Marcony R Santhiago, J Bradley Randleman
Over the past 20 years, corneal crosslinking (CXL) has been used by surgeons to halt progression in eyes with keratoconus. We reviewed the literature regarding the mechanism of action of CXL, the role of each of its components the strong biologic reaction, and their effects on cell interaction, proteins involved, wound healing, and cytotoxic reaction. CXL surgery involves a photochemical response in which ultraviolet light at a given wavelength and riboflavin participate. The combination of irradiation with UVA light and riboflavin leads to an intense process of apoptosis of keratocytes in the anterior stroma...
November 7, 2020: Experimental Eye Research
Sandra Hoyek, Nicolas Arej, Hala El Rami, Peggy Saba, Joelle Antoun
PURPOSE: To study the corneal flattening effect of cross-linking (CXL) overtime and to look for a potential association with preoperative topographic variables and the central depth of demarcation line (DDL). METHODS: 201 eyes of 146 patients (mean age of 31.2 ± 7.3 years) with progressive keratoconus who underwent CXL between June 2007 and December 2012 were enrolled in this retrospective study. Follow-up visits were performed at different time intervals for at least 5 years...
November 2, 2020: European Journal of Ophthalmology
Hamed Niyazmand, James McKelvie, Ye Li, Cameron McLintock
PURPOSE: To compare the visual and tomographic outcomes of epithelium-on and epithelium-off corneal collagen crosslinking (CXL) in an accelerated protocol in eyes with progressive keratoconus. METHODS: Sixty-one patients with progressive keratoconus (female patients, n = 30; male patients, n = 31) aged 17 and 48 years (mean age: 25.8 ± 6.2 yrs) were included in this study. Patients underwent either epithelium-off (n = 27) or epithelium-on (n = 34) CXL using an accelerated protocol...
October 19, 2020: Cornea
Gabriella Maria Fernandes-Cunha, Karen Mei Chen, Fang Chen, Peter Le, Ju Hee Han, Leela Ann Mahajan, Hyun Jong Lee, Kyung Sun Na, David Myung
Visually significant corneal injuries and subsequent scarring collectively represent a major global human health challenge, affecting millions of people worldwide. Unfortunately, less than 2% of patients who could benefit from a sight-restoring corneal transplant have access to cadaveric donor corneal tissue. Thus, there is a critical need for new ways to repair corneal defects that drive proper epithelialization and stromal remodeling of the wounded area without the need for cadeveric donor corneas. Emerging therapies to replace the need for donor corneas include pre-formed biosynthetic buttons and in situ-forming matrices that strive to achieve the transparency, biocompatibility, patient comfort, and biointegration that is possible with native tissue...
October 7, 2020: Scientific Reports
Hyeonjun Hong, Jeongho Kim, Hoseong Cho, Sang Min Park, Mansik Jeon, Hong Kyun Kim, Dong Sung Kim
Despite the potential of a collagen construct, consisting of a major extracellular matrix component of the native cornea, as a patch graft to treat the corneal perforation, there has still been difficulty in acquiring sufficient mechanical properties for clinical availability. This study developed a novel in situ photochemical crosslinking (IPC)-assisted collagen compression process, namely, the IPC-C2 process, to significantly enhance the mechanical properties of the collagen construct for the development of a collagenous patch graft...
October 1, 2020: Biofabrication
Angel A Zeitoune, Patrícia A Bersanetti, Paulo Schor, Luciana A Erbes, Carlos L Cesar, Javier Adur
Corneal cross-linking (CXL) is a common surgical procedure used to modify corneal biomechanics and stabilize keratoconus progression which is still under discussion. Its side effects, which are mostly related to anatomical unpredictability and stromal exposure, are the reason for the search for new CXL agents. In this work we have quantitatively evaluated the porcine corneal stroma architecture treated with collagen crosslinking agents such as riboflavin solutions and açai extract, using second harmonic generation microscopy...
September 25, 2020: International Journal of Biological Macromolecules
Hongxun Li, Taiwei Liu, Bokun Mu, Xinheng Zhao, Chao Xue, Min Shen, Vishal Jhanji, Yan Wang
In this study, we established an experimental human corneal stroma model of simulated cornea tissue composed of thin anterior cornea strips layers obtained from small incision lenticular extraction (SMILE) surgery. We investigated the biomechanical effect of ultraviolet-A- riboflavin cross-linking at different depths of corneal stroma model and correlated it with stromal microstructural changes examined by transmission electron microscopy (TEM). Corneal strips were harvested from fresh human corneal lenticules obtained after SMILE surgery...
