United States Multicenter Clinical Trial of Corneal Collagen Crosslinking for Keratoconus Treatment
TL;DR: Corneal collagen crosslinking was effective in improving the maximum keratometry value, CDVA, and UCVA in eyes with progressive keratoconus 1 year after treatment, with an excellent safety profile.
About: This article is published in Ophthalmology.The article was published on 2017-09-01. It has received 184 citations till now. The article focuses on the topics: Keratoconus & Corneal topography.
Citations
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TL;DR: The role of sex hormones as a control mechanism for KC onset and progression is discussed and evidence supporting the view that prolactin‐induced protein is an important hormonally regulated biomarker in KC is discussed.
88 citations
TL;DR: Corneal collagen crosslinking was effective in improving the maximum K value, CDVA, and UDVA in eyes with corneal ectasia 1 year after treatment, with an excellent safety profile.
83 citations
TL;DR: To compare results between standard and accelerated corneal collagen cross‐linking (CXL) for the treatment of progressive keratoconus, a comparison study is conducted with real-time data over a 12-month period.
Abstract: PURPOSE To compare results between standard and accelerated corneal collagen cross-linking (CXL) for the treatment of progressive keratoconus. METHODS We performed literature searches in PubMed, Cochrane Library, Web of Science, ISRCTN registry, ClinicalTrials.gov, and EMBASE for studies comparing conventional Dresden (C-CXL) and accelerated CXL (A-CXL). Outcomes were clinical results and changes in corneal properties. Weighted mean differences were used to evaluate the effects. RESULTS Here, 22 studies with 1158 eyes (C-CXL: 577 eyes; A-CXL: 581 eyes) were included. At the last follow-up, C-CXL was superior regarding minimum keratometry (p < 0.00001) and demarcation line depth (p < 0.00001), whereas A-CXL should be favoured when considering minimum corneal thickness (p = 0.0005). No differences in uncorrected and corrected distance visual acuity (p = 0.09 and 0.98), spherical equivalent (p = 0.11), spherical and cylindrical error (p = 0.29 and 0.32), maximal and average keratometry (p = 0.05 and 0.65), central corneal thickness (p = 0.15), corneal biomechanical properties (p ≥ 0.21 respectively), time of reepithelialization (p = 0.76), subbasal nerve density (p = 0.69), endothelial cell density (p = 0.30) and morphology (p ≥ 0.40 respectively) were found among both groups. CONCLUSION Consideration of less corneal thinning favours A-CXL, whereas the deeper demarcation line and greater changes in minimum keratometric values in C-CXL may indicate a higher treatment efficacy. Altogether, C-CXL, as well as A-CXL, provides successful results in the strengthening of corneal tissue.
72 citations
Cites background from "United States Multicenter Clinical ..."
...Hersh et al. (2017) reported 3 of 102 eyes having clinically significant corneal haze at 1 year after C-CXL....
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TL;DR: In this article, a review of crosslinking chemistries and polymers commonly used for preparing translatable hydrogels are outlined and their performance in biological systems is summarized, and examples of effective polymer/crosslinking chemistry combinations that have yielded clinically approved hydrogel products are specifically highlighted.
Abstract: Hydrogels are an important class of biomaterials with the unique property of high-water content in a crosslinked polymer network. In particular, chemically crosslinked hydrogels have made a great clinical impact in past years because of their desirable mechanical properties and tunability of structural and chemical properties. Various polymers and step-growth crosslinking chemistries are harnessed for fabricating such covalently crosslinked hydrogels for translational research. However, selecting appropriate crosslinking chemistries and polymers for the intended clinical application is time-consuming and challenging. It requires the integration of polymer chemistry knowledge with thoughtful crosslinking reaction design. This task becomes even more challenging when other factors such as the biological mechanisms of the pathology, practical administration routes, and regulatory requirements add additional constraints. In this review, key features of crosslinking chemistries and polymers commonly used for preparing translatable hydrogels are outlined and their performance in biological systems is summarized. The examples of effective polymer/crosslinking chemistry combinations that have yielded clinically approved hydrogel products are specifically highlighted. These hydrogel design parameters in the context of the regulatory process and clinical translation barriers, providing a guideline for the rational selection of polymer/crosslinking chemistry combinations to construct hydrogels with high translational potential are further considered.
65 citations
TL;DR: This review uniquely integrates the clinical and cellular aspects of both corneal trauma and disease and provides a comprehensive view of the most recent findings and potential therapeutics aimed at restoring cornea homeostasis.
52 citations
References
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TL;DR: Collagen crosslinking may be a new way for stopping the progression of keratectasia in patients with keratoconus and the need for penetrating keratoplasty might then be significantly reduced in keratconus.
2,576 citations
TL;DR: The past and present literature on corneal thinning disorders is reviewed, practical approaches to diagnosis and management are outlined and treatment ranges from simple spectacle correction to keratoplasty.
