Determining the efficacy of corneal crosslinking in progressive keratoconus

Malik, Sidra; Humayun, Sadia; Nayyar, Shahzad; Ishaq, Mazhar

doi:10.12669/pjms.332.11690

Cited by 10 publications

(8 citation statements)

References 17 publications

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“…This technique, developed by Spoerl and Wollensak (Raiskup and Spoerl, 2013; Spoerl et al, 1998; Wollensak et al, 2003a), works when activation of riboflavin within the corneal stroma induces the production of oxygen free radicals which in turn induce covalent crosslinking of collagen fibrils (Kamaev et al, 2012; Raiskup and Spoerl, 2013). Induced crosslinking enhances blue collagen autofluorescence (CAF) and has been shown to produce a 2–3 fold increase in corneal elastic modulus, lasting increased stiffness in human corneas up to 300% (Bradford et al, 2016, 2017; Wollensak and Iomdina, 2009; Wollensak et al, 2003a), and at least one diopter of corneal flattening lasting a year or longer (De Bernardo et al, 2015; Elling et al, 2017; Hersh et al, 2017; Kanellopoulos and Asimellis, 2015; Malik et al, 2017; Raiskup-Wolf et al, 2008; Shalchi et al, 2015; Vinciguerra et al, 2009; Wollensak et al, 2003a).…”

Section: Introductionmentioning

confidence: 99%

“…This treatment has many known effects on corneal tissue, including a dose dependent cellular toxicity, corneal haze, collagen fiber thickening up to 12% within the crosslinked region, and possibly straightening of the collagen fibers (De Bernardo et al, 2015; Kanellopoulos and Asimellis, 2015; Malik et al, 2017; Shalchi et al, 2015; Wollensak et al, 2003a, 2004b). In particular, keratocytes and endothelial cells are both at risk of damage, and cell death occurs within the crosslinked volume (Kozobolis et al, 2016; Kruger et al, 2011; Wollensak et al, 2003b, 2007, 2004a).…”

Section: Introductionmentioning

confidence: 99%

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Collagen fiber crimping following in vivo UVA-induced corneal crosslinking

Bradford

Mikula

Juhász

et al. 2018

Experimental Eye Research

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The purpose of this study was to measure collagen fiber crimping (CFC) using nonlinear optical imaging of second harmonic generated (SHG) signals to determine the effects of UVA-riboflavin induced corneal collagen crosslinking (UVA CXL) on collagen structure. Two groups, four rabbits each, were treated in the right eye with standard UVA CXL. In vivo confocal microscopy was performed at 1, 2, and 4 weeks after treatment for the first group and up to three months for the second group to measure epithelial/stromal thickness and corneal haze during recovery. Rabbits were sacrificed at one and three months, respectively, and their corneas fixed under pressure. Regions of crosslinking were identified by the presence of collagen autofluorescence (CAF) and then collagen structure was imaged using SHG microscopy. The degree of CFC was determined by measuring the percentage difference between the length of the collagen fiber and the linear distance traveled. CFC was measured in the central anterior and posterior CXL region, the peripheral non-crosslinked region in the same cornea, and the central cornea of the non-crosslinked contralateral eye. No change in corneal thickness was detected after one month, however the stromal thickness surpassed its original baseline thickness at three months by 25.9 μm. Corneal haze peaked at one month and then began to clear. Increased CAF was detected in all CXL corneas, localized to the anterior stroma and extending to 42.4 ± 3.4% and 47.7 ± 7.6% of the corneal thickness at one and three months. There was a significant (P < 0.05) reduction in CFC in the CAF region in all eyes averaging 1.007 ± 0.006 and 1.009 ± 0.005 in one and three month samples compared to 1.017 ± 0.04 and 1.016 ± 0.06 for controls. These results indicate that there is a significant reduction in collagen crimping following UVA CXL of approximately 1%. One possible explanation for this loss of crimping could be shortening of the collagen fibers over the CXL region.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Collagen fiber crimping following in vivo UVA-induced corneal crosslinking

Bradford

Mikula

Juhász

et al. 2018

Experimental Eye Research

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“…[28] C. opaca is distributed in northern hilly areas of Pakistan, such as Abbottabad, Murree, Margalla Hills and Kashmir. [29] The plant is also found in India, Burma and Sri Lanka. [30] It thrives best on sandy or rocky soils and also grows in shady moist places, forest edges and agricultural fields.…”

