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Effect of collagen supplementation on osteoarthritis symptoms: a meta-analysis of randomized placebo-controlled trials.
García-Coronado, JM, Martínez-Olvera, L, Elizondo-Omaña, RE, Acosta-Olivo, CA, Vilchez-Cavazos, F, Simental-Mendía, LE, Simental-Mendía, M
International orthopaedics. 2019;(3):531-538
Abstract
PURPOSE Osteoarthritis (OA) is one of the most common causes of disability and a prevalent chronic disease. The use of collagen is growing due to the satisfactory results in the treatment of OA. However, the possible beneficial effects of collagen for the treatment of OA are currently controversial. The aim of the present meta-analysis was to evaluate the effect of collagen-based supplements on OA symptoms. METHODS PubMed-Medline, Scopus, and Google Scholar databases were searched for randomized placebo-controlled trials evaluating the effect of orally administered collagen on OA symptoms using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scale and/or the Visual Analog Scale (VAS). Meta-analysis was conducted using a random-effects model and a generic inverse variance method. Heterogeneity was tested using the I2 statistic index. RESULTS Collagen treatment showed a significant reduction in the score of total WOMAC index (WMD - 8.00; 95% CI - 13.04, - 2.95; p = 0.002). After subgroup analysis of the WOMAC subscores, the collagen supplementation revealed a significant decrease in the stiffness subscore (WMD - 0.41; 95% CI - 0.74, - 0.08; p = 0.01), whereas the pain (WMD - 0.22; 95% CI - 1.58, 1.13; p = 0.75) and functional limitation (WMD - 0.62; 95% CI - 5.77, 4.52; p = 0.81) subscores did not have significant differences. Finally, a significant reduction was found in the VAS score after collagen administration (WMD - 16.57; 95% CI - 26.24, - 6.89; p < 0.001). CONCLUSION The results of this meta-analysis showed that collagen is effective in improving OA symptoms by the decrease of both total WOMAC index and VAS score.
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Mechanisms of Collagen Crosslinking in Diabetes and Keratoconus.
McKay, TB, Priyadarsini, S, Karamichos, D
Cells. 2019;(10)
Abstract
Collagen crosslinking provides the mechanical strength required for physiological maintenance of the extracellular matrix in most tissues in the human body, including the cornea. Aging and diabetes mellitus (DM) are processes that are both associated with increased collagen crosslinking that leads to increased corneal rigidity. By contrast, keratoconus (KC) is a corneal thinning disease associated with decreased mechanical stiffness leading to ectasia of the central cornea. Studies have suggested that crosslinking mediated by reactive advanced glycation end products during DM may protect the cornea from KC development. Parallel to this hypothesis, riboflavin-mediated photoreactive corneal crosslinking has been proposed as a therapeutic option to halt the progression of corneal thinning by inducing intra- and intermolecular crosslink formation within the collagen fibrils of the stroma, leading to stabilization of the disease. Here, we review the pathobiology of DM and KC in the context of corneal structure, the epidemiology behind the inverse correlation of DM and KC development, and the chemical mechanisms of lysyl oxidase-mediated crosslinking, advanced glycation end product-mediated crosslinking, and photoreactive riboflavin-mediated corneal crosslinking. The goal of this review is to define the biological and chemical pathways important in physiological and pathological processes related to collagen crosslinking in DM and KC.
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Collagen Cross-Linking in the Management of Microbial Keratitis.
Bonzano, C, Di Zazzo, A, Barabino, S, Coco, G, Traverso, CE
Ocular immunology and inflammation. 2019;(3):507-512
Abstract
Increasing resistance to antimicrobial agents has contributed to an elevated risk of complications of infectious keratitis. Corneal collagen cross-linking (CXL) has been widely adopted for the management of keratoconus and post-refractive surgery corneal ectasia. It has recently been introduced as an option for treating keratitis due to multidrug resistant organisms. The purpose of this review is to discuss the rationale, safety, and evidence for CXL in infectious keratitis and its possible effect on ocular surface inflammation. Published data show that CXL is effective and safe as an adjunct to antibiotic treatment in selected cases of bacterial keratitis. The benefit of CXL probably varies according to the etiology of the infection.
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Collagen-binding proteins: insights from the Collagen Toolkits.
