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Cornea collagen crosslinking

Laura Koivusalo, Jennika Karvinen, Eetu Sorsa, Ilari Jönkkäri, Jari Väliaho, Pasi Kallio, Tanja Ilmarinen, Susanna Miettinen, Heli Skottman, Minna Kellomäki
Corneal blindness is a worldwide problem, plagued by insufficient amount of high-quality donor tissue. Cell therapy using human adipose stem cells (hASCs) has risen as an alternative to regenerate damaged corneal stromal tissue, the main structural and refractive layer of the cornea. Herein we propose a method to deliver hASCs into corneal defects in hyaluronan (HA)-based hydrogels, which form rapidly in situ by hydrazone crosslinking. We fabricated two different HA-based hydrazone-crosslinked hydrogels (HALD1-HACDH and HALD2-HAADH), and characterized their swelling, degradation, mechanical, rheological and optical properties and their ability to support hASC survival...
April 1, 2018: Materials Science & Engineering. C, Materials for Biological Applications
Hamed Hatami-Marbini, Sandeep M Jayaram
Purpose: The purpose of this study was to characterize the relation between corneal hydration and stiffening effects of the UVA/riboflavin collagen crosslinking treatment and to investigate how artificially swelling the cornea prior to this treatment procedure affects tensile property improvement. Methods: Porcine corneas were collagen crosslinked in vitro at different hydration levels using a number of hypoosmolar and isoosmolar riboflavin solutions. Thickness of the specimens prior to crosslinking was taken as a proxy for their hydration and was used to divide them into different thickness groups...
February 1, 2018: Investigative Ophthalmology & Visual Science
Alina Cantemir, Anisia-Iuliana Alexa, Bogdan Gabriel Galan, Nicoleta Anton, Roxana Elena Ciuntu, Ciprian Danielescu, Dorin Chiselita, Danut Costin
The purpose of this retrospective study was to report the results of iontophoretic corneal collagen crosslinking (I-CXL) with riboflavin and ultraviolet A irradiation in patients affected by keratoconus, each with thinnest pachymetry values of <400 μ (with epithelium) and not treatable using standard epithelium-off technique.Fifteen eyes of 15 patients affected by progressive keratoconus and with thinnest pachymetry values <400 μ underwent I-CXL. The uncorrected (UDVA) and corrected (CDVA) distance visual acuity, maximum and minimum keratometry (K max and K min) readings, corneal thickness at the thinnest point (CTTP), endothelial cell density (ECD), and intraocular pressure (IOP) were assessed before I-CXL, at 1, 3, 6, and 12 months postoperatively...
November 2017: Medicine (Baltimore)
Jaganmohan R Jangamreddy, Michel K C Haagdorens, M Mirazul Islam, Philip Lewis, Ayan Samanta, Per Fagerholm, Aneta Liszka, Monika K Ljunggren, Oleksiy Buznyk, Emilio I Alarcon, Nadia Zakaria, Keith M Meek, May Griffith
Short collagen-like peptides (CLPs) are being proposed as alternatives to full-length collagen for use in tissue engineering, on their own as soft hydrogels, or conjugated to synthetic polymer for mechanical strength. However, despite intended clinical use, little is known about their safety and efficacy, mechanism of action or degree of similarity to the full-length counterparts they mimic. Here, we show the functional equivalence of a CLP conjugated to polyethylene glycol (CLP-PEG) to full-length recombinant human collagen in vitro and in promoting stable regeneration of corneal tissue and nerves in a pre-clinical mini-pig model...
January 17, 2018: Acta Biomaterialia
Jiri Nohava, Michael Swain, Stefan J Lang, Philip Maier, Sonja Heinzelmann, Thomas Reinhard, Philipp Eberwein
UVA-crosslinking is used for treatment of corneal diseases such as keratoconus in order to stabilize the corneal tissue by crosslinking of the collagen fibers. It has been shown that the crosslinking treatment leads to a stiffening of the central corneal tissue. However, knowledge of lateral extent of the corneal stiffening as well as a systematic study of the mechanical response of human cornea is still missing. In our study we measured the stiffness (elastic modulus) of the anterior surface of healthy and crosslinked human corneas by instrumented indentation using a spherical indenter...
January 10, 2018: Journal of Biomedical Materials Research. Part A
Sabine Kling, Arthur Hammer, Emilio A Torres Netto, Farhad Hafezi
Purpose: We studied changes in gene transcription after corneal crosslinking (CXL) in the rabbit cornea in vivo and identified potential molecular signaling pathways. Methods: A total of 15 corneas of eight male New-Zealand-White rabbits were de-epithelialized and equally divided into five groups. Group 1 served as an untreated control. Groups 2 to 5 were soaked with 0.1% riboflavin for 20 minutes, which in Groups 3 to 5 was followed by UV-A irradiation at a fluence of 5...