Section: Habit and Habitatmentioning

confidence: 99%

Carissa opaca: A plant with great potential for future drugs for degenerative and infectious diseases

Izhar

Ahmed

2016

ChemistrySelect

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Emergence of new diseases and development of complications in the old ones, coupled with safety, efficacy and affordability factors associated with existing medicines, have necessitated continuous quest for new remedies. Plants being a virtually unending reservoir of potential bioactive natural products hold great hope for more effective, safer and affordable therapeutic agents. In order to facilitate these studies, it is therefore desirable to publish reviews on medicinal plants. The present review is an effort to cover ethnomedicinal properties and research work done on medicinal plant, Carissa opaca (Apocynaceae), which is traditionally used for a number of purposes, including jaundice, hepatitis, rheumatism and asthma. Pharmacologically, different parts of plant have been studied for various bioactivities, such as, antioxidant, antimicrobial, anti‐cancer, anti‐diabetic, antipyretic, anti‐inflammatory, hepatoprotective and cytotoxic. Phytochemical investigations have resulted in the isolation of many natural products including terpenoids and flavonoids. As the extensive literature review suggests, C. opaca holds great promise for novel therapeutic remedies for various degenerative and pathological ailments. More rigorous, in vitro and in vivo, analyses and clinical studies are, therefore, recommended.

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“…1,2 The standard, US Food and Drug Administration-approved version of this technique uses ultraviolet-A (UVA) irradiation to excite the photosensitizer, riboflavin (Rf), imbibed into the patient's corneal stroma, causing the production of oxygen free radicals that in turn induce collagen crosslinking (CXL) within the corneal stroma. 3,4 While this technique is clinically successful in causing corneal stiffening and flattening, 1,[5][6][7][8][9][10][11][12][13][14][15] it is still far from ideal for many reasons. Chief among these reasons are the low precision of the technique and the method of Rf application.…”

Section: Introductionmentioning

confidence: 99%

Enhanced Transepithelial Riboflavin Delivery Using Femtosecond Laser-Machined Epithelial Microchannels

Bradford

Mikula

Xie

et al. 2020

Trans. Vis. Sci. Tech.

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This study describes a femtosecond laser (FS) approach to machine corneal epithelial microchannels for enhancing riboflavin (Rf) penetration into the cornea prior to corneal crosslinking (CXL). Methods: Using a 1030-nm FS laser with 5-to 10-μJ pulse energy, the corneal epithelium of slaughterhouse rabbit eyes was machined to create 2-μm-diameter by 25-μmlong microchannels at a density of 100 or 400 channels/mm 2. Rf penetration through the microchannels was then determined by applying 1% Rf in phosphate-buffered saline for 30 minutes followed by removal of the cornea and extraction from the central stromal button. Stromal Rf concentrations were then compared to those obtained using standard epithelial debridement or 0.01% benzalkonium chloride (BAK) to disrupt the epithelial barrier. Results: Microchannels formed using a 5-μJ/pulse at a density of 400 channels/mm 2 achieved a stromal Rf concentration that was 50% of that achieved by removal of the corneal epithelium and imbibing with 1% Rf. Stromal Rf levels were also equal to that of debrided corneas soaked with 0.5% Rf, threefold higher than those soaked with 0.1% Rf, and twofold higher than corneas soaked in BAK without epithelial debridement. Organ culture of treated corneas showed a normal corneal epithelium following FS machining while BAK-treated corneas showed extensive epithelial and stromal damage at 24 hours posttreatment. Conclusions: FS corneal epithelial machining can be used to enhance penetration of Rf into the stroma for corneal CXL. Translational Relevance: The creation of epithelial microchannels allows for stromal Rf concentrations high enough to perform true transepithelial crosslinking.

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Determining the efficacy of corneal crosslinking in progressive keratoconus

Cited by 10 publications

References 17 publications

Collagen fiber crimping following in vivo UVA-induced corneal crosslinking

Collagen fiber crimping following in vivo UVA-induced corneal crosslinking

Carissa opaca: A plant with great potential for future drugs for degenerative and infectious diseases

Enhanced Transepithelial Riboflavin Delivery Using Femtosecond Laser-Machined Epithelial Microchannels

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