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      Efficacy and safety of transepithelial corneal collagen crosslinking surgery versus standard corneal collagen crosslinking surgery for keratoconus: a meta-analysis of randomized controlled trials

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          Abstract

          Background

          The aim of this study was to evaluate the efficacy and safety of transepithelial corneal collagen crosslinking (transepithelial CXL) versus standard corneal collagen crosslinking (epithelium-off CXL) on keratoconus.

          Methods

          Eligible studies were identified by systematically searching PubMed, the Cochrane Library and Embase. Topographic parameters, corrected distant visual acuity (CDVA), uncorrected distant visual acuity (UDVA), and corneal thickness (CT) were assessed by the pooled weighted mean differences (WMDs) of the change from baseline to the end of follow up. Quality was assessed according to Cochrane handbook. And we used Review Manager to analysis the included trials.

          Results

          Three trials involving 244 eyes were evaluated, with 111 eyes in the standard CXL group and 133 eyes in the transepithelial CXL group. The pooled results showed that there were significant differences between the two groups in maximum keratometry (mean difference = 1.05D, 95% CI 0.19 to 1.92, P = 0.02)),and the standard CXL is more effective in decreasing the maximum keratometry at least 12 months after operation; the transepithelial CXL group gained more improvement in CDVA (mean difference = −0.07, 95% CI -0.12 to −0.02, P = 0.007);there were no significant differences in uncorrected distant visual acuity (UDVA) between the two groups (mean difference = −0.03, 95% CI -0.20 to 0.15, P = 0.75). A similar change was found in corneal thickness (mean difference = 4.35, 95% CI -0.43 to 9.13, P = 0.07)).

          Conclusions

          The standard CXL is more effective in decreasing the maximum keratometry than the transepithelial CXL; the transepithelial CXL provided favorable visual outcomes; they both exhibit similar safety.

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          Most cited references25

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          Riboflavin/ultraviolet-a–induced collagen crosslinking for the treatment of keratoconus

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            Keratoconus: an inflammatory disorder?

            Keratoconus has been classically defined as a progressive, non-inflammatory condition, which produces a thinning and steepening of the cornea. Its pathophysiological mechanisms have been investigated for a long time. Both genetic and environmental factors have been associated with the disease. Recent studies have shown a significant role of proteolytic enzymes, cytokines, and free radicals; therefore, although keratoconus does not meet all the classic criteria for an inflammatory disease, the lack of inflammation has been questioned. The majority of studies in the tears of patients with keratoconus have found increased levels of interleukin-6 (IL-6), tumor necrosis factor-α(TNF-α), and matrix metalloproteinase (MMP)-9. Eye rubbing, a proven risk factor for keratoconus, has been also shown recently to increase the tear levels of MMP-13, IL-6, and TNF-α. In the tear fluid of patients with ocular rosacea, IL-1α and MMP-9 have been reported to be significantly elevated, and cases of inferior corneal thinning, resembling keratoconus, have been reported. We performed a literature review of published biochemical changes in keratoconus that would support that this could be, at least in part, an inflammatory condition.
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              Photochemical kinetics of corneal cross-linking with riboflavin.

              To model the photochemical kinetics of corneal cross-linking with riboflavin (Rf) and confirm the model through measured oxygen concentration experiments under varying energy input conditions by UV-A irradiance and temperature modulation in ex vivo porcine cornea. A theoretical model was developed to describe the corneal cross-linking photochemical kinetics of Rf. After instillation with drops of Rf solution in distilled water, de-epithelialized porcine corneas were exposed to 365-nm ultraviolet light (UV-A) under varying irradiance and temperature. Oxygen concentration in the cornea at a known depth was monitored during UV-A illumination with a dissolved oxygen fiberoptic microsensor. Data from the oxygen experiments were used to confirm the model. On the basis of the known chemical reactions and diffusion rates of Rf and oxygen into the cornea, the authors developed a theoretical model consistent with corneal oxygen consumption experimental results during UV-A irradiation under different conditions. Oxygen concentration in the cornea is modulated by UV-A irradiance and temperature and quickly decreased at the beginning of UV-A exposure. The time-dependence of both Type-I and Type-II photochemical mechanisms in corneal cross-linking with Rf are discussed. Using a chemical kinetics modeling approach, the authors developed a simple model that is in agreement with their experimental results on oxygen consumption in the cornea during corneal cross-linking with Rf. It is suggested that the main photochemical kinetics mechanism is the direct interaction between Rf triplets and reactive groups of corneal proteins, which leads to the cross-linking of the proteins mainly through radical reactions.
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                Author and article information

                Contributors
                wenwei60306@163.com
                hospitalref@163.com
                Journal
                BMC Ophthalmol
                BMC Ophthalmol
                BMC Ophthalmology
                BioMed Central (London )
                1471-2415
                28 December 2017
                28 December 2017
                2017
                : 17
                : 262
                Affiliations
                ISNI 0000 0004 4666 9789, GRID grid.417168.d, Department of Ophthalmology, , Tongde Hospital of Zhejiang Province, ; 234 Gucui Road, Hangzhou, 310012 China
                Article
                657
                10.1186/s12886-017-0657-2
                5745766
                29282020
                97c6c6fa-1ba2-4350-b6a0-e1b172e9efbd
                © The Author(s). 2017

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 30 July 2017
                : 11 December 2017
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2017

                Ophthalmology & Optometry
                keratoconus,transepithelial corneal collagen crosslinking,standard corneal collagen crosslinking,maximum keratometry,visual acuity,corneal thickness,meta analysis

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