December 2017: Translational Vision Science & Technology
Chameen Samarawickrama, Ayan Samanta, Aneta Liszka, Per Fagerholm, Oleksiy Buznyk, May Griffith, Bruce Allan
PURPOSE: To describe the use of collagen-based alternatives to cyanoacrylate glue for the sealing of acute corneal perforations. METHODS: A collagen analog comprising a collagen-like peptide conjugated to polyethylene glycol (CLP-PEG) and its chemical crosslinker were tested for biocompatibility. These CLP-PEG hydrogels, which are designed to act as a framework for corneal tissue regeneration, were then tested as potential fillers in ex vivo human corneas with surgically created full-thickness perforations...
November 22, 2017: Cornea
Samantha M Bradford, Eric R Mikula, Dongyul Chai, Donald J Brown, Tibor Juhasz, James V Jester
The purpose of this study was to develop and test a nonlinear optical device to photoactivate riboflavin to produce spatially controlled collagen crosslinking and mechanical stiffening within the cornea. A nonlinear optical device using a variable numerical aperture objective was built and coupled to a Chameleon femtosecond laser. Ex vivo rabbit eyes were then saturated with riboflavin and scanned with various scanning parameters over a 4 mm area in the central cornea. Effectiveness of NLO CXL was assessed by evaluating corneal collagen auto fluorescence (CAF)...
October 1, 2017: Biomedical Optics Express
Bahar Aslan, Selcan Guler, Atakan Tevlek, Halil Murat Aydin
Corneal tissue engineering efforts to obtain corneal tissue matrices through various types of materials for the replacement of damaged tissues. In this study, three different corneal constructs were prepared and evaluated in terms of morphological, optical, and biological characteristics. Type-I collagen was used to obtain collagen foam scaffolds through dehydrothermal crosslinking, while poly(l-lactic acid) (PLLA) was used to produce both random and aligned oriented electrospun corneal constructs. Bovine corneas were decellularized as third matrix...
October 12, 2017: Journal of Biomedical Materials Research. Part B, Applied Biomaterials
Zackery Oakey, Kevin Thai, Sumit Garg
Introduction: The cornea may become infected and perforated after epithelium-on collagen crosslinking. Case presentation: A healthy 33-year-old male who underwent corneal collagen crosslinking in both eyes developed a purulent keratitis and bilateral corneal perforations, requiring bilateral penetrating keratoplasties. He was exposed to methicillin resistant staphylococcus aureus (MRSA) by a family member with a tracheostomy and was treated with MRSA-directed antibiotics. After prolonged recovery and treatment of his infection, he had acceptable but limited uncorrected visual acuity, with excellent corrected visual acuity...
2017: GMS Ophthalmology Cases
Bushra Akbar, Rana Intisar-Ul-Haq, Mazhar Ishaq, Sabahat Arzoo, Kashif Siddique
OBJECTIVE: The purpose of this study was to evaluate the safety and efficacy of transepithelial corneal collagen cross linking (TE-CXL) with modified riboflavin and accelerated UVA irradiance in thin corneas with pachymetry less than 400 microns at thinnest point, untreatable by epithelium off corneal collagen cross linking (CXL) in adult Pakistani population with progressive keratoconus. METHODS: This quasi experimental study included twenty six eyes of 26 patients with progressive keratoconus who underwent accelerated transepithelial CXL in Armed forced institute of ophthalmology with 12 months follow up...
May 2017: Pakistan Journal of Medical Sciences Quarterly
Xiaokun Wang, Shoumyo Majumdar, Garret Ma, Jeeyeon Sohn, Samuel C Yiu, Walter Stark, Awad Al-Qarni, Deepak P Edward, Jennifer H Elisseeff
Purpose: To evaluate the crosslinking effect of functionalized chondroitin sulfate (CS) in an ex vivo rabbit cornea model. Methods: Chondroitin sulfate molecules were chemically modified with the N-hydroxysuccinimide (NHS) group. Enucleated rabbit eyes were crosslinked with 2, 5, or 10 mg/mL CS-NHS solution for 30 or 60 minutes. The CS-NHS penetration, corneal swelling ratio, Young's modulus, and ultrastructure of the crosslinked corneas were characterized. In addition, rabbit corneas were further treated with a collagenase-chondroitinase solution to create an ex vivo keratoconus (KC)-like model...
August 1, 2017: Investigative Ophthalmology & Visual Science
Weiwei Xu, Ye Tao, Liqiang Wang, Yifei Huang
BACKGROUND Some myopia patients with unsatisfactory corneas consider corneal refractive surgery for different reasons. Accelerated corneal collagen crosslinking (ACXL) is an effective method to enhance the resistance of the cornea. The present investigation was designed to evaluate the changes of biomechanical properties in patients with myopia and thin corneas after femtosecond-laser in situ keratomileusis (FS-LASIK) concurrent with ACXL. MATERIAL AND METHODS A prospective study was designed. A total of 22 eyes of 11 myopia astigmatism patients with unsatisfactory corneas were enrolled...