Farndale, RW
Essays in biochemistry. 2019;(3):337-348
Abstract
The Collagen Toolkits are libraries of 56 and 57 triple-helical synthetic peptides spanning the length of the collagen II and collagen III helices. These have been used in solid-phase binding assays to locate sites where collagen receptors and extracellular matrix components bind to collagens. Truncation and substitution allowed exact binding sites to be identified, and corresponding minimal peptides to be synthesised for use in structural and functional studies. 170 sites where over 30 proteins bind to collagen II have been mapped, providing firm conclusions about the amino acid distribution within such binding sites. Protein binding to collagen II is not random, but displays a periodicity of approximately 28 nm, with several prominent nodes where multiple proteins bind. Notably, the vicinity of the collagenase-cleavage site in Toolkit peptide II-44 is highly promiscuous, binding over 20 different proteins. This may reflect either the diverse chemistry of that locus or its diverse function, together with the interplay between regulatory binding partners. Peptides derived from Toolkit studies have been used to determine atomic level resolution of interactions between collagen and several of its binding partners and are finding practical application in tissue engineering.
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Corneal Cross-Linking: The Science Beyond the Myths and Misconceptions.
Rubinfeld, RS, Caruso, C, Ostacolo, C
Cornea. 2019;(6):780-790
Abstract
PURPOSE There has been a recent explosion in the variety of techniques used to accomplish corneal cross-linking (CXL) for the treatment of ectatic corneal diseases. To understand the success or failure of various techniques, we review the physicochemical basis of corneal CXL and re-evaluate the current principles and long-standing conventional wisdom in the light of recent, compelling, and sometimes contradictory research. METHODS Two clinicians and a medicinal chemist developed a list of current key topics, controversies, and questions in the field of corneal CXL based on information from current literature, medical conferences, and discussions with international practitioners of CXL. RESULTS Standard corneal CXL with removal of the corneal epithelium is a safe and efficacious procedure for the treatment of corneal ectasias. However, the necessity of epithelium removal is painful for patients, involves risk and requires significant recovery time. Attempts to move to transepithelial corneal CXL have been hindered by the lack of a coherent understanding of the physicochemistry of corneal CXL. Misconceptions about the applicability of the Bunsen-Roscoe law of reciprocity and the Lambert-Beer law in CXL hamper the ability to predict the effect of ultraviolet A energy during CXL. Improved understanding of CXL may also expand the treatment group for corneal ectasia to those with thinner corneas. Finally, it is essential to understand the role of oxygen in successful CXL. CONCLUSIONS Improved understanding of the complex interactions of riboflavin, ultraviolet A energy and oxygen in corneal CXL may provide a successful route to transepithelial corneal CXL.
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Combined application of prophylactic corneal cross-linking and laser in-situ keratomileusis - a review of literature.
Chan, TCY, Ng, ALK, Chan, KKW, Cheng, GPM, Wong, IYH, Jhanji, V
Acta ophthalmologica. 2017;(7):660-664
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Abstract
Laser in-situ keratomileusis (LASIK) is safe and effective laser refractive procedures in treating refractive errors. However, regression of treatment and iatrogenic keratectasia remain to be a major concern, especially in treating thin cornea with high ametropia. Collagen cross-linking (CXL) is an effective method in stopping keratoconus progression through increasing the biomechanical strength of the cornea. Adjuvant cross-linking to refractive procedures can theoretically help prevent regression and reduce the risk of keratectasia development by increasing the mechanical stability of cornea. During the procedure, riboflavin is directly applied to the corneal stroma, thereby reducing the need of de-epithelialization as in the conventional protocol for keratoconus. Currently, there is still no consensus regarding the indication of CXL during refractive procedure, nor any standardized treatment protocol. This article aims to summarize the current evidence regarding the use of adjuvant CXL in LASIK.
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Efficacy of Corneal Collagen Cross-Linking for the Treatment of Keratoconus: A Systematic Review and Meta-Analysis.