June 18, 2020: Experimental Eye Research
Fang Chen, Peter Le, Gabriella M Fernandes-Cunha, Sarah C Heilshorn, David Myung
Biomaterials that mimic corneal stroma could decrease the need for donor corneal tissue and could decrease the prevalence of complications associated with corneal transplantation, including infection and rejection. We developed a bio-orthogonally crosslinked hyaluronate-collagen hydrogel which can fill corneal defects in situ without the need for any sutures, initiators, or catalysts. We studied the effects of biorthogonal crosslinking on the light transmittance of the hydrogel, which was greater than 97% water...
October 2020: Biomaterials
N S Anisimova, S I Anisimov, N F Shilova, A Yu Zemskaya, N A Gavrilova, S Y Anisimova
Corneal collagen cross-linking (CXL) is a procedure that aims to halt the progression of corneal ectasia in keratoconic eyes. It is achieved by inducing cross-links in the corneal stroma and extracellular matrix by exposing it to ultraviolet-A (370 nm) irradiation while it is filled with photosensitizer (riboflavin). According to the conventional protocol, the recommended de-epithelialized corneal thickness should be higher than 400 μm in order to avoid radiation damage to the corneal endothelium. However, in progressive keratoconus, corneal thickness is often close to or lower than this threshold of 400 μm, which limits the application of cross-linking for these patients...
2020: Vestnik Oftalmologii
M Ezzeldin, F Filev, J Steinberg, A Frings
PURPOSE: To review the clinical outcome of keratoconus patients after excimer laser treatment with combined riboflavin UV-A collagen crosslinking (CXL) treatment was reviewed in light of the UDVA, CDVA and HOA. METHODS: Following a PubMed-based literature review of studies on excimer laser treatment with combined riboflavin UV-A CXL published between 2009 and 2018, peer-reviewed English-written studies were evaluated using the GRADE approach (www.gradeworkinggroup...
May 2, 2020: International Ophthalmology
Xiaomin Sun, Xiangjing Yang, Wenjing Song, Li Ren
The emergence of innovative surgical procedures using partial thickness corneal transplant has created a need for the development of corneal grafts to replace pathologic corneal tissue. Corneal repair materials have been successfully prepared in the past 10 years, but they were difficult to be used in clinics because of the unbearable tension caused by interrupted suture during routine surgery. However, polycaprolactone (PCL), a medical polymer material, can solve this problem. Therefore, a hierarchical collagen (Col)-based corneal graft with curvature, consisting of a transparent core part composed of collagen in the center and a mechanically robust fixed part containing collagen and polycaprolactone in the edge, was used as a potential corneal graft for corneal repair and regeneration in this study...
January 14, 2020: ACS Omega
Samantha Bradford, Eric Mikula, Sun Woong Kim, Yilu Xie, Tibor Juhasz, Donald J Brown, James V Jester
Purpose: We have shown that nonlinear optical corneal crosslinking (NLO CXL) and stiffening can be achieved in ex vivo rabbit corneas using an 80-MHz, 760-nm femtosecond (FS) laser, however the required power was beyond the American National Standard Institute limit. The purpose of this study was to test the efficacy of amplified FS pulses to perform CXL to reduce power by increasing pulse energy. Methods: A variable numerical aperture laser scanning delivery system was coupled to a 1030-nm laser with a noncollinear optical parametric amplifier to generate 760 nm, 50 to 150 kHz amplified FS pulses with 79...
November 2019: Translational Vision Science & Technology
Yuan Wu, Wenjing Song, Yun Tang, Xiaoming Yan
PURPOSE: To evaluate the biomechanical efficacy after in vivo enzyme-induced corneal crosslinking in rabbit, using noninvasive imaging untreated Methods: The eyes of 10 white New Zealand rabbits were monolaterally treated with crosslinking (CXL) enzyme (transglutaminases [Tgases]). The contralateral eyes served as negative controls. In every rabbit, a 1 U/mL solution of Tgases was applied to the corneal surface. Corneal dynamic deformation by an air puff was measured using high-speed Scheimpflug imaging on day 14 after the procedure...
