linked bovine cornea at different levels of hydration. The results of the present research confirmed that the amount of mechanical stiffening of the corneal collagen cross-linking, as measured by uniaxial tensile testing, strongly depends on the hydration. Therefore, it is concluded that uniaxial tensile experiments could only be used to assess stiffening effects of the collagen cross-linking treatment if the hydration of specimens is fully controlled. Copyright © 2015 Elsevier Ltd. All rights reserved.
    Full-text · Article · Feb 2015 · Journal of Biomechanics
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