Collagen cross-linkage: A comprehensive review and directions for future research

Birmingham and Midland Eye Centre, Dudley Road, Birmingham B18 7QH, UK.
The British journal of ophthalmology (Impact Factor: 2.98). 09/2009; 94(8):965-70. DOI: 10.1136/bjo.2009.164228
Source: PubMed


Individuals with keratoconus form a significant proportion of patients for a practitioner specialising in corneal diseases. Yet it is a disease where the pathogenesis is poorly understood, and until recently, there has been no treatment apart from transplantation that could be offered that was curative or even capable of slowing the progression of the disease. Collagen cross-linking treatment using riboflavin and UV light has been developed to address this need, and the initial results are promising. The purpose of this review is to critically evaluate this treatment in light of the scientific basis for cross-linking, to highlight the strengths and limitations of the evidence in terms of efficacy and long-term safety, and finally to identify areas for future research in this area with a significant potential to change the way we treat our keratoconus patients. In addition, we hope that our unbiased review for the first time would bring together, in a concise fashion, scientific information for a practitioner contemplating on offering this treatment and to help inform their patients of its potential risks and benefits.

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    • "LOX is involved in corneal collagen and elastin cross-linking [105]. Artificial collagen fibre cross-linking following riboflavin and UV light exposure is a procedure currently being tested for the treatment of keratoconus and therefore this gene may have therapeutic implications [106]. Two SNPs (rs10519694 and rs2956540) in LOX showing nominal genome-wide significance were associated with keratoconus by family-based association testing that were also found to be significantly associated with keratoconus in case-control cohorts [107]. "
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    ABSTRACT: Keratoconus is a progressive thinning and anterior protrusion of the cornea that results in steepening and distortion of the cornea, altered refractive powers, and reduced vision. Keratoconus has a complex multifactorial etiology, with environmental, behavioral, and multiple genetic components contributing to the disease pathophysiology. Using genome-wide and candidate gene approaches several genomic loci and genes have been identified that highlight the complex molecular etiology of this disease. The review focuses on current knowledge of these genetic risk factors associated with keratoconus.
    Full-text · Article · Aug 2014 · Journal of Ophthalmology
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    • "The accurate measurement of central corneal thickness (CCT) is important in preparing for refractive surgery, monitoring corneal ectasia like keratoconus, complementing intraocular pressure (IOP), calculating the risk of progression from ocular hypertension to glaucoma, and studying corneal endothelial cell function after contact lens use.1-4 CCT is also a consideration when collagen cross-linking treatment is performed for progressive keratoconus.5 "
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    ABSTRACT: To evaluate reliability of Fourier-domain optical coherence tomography (OCT) (RTVue), time-domain OCT (Visante), and slit-lamp adapted ultrasonic pachymetry (SL-US) in the measurement of central corneal thickness (CCT). Thirty healthy volunteers visited our clinic 3 times and fifty eyes were measured by one physician. RTVue and Visante were randomly performed, and then SL-US, in which the ultrasound probe was inserted into the Goldmann tonometry mount, was done. During the second visit, each measurement was repeated 3 times. Measurements on the second visit were averaged, and agreement among the instruments was investigated with Bland-Altman plots. RTVue showed smaller repeatability coefficient than Visante and SL-US (4.7, 8.3, and 7.7 μm, respectively). Intersession reproducibility of RTVue and Visante was worse than their repeatability. CCT of RTVue was estimated to be maximally different by 11.8 μm from CCT of Visante and 8.8 μm from CCT of SL-US. The repeatability coefficient of SL-US was 7.7 μm and its reproducibility was similar to the repeatability. CCT measured by RTVue showed good reliability and generally agreed with Visante and SL-US. SL-US was as reliable as triple touching conventional US even with a single touch on the cornea.
    Full-text · Article · May 2012 · Yonsei medical journal
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    ABSTRACT: 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.
    Full-text · Article · Mar 2010 · Clinical and Experimental Ophthalmology
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