December 30, 2019: Ophthalmic Research
Rushita Shah, Pavel Stodulka, Katerina Skopalova, Petr Saha
The application of polymeric biomaterial scaffolds utilizing crosslinking strategy has become an effective approach in these days. In the present study, the development and characterization of collagen-chitosan hydrogel film has been reported on using dual crosslinking agent's, i.e., tannic acid and genipin simultaneously. Incorporation of genipin imparts a greenish-blue color to the polymeric film. The effect of dual crosslinking and their successful interaction within the matrix was evaluated by infrared analysis spectroscopy...
December 14, 2019: Polymers
E-M Konrad, D Röck, G Blumenstock, K U Bartz-Schmidt, T Röck
BACKGROUND AND PURPOSE: The corneal collagen crosslinking procedure has been clinically performed worldwide for approximately 20 years. The aim of the study was to analyze the long-term outcomes of corneal crosslinking at the University Eye Hospital in Tübingen. METHODS: In this retrospective study 136 consecutive eyes with progressive keratoconus from 107 patients were included. The observational period was from December 2008 to March 2018. The parameters analyzed were best corrected visual acuity (BCVA) and the keratometry values from elevation maps measured using a Scheimpflug camera...
November 13, 2019: Der Ophthalmologe: Zeitschrift der Deutschen Ophthalmologischen Gesellschaft
Yun Tang, Wenjing Song, Jing Qiao, Bei Rong, Yuan Wu, Xiaoming Yan
Purpose: Aim to assess the short-term effect of genipin collagen crosslinking (G-CXL) on corneal structure and biomechanical properties compared with ultraviolet A/riboflavin collagen crosslinking (UVA-CXL) in rabbit corneas. Methods: Right eyes of 40 healthy rabbits were divided into the 0.20% G-CXL group, 0.25% G-CXL group, UVA-CXL group, and control group. Anterior segment optical coherence tomography (ASOCT) and in vivo confocal microscopy (IVCM) were performed before, 7 days after, and 14 days after the CXL treatment...
2019: Molecular Vision
Tina B McKay, Shrestha Priyadarsini, Dimitrios Karamichos
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...
October 11, 2019: Cells
Laura Koivusalo, Maija Kauppila, Sumanta Samanta, Vijay Singh Parihar, Tanja Ilmarinen, Susanna Miettinen, Oommen P Oommen, Heli Skottman
Regeneration of a severely damaged cornea necessitates the delivery of both epithelium-renewing limbal epithelial stem cells (LESCs) and stroma-repairing cells, such as human adipose-derived stem cells (hASCs). Currently, limited strategies exist for the delivery of these therapeutic cells with tissue-like cellular organization. With the added risks related to suturing of corneal implants, there is a pressing need to develop new tissue adhesive biomaterials for corneal regeneration. To address these issues, we grafted dopamine moieties into hydrazone-crosslinked hyaluronic acid (HA-DOPA) hydrogels to impart tissue adhesive properties and facilitate covalent surface modification of the gels with basement membrane proteins or peptides...
December 2019: Biomaterials
Promita Bhattacharjee, Julia Fernández-Pérez, Mark Ahearne
Millions of people worldwide suffer from vision impairing conditions resulting from corneal injury or disease. Silk fibroin (SF) is an emerging biopolymer that has been used for several applications including the fabrication of bioengineered corneas and ocular prostheses. To improve the cell response to SF, riboflavin (RF) and all-trans retinoic acid (RA) were coupled onto SF matrices. RF is a photo-initiator that has previously been combined with ultraviolet light to crosslink corneal collagen while RA has been used to regulate the phenotype of corneal stromal cells and their extracellular matrix deposition...
December 2019: Materials Science & Engineering. C, Materials for Biological Applications
Philipp L Müller, Karin U Loeffler, Elisabeth Messmer, Frank G Holz, Georgios Perdikakis, Markus Kohlhaas, Martina C Herwig-Carl
PURPOSE: To investigate histopathologic, immunohistochemical, and electron microscopic findings in 8 keratoplasty specimens with a history of corneal collagen crosslinking (CXL) for keratoconus. Five new (hitherto unreported) and 3 previously published specimens were analyzed. METHODS: Corneal buttons of 8 keratoconus corneas (5-114 months after CXL) were compared with 5 keratoconus specimens without CXL and 5 normal corneas for morphological alterations. Corneal buttons were evaluated by light microscopy and immunohistochemistry using antibodies against CD34, PGP 9...
September 9, 2019: Cornea
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