Collagen cross-linking: A new treatment paradigm in corneal disease-A review

Centre for Eye Research Australia, Department of Ophthalmology, University of Melbourne, Royal Victorian Eye & Ear Hospital, East Melbourne, Victoria, Australia.
Clinical and Experimental Ophthalmology (Impact Factor: 2.35). 03/2010; 38(2):141-53. DOI: 10.1111/j.1442-9071.2010.02228.x
Source: PubMed


The last 2 years has seen a marked increase in the prominence of corneal collagen cross-linking as a treatment strategy for progressive keratoconus. This interest has arisen from a body of laboratory evidence documenting the biomechanical and cellular changes induced by cross-linking. The findings of this research provide a plausible rationale for its use in keratoconus to retard the progression of this common disease. The rapidly growing number of clinical reports suggests, not only a consistent stabilizing effect of cross-linking, but that a variable improvement in corneal shape and visual function may also occur in some patients. However, the marked variation in the clinical course of keratoconus, together with the challenges of accurately evaluating refractive error, visual acuity and even corneal shape in this condition, demands further evidence from randomized controlled clinical trials. The aim of this review is to summarize the theoretical basis and risks of corneal collagen cross-linking, along with the available evidence for its use in keratoconus and other corneal disease states.

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Available from: Grant R Snibson
    • "At present, there are various contact and noncontact techniques available to measure CCT. Accuracy and repeatability of these techniques in measuring the CCT in keratoconus patients assume greater importance with the advent of newer prophylactic and therapeutic corneal intervention such as intrastromal corneal ring segment implantation,[4,5,6,7,8]collagen crosslinking,[9]and deep lamellar keratoplasty.[10]The CCT in keratoconus has previously been measured with anterior segment optical coherence tomography (AS-OCT), ultrasound pachymetry (USP), and Orbscan IIz (Bausch and Lomb Surgical Inc., San Dimas, CA, USA) and these studies have shown a high correlation between the techniques.[11]Though "
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    ABSTRACT: Purpose: To compare and determine the repeatability of central corneal thickness (CCT) measurements using four noncontact pachymetry instruments in eyes with keratoconus. Materials and Methods: The CCT of consecutive patients with keratoconus was measured during a single visit using the swept source optical coherence tomography (SS-OCT, Casia SS-1000°CT, Tomey, Nagoya, Japan), a rotating Scheimpflug camera system (Pentacam, Oculus Optikgerate GmbH, Wetzlar, Germany), scanning slit topographer (Orbscan IIz topography, Baush and Lomb Surgical Inc., San Dimas, CA, USA), and a hand-held spectral domain OCT (HHSD-OCT, Bioptigen Inc., Durham, North Carolina, USA). Test-retest variability, correlation between measurements and interdevice agreement were analyzed. Results: Fifty eyes of 25 participants were analyzed in this study. All measurement methods correlated well with each other (r > 0.9, P < 0.001). Mean ± standard deviation CCT measured by HHSD-OCT, Orbscan IIz, SS-OCT, and Pentacam was 462 ± 41 mm, 458 ± 41 mm, 454 ± 40 mm, and 447 ± 42 mm, respectively. While the HHSD-OCT over-estimated the CCT (P < 0.001), there was a good correlation between the measurements obtained from the other three devices. However, the numerical difference was high and this trend was seen in all the paired comparisons.Conclusions: Though the measurements by different devices correlated well, the numerical agreement may be inadequate for their interchangeable use in clinical practice. © 2015 Indian Journal of Ophthalmology | Published by Wolters Kluwer - Medknow.
    No preview · Article · Sep 2015 · Indian Journal of Ophthalmology
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    • "Previously, this photo-reductive cross-linking has been used in ophthalmology to treat keratoconus by using UVAirradiated riboflavin to enhance the stiffness of corneal collagen fibrils [23] [24] [25]. Although previous studies have indicated that the treatment of riboflavin by UVA improves the micromechanical properties of dentin and hybrid layers [18], there are few studies focusing specifically to the inhibition effect of crosslinking on dentin MMPs [17] [18], and no information is available of the effect on cathepsins. "
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    ABSTRACT: The aim of this study was to evaluate the effect of using UVA-induced crosslinking with or without riboflavin as photosensitizers on degradation of dentin matrix by dentin proteases. Demineralized dentin specimens (0.4×3×6mm(3), n=10/group) were subjected to: (RP1), 0.1% riboflavin-5 phosphate/UVA for 1min; (RP5), 0.1% riboflavin-5 phosphate/UVA for 5min; (R1), 0.1% riboflavin/UVA for 1min; (R5), 0.1% riboflavin-UVA for 5min; (UV1), UVA for 1min; (UV5), UVA for 5min. Specimens were incubated in 1mL zinc and calcium containing media for 1 day and 1 week. An untreated group served as control (CM). After incubation, the loss of dry mass of samples was measured and aliquots of media were analyzed for the release of C-terminal fragment telopeptide (ICTP vs. CTX) of collagen to evaluate for cathepsin K (CA-K) and total matrix metalloproteinase (MMP)-mediated degradation. Data were analyzed using repeated measures ANOVA at α=0.05. Although UVA radiation alone reduced dentin degradation, UVA-activated riboflavin or riboflavin-5 phosphate inhibited MMP and CA-K activities more than UVA alone. The effects of crosslinking were more pronounced in 7-day samples; only with CA-K were the effects of crosslinking with or without photosensitizer significantly different from controls in 1-day samples. The use of bioactive forms (RP) or longer treatment time did not result with better effect. The use of UVA crosslinking reduces dentin matrix degradation, especially with photosensitizers. Copyright © 2015 Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.
    Full-text · Article · Aug 2015 · Dental Materials
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    • "Martins et al. [5] demonstrated the antimicrobial properties of CxL against common pathogens. Moreover, it is already known that post-CxL corneas demonstrate increased tissue resistance to microbial enzymatic digestion [2]. "
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    ABSTRACT: Introduction Infectious keratitis following penetrating keratoplasty is a common postoperative complication. Intensive topical and systemic treatments do not always prevent the risk of graft failure. In this report we demonstrate the beneficial anti-microbial effect of corneal collagen cross-linking in a late-onset, sight-threatening, corneal graft ulcer. Case presentation A 57-year old Caucasian man underwent penetrating keratoplasty in his left eye, due to corneal bullosa after cataract extraction surgery. Twelve months after the penetrating keratoplasty, he visited our emergency service complaining of burning and foreign body sensation in his operated eye. Slit-lamp examination revealed a central, round-shaped ulcer of the graft. Due to poor response to the intensive topical antibiotic therapy, corneal collagen cross-linking was applied 3 days after admission, in an attempt to control the infection. Cultures indicated the predominance of methicillin-resistant Staphylococcus aureus infection. Five days after corneal collagen cross-linking treatment, the epithelium was completely re-epithelized, while the transparency of the transplanted cornea was gradually restored within the 12-month follow-up period. No relapses occurred. Conclusion Corneal collagen cross-linking seems to be a safe and effective therapeutic alternative in resistant cases of infectious keratitis following penetrating keratoplasty.
    Full-text · Article · Jun 2014 · Journal of Medical Case Reports
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