July 27, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
Patricia Gallego-Muñoz, Lucía Ibares-Frías, Elvira Lorenzo, Susana Marcos, Pablo Peréz-Merino, Nandor Bekesi, Irene E Kochevar, M Carmen Martínez-García
Purpose: To evaluate corneal wound healing after treatment with a new collagen crosslinking protocol using rose bengal dye and green light (RGX). Methods: One cornea of 20 New Zealand rabbits was de-epithelialized (DE) in an 8-mm diameter circle and, in another group (n = 25), the DE corneas were then stained with 0.1% rose bengal for 2 minutes and exposed to green light (532 nm) for 7 minutes (RGX). The contralateral eyes without treatment acted as controls. The animals were clinically followed including fluorescein staining and pachymetry...
July 1, 2017: Investigative Ophthalmology & Visual Science
Yirui Zhu, Peter S Reinach, Hanlei Zhu, Qiufan Tan, Qinxiang Zheng, Jia Qu, Wei Chen
Corneal collagen cross-linking (CXL) halts human corneal ectasias progression by increasing stromal mechanical stiffness. Although some reports describe that this procedure is effective in dealing with some infectious and immunologic corneal thinning diseases, there is a need for more animal models whose corneal thickness more closely resemble those occurring in these patients. To meet this need, we describe here high-intensity protocols that are safe and effective for obtaining CXL in rat corneas. Initially, a range of potentially effective UVA doses were evaluated based on their effectiveness in increasing tissue enzymatic resistance to dissolution...
2017: PloS One
P Maier, T Reinhard
In patients with keratoconus, a progressive, ectatic disease of the cornea, the shape of the cornea is continuously changing leading to a reduction in visual acuity by progressive myopia and more and more (irregular) astigmatism. The symptomatic treatment consists of the prescription of glasses or special gas-permeable rigid contact lenses. Corneal tomography is generally used for diagnosis. After initial diagnosis of keratoconus, regular tomographic follow-ups should be performed. If clinically significant progression is found and confirmed by repeated measurements, riboflavin UVA collagen crosslinking should be offered to the patients...
June 2017: Der Ophthalmologe: Zeitschrift der Deutschen Ophthalmologischen Gesellschaft
P L Müller, K U Löffler, M Kohlhaas, F G Holz, M C Herwig-Carl
Keratoconus is a relatively common (1 : 2000) bilateral disease leading to a change in biochemical and biomechanical corneal structure as well as thinning and ectasia. For more than 10 years, crosslinking has been a therapeutic option in cases of progression. Using riboflavin and UVA-radiation, the anterior corneal stroma (300 µm) gets stiffened by crosslinking of collagen fibers. When protocols and limitations are adhered, the procedure is described to be effective and of low-risk. This review gives an overview about physiologic and pathologic changes in keratoconic corneas before and after crosslinking...
May 3, 2017: Klinische Monatsblätter Für Augenheilkunde
Tai-Xiang Liu, Zheng Wang
AIM: To strengthen the biomechanics of collagen by crosslinking rabbit scleral collagen with genipin to develop a new therapy for preventing myopic progression. METHODS: Ten New Zealand rabbits were treated with 0.5 mmol/L genipin injected into the sub-Tenon's capsule in the right eyes. Untreated contralateral eyes served as the control. The treated area was cut into scleral strips measuring 4.0 mm×10.0 mm for stress-strain measurements (n=5). The remaining five treated eyes were prepared for histological examination...
2017: International Journal of Ophthalmology
Yunfei Han, Yanyun Xu, Wei Zhu, Yuling Liu, Zhen Liu, Xiaoxiao Dou, Guoying Mu
Purpose. To analyze the outcomes and difference after UVA/riboflavin corneal collagen crosslinking (CXL) in four different corneal thickness groups of patients with progressive keratoconus. Methods. Retrospective study. Eyes with progressive keratoconus after CXL were divided into 4 subgroups as follows: group 1, thinnest corneal thickness (TCT) ≤ 400 µm; group 2, 400 µm < TCT ≤ 450 µm; group 3, 450 µm < TCT ≤ 500 µm; group 4, TCT ≥ 500 µm. Baseline, 6-month, and 12-month visual acuity, corneal topography, TCT, and endothelial cell density were evaluated...
2017: Journal of Ophthalmology
Jui-Teng Lin, Da-Chuan Cheng
OBJECTIVE: Analysis of the crosslink time, depth and efficacy profiles of UV-light-activated corneal collagen crosslinking (CXL). METHODS: A modeling system described by a coupled dynamic equations are numerically solved and analytic formulas are derived for the crosslinking time (T*) and crosslinking depth (z*). The z-dependence of the CXL efficacy is numerically produced to show the factors characterizing the profiles. RESULTS: Optimal crosslink depth (z*) and maximal CXL efficacy (Ceff) have opposite trend with respective to the UV light intensity and RF concentration, where z* is a decreasing function of the riboflavin concentration (C0)...
2017: PloS One
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