1,394 citations
TL;DR: Riboflavin−UVA‐induced collagen cross‐linking led to an increase in mechanical rigidity in porcine corneas and an even greater increase in human corneal rigidity, which can be explained by the relatively larger portion of the cornea being cross‐linked in the overall thinner human cornea.
Abstract: Results: There was a significant increase in corneal rigidity after cross-linking, indicated by a rise in stress in treated porcine corneas (by 71.9%) and human corneas (by 328.9%) and in Young’s modulus by the factor 1.8 in porcine corneas and 4.5 in human corneas. The mean central corneal thickness was 850 m 70 (SD) in porcine corneas and 550 40 m in human corneas. Conclusions: RiboflavinUVA-induced collagen cross-linking led to an increase in mechanical rigidity in porcine corneas and an even greater increase in human corneas. As collagen cross-linking is maximal in the anterior 300 m of the cornea, the greater stiffening effect in human corneas can be explained by the relatively larger portion of the cornea being cross-linked in the overall thinner human cornea. J Cataract Refract Surg 2003; 29:1780 –1785 © 2003 ASCRS and ESCRS
988 citations
"United States Multicenter Clinical ..." refers background in this paper
...Indeed, studies show that, immediately after CXL, stress measurement increases in human corneas by more than 300%.(18) By means of this corneal biomechanical strengthening, the essential clinical goal of CXL in keratoconus is to decrease disease progression over time....
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TL;DR: Results indicate long‐term stabilization and improvement after collagen crosslinking is an effective therapeutical option for progressive keratoconus, and thus, collagenCrosslinking was an effective therapeutic option forgressive keratconus.
Abstract: Purpose To prove the long-term dampening effect of riboflavin- and ultraviolet-A-induced collagen crosslinking on progressive keratoconus. Setting Department of Ophthalmology, C.G. Carus University Hospital, Dresden, Germany. Methods Four hundred eighty eyes of 272 patients with progressive keratoconus were included in this long-term retrospective study. The maximum follow-up was 6 years. At the first and all follow-up examinations, refraction, best corrected visual acuity (BCVA), corneal topography, corneal thickness, and intraocular pressure were recorded. Results The analysis included 241 eyes with a minimum follow-up of 6 months. The steepening decreased significantly by 2.68 diopters (D) in the first year, 2.21 D in the second year, and 4.84 D in the third year. The BCVA improved significantly (≥1 line) in 53% of 142 eyes in the first year, 57% of 66 eyes in the second year, and 58% of 33 eyes in the first year or remained stable (no lines lost) in 20%, 24%, and 29%, respectively. Two patients had continuous progression of keratoconus and had repeat crosslinking procedures. Conclusions Despite the low number of patients with a follow-up longer than 3 years, results indicate long-term stabilization and improvement after collagen crosslinking. Thus, collagen crosslinking is an effective therapeutical option for progressive keratoconus.
911 citations
TL;DR: Comparison of the currently used riboflavin/UVA approach with officially accepted guidelines regarding direct UV damage and the damage created by the induced free radicals shows that as long as the cornea treated has a minimum thickness of 400 μm, the corneal endothelium will not experience damage, nor will deeper structures such as lens and retina.
Abstract: Purpose To study potential damage to ocular tissue during corneal collagen cross-linking (X-linking) by means of the riboflavin/UVA (370 nm) approach. Methods Comparison of the currently used technique with officially accepted guidelines regarding direct UV damage and the damage created by the induced free radicals (photochemical damage). Results The currently used UVA radiant exposure of 5.4 mJ/cm and the corresponding irradiance of 3 mW/cm2 is below the known damage thresholds of UVA for the corneal endothelium, lens, and retina. Regarding the photochemical damage caused by the free radicals, the damage thresholds for keratocytes and endothelial cells are 0.45 and 0.35 mW/cm, respectively. In a 400-microm-thick cornea saturated with riboflavin, the irradiance at the endothelial level was 0.18 mW/cm, which is a factor of 2 smaller than the damage threshold. Conclusions After corneal X-linking, the stroma is depopulated of keratocytes approximately 300 microm deep. Repopulation of this area takes up to 6 months. As long as the cornea treated has a minimum thickness of 400 microm (as recommended), the corneal endothelium will not experience damage, nor will deeper structures such as lens and retina. The light source should provide a homogenous irradiance, avoiding hot spots.
764 citations
"United States Multicenter Clinical ..." refers background in this paper
...The original parameters for CXL suggested a minimum stromal thickness of 400 mm to attenuate the ultraviolet A power and thus prevent endothelial damage.(40,41) Indeed, in the study protocol, corneas needed to be swollen with a hypotonic riboflavin solution to the 400-mm threshold before proceeding with ultraviolet exposure....
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