Meiri, Z, Keren, S, Rosenblatt, A, Sarig, T, Shenhav, L, Varssano, D
Cornea. 2016;(3):417-28
Abstract
PURPOSE To examine the efficacy of corneal collagen cross-linking (CXL) for the treatment of keratoconus (KCN). METHODS A systemic literature review and meta-analysis of ocular functional and structural parameters of patients with KCN undergoing cross-linking procedures were performed using PubMed and the web of science. A literature search was performed for relevant peer-reviewed publications on population-based studies. Data were analyzed with R software (Meta library), and heterogeneity was assessed with the Cochran Q and I. A random-effects model was used for high heterogeneity; otherwise a fixed model was used. Sensitivity analysis of particular tested groups was used to explain high heterogeneity. The main outcome measures extracted from the articles were corrected distance visual acuity, uncorrected distance visual acuity, and maximum K. RESULTS An improvement in visual acuity of 1 to 2 Snellen lines was found 3 months or more after undergoing CXL. Changes were more pronounced in uncorrected visual acuity. Some topography parameters were found to be improved (0.6-1 diopters) 12 to 24 months after CXL. The refractive cylinder improved by 0.4 to 0.7 diopters. Endothelial cell density decreased by 225 cells per square millimeter in the first 3 months and thereafter returned to normal. Corneal thickness was reduced by 10 to 20 μm in the year following CXL but not after 24 months. No changes in intraocular pressure were noted. CONCLUSIONS CXL is a safe and effective method for halting the deterioration of KCN, while slightly improving visual function.
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Riboflavin for corneal cross-linking.
O'Brart, DP
Drugs of today (Barcelona, Spain : 1998). 2016;(6):331-46
Abstract
Corneal collagen cross-linking (CXL) with riboflavin and ultraviolet A (UVA) radiation is the first therapeutic modality that appears to arrest the progression of keratoconus and other corneal ectasias. Riboflavin is central to the process, acting as a photosensitizer for the production of oxygen singlets and riboflavin triplets. These free radicals drive the CXL process within the proteins of the corneal stroma, altering its biomechanical properties. Riboflavin also absorbs the majority of the UVA radiation, which is potentially cytotoxic and mutagenic, within the anterior stroma, preventing damage to internal ocular structures, such as the corneal endothelium, lens and retina. Clinical studies report cessation of ectatic progression in over 90% of cases and the majority document significant improvements in visual, keratometric and topographic parameters. Clinical follow-up is limited to 5-10 years, but suggests sustained stability and enhancement in corneal shape. Sight-threatening complications are rare. The optimal stromal riboflavin dosage for CXL is as yet undetermined.
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Corneal Collagen Cross-Linking for Infectious Keratitis: A Systematic Review and Meta-Analysis.
Papaioannou, L, Miligkos, M, Papathanassiou, M
Cornea. 2016;(1):62-71
Abstract
PURPOSE To assess the efficacy of corneal collagen cross-linking (CXL) in the management of infectious keratitis. METHODS Comprehensive literature search was performed in MEDLINE/PubMed and Cochrane Central Register of Controlled Trials using combinations of the following search terms: "corneal collagen cross linking" or "photoactivated riboflavin" or "UVA light and riboflavin" and "infectious keratitis" or "corneal ulcer." Last search was on March 19, 2015. Extracted data from individual studies were summarized and summary proportions of eyes healed and complications for different subgroups were estimated. RESULTS Twenty-five studies were included (2 randomized controlled trials, 13 case series, and 10 case reports) with a total of 210 eyes of 209 patients, of which 175 eyes underwent CXL. Causative microorganisms were bacteria, fungi, acanthamoeba, and Herpes simplex virus in 96, 32, 11, and 2 cases, respectively. Coinfections were present in 13 and cause was inconclusive in 21 cases. Sixteen of 175 eyes received no additional antibiotics, whereas 159 underwent CXL as an adjunct to antimicrobial treatment. Proportion of eyes healed with CXL was 87.2% (95% confidence interval (CI), 81.9%, 91.8%). For bacterial keratitis, the proportion of eyes healed was 85.7% (95% CI, 78.5%, 91.7%), whereas 10/11 and 25/32 eyes with acanthamoeba and fungal keratitis, respectively, were healed (available data not sufficient to provide a valid proportion analysis). Treatment resulted in corneal melting and tectonic keratoplasty in both Herpes simplex virus cases. CONCLUSIONS CXL seems promising in the management of infectious keratitis, excluding viral infections. However, more randomized controlled trials are required to assess its efficacy.
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[Biochemical markers of bone metabolism and their importance].
Obermayer-Pietsch, B, Schwetz, V
Zeitschrift fur Rheumatologie. 2016;(5):451-8
Abstract
Laboratory analyses of biochemical markers for bone and mineral metabolism can play a key role in the assessment of patients with osteoporosis. They may help to assess bone turnover in the diagnostic work-up and aid decision-making as well as selection of pharmaceutical therapy options. Recent publications on therapy response have shown that biochemical markers of bone turnover are valuable tools for the evaluation of therapy success in individual osteoporosis patients and the assessment of bone mineral density gain during therapy.