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
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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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    • "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.
    Dental Materials 08/2015; 31(10). DOI:10.1016/ · 3.77 Impact Factor
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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.
    Journal of Medical Case Reports 06/2014; 8(1):180. DOI:10.1186/1752-1947-8-180
    • "Young keratoconus patients are likely to need one or more repeated grafts during their lifetime. Cross-linking avoids the removal of any corneal structural tissue (only the surface epithelial cells are removed and these grow back mostly within two days).[21] "
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    ABSTRACT: Corneal collagen cross-linking with riboflavin, also known as collagen cross-linking (CXL), involves the application of riboflavin solution to the eye that is activated by illumination with ultraviolet A (UVA) light. We survey here the topographic corneal changes one year after CXL in patients with corneal keratoconus. This prospective randomized clinical trial study comprised 66 patients with progression of keratoconus during one year who were enrolled at Feiz University Referral Eye Center in Isfahan. Before and after the operation, patients were examined with slit lamp and funduscopic examinations and measurement of uncorrected visual acuity (UCVA), and best spectacle-corrected visual acuity (BSCVA) was done with a logarithm of minimal angle of resolution (logMAR) scale. Corneal topographic and pachymetry values were derived from Orbscan II. The paired t-test test was used for statistical analyses with SPSS software version 20 (SPSS Inc., Chicago, IL, USA). All 66 patients completed postoperative follow-up at 12 months. The mean age of the patients was 22.4 ± 5.4 years (range: 18-29 years). Thirty-six (54.55%) subjects were men and 30 (45.45%) were women. The mean preoperative sphere was -2.66 ± 2.14 diopter (D), the mean cylinder was -3.97 ± 2.29, and the mean spherical equivalent (SE) was -4.64 ± 2.56. Postoperatively, the mean sphere was -2.22 ± 2.57 D, the mean cylinder was -3.60 ± 2.40 D, and SE was -4.02 ± 2.93 D (P = 0.037). SE also demonstrated a mean difference of 0.62 ± 0.37 D significantly (P = 0.006). The mean diameter of preoperative posterior best-fit sphere (BFS) was 6.33 ± 0.35mm (range: 5.51-7.73 mm) before operation, and it improved to 6.28 ± 0.34mm (range: 4.36-6.13 mm) after operation; the difference was significant (P = 0.039). Our study showed a significant improvement in topographic corneal changes and refractive results in patients with corneal ectasia after CXL.
    Journal of research in medical sciences 10/2013; 18(10):882-6. · 0.65 Impact Factor
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