Interface Bonding With Corneal Crosslinking (CXL) After LASIK Ex Vivo

Seiler, Theo; Engler, Marleen; Beck, Eric; Birngruber, Reginald; Kochevar, Irene E.

doi:10.1167/iovs.17-22426

Cited by 10 publications

(13 citation statements)

References 28 publications

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“…The same oxygen deprived conditions also apply to any deeper lamellar approaches within the cornea, including corneal incisions 9 and laser-assisted in situ keratomileusis (LASIK) flaps. 4 Because in a clinical setting the cornea will likely never be fully deprived of oxygen, some of the crosslinking must be attributed to the singlet oxygen pathway. However, as described previously, the oxygen dependent (singlet oxygen) and oxygen-independent pathways produce are complementary and produce equivalent crosslinking.…”

Section: Discussionmentioning

confidence: 99%

“…Photosensitized protein crosslinking using rose bengal (RB) and green light at 532 nm (RB CXL) has several demonstrated applications in the cornea, including stromal stiffening for treatment of ectatic diseases, such as keratoconus, photobonding of LASIK flaps to the corneal stroma, and sealing wounds and lacerations in preclinical studies. [1][2][3][4][5] Recently, the first uses of RB photosensitization in a human patient's cornea was reported. [6][7][8] The treatment halted a sightthreatening case of fusarium keratitis and, 16 months later, the cornea showed a persistent demarcation line in optical coherence tomography (OCT), a classical sign of corneal crosslinking.…”

Section: Introductionmentioning

confidence: 99%

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Arginine as an Enhancer in Rose Bengal Photosensitized Corneal Crosslinking

Wertheimer

Mendes

Pei

et al. 2020

Trans. Vis. Sci. Tech.

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Oxygen-independent cornea crosslinking (CXL) using rose bengal (RB) and green light may have unique clinical applications. These studies were designed to gain insight into the arginine (arg)-enhanced anaerobic crosslinking process, to maximize crosslinking efficiency, and to test a clinically feasible method for oxygen-free CXL. Methods: Rabbit corneas were treated ex vivo using 1 mM RB and 532 nm light. RB photodecomposition, monitored by absorption spectrophotometry, was used to optimize arg concentration and to develop an irradiation and re-dying protocol. The minimal effective green light fluence was identified by linear tensile strength measurements. RB penetration into the stroma was determined by fluorescence microscopy. To favor the anaerobic pathway, a contact lens was used to minimize stromal oxygen level during irradiation. Stromal cell toxicity was evaluated by a terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) assay. Results: RB photodecomposition reached 75% of its maximal effect at 200 mM arg and the optimal fluence increment was 32.7 J/cm 2. The minimal effective fluence for cornea stiffening was 65.4 J/cm 2. Placement of a contact lens promoted oxygen-independent cornea stiffening, similar to that obtained on isolated, oxygen-deprived cornea. RB penetration into the stroma with arg present was limited to ∼120 μm, about 25% deeper than without arg. Stromal cell toxicity was limited to the depth of RB and arg penetration. Conclusions: An oxygen-independent pathway in cornea for RB-CXL was characterized and optimized, including a possible clinical protocol for its use. Translational Relevance: Oxygen-independent RB-CXL is an efficient and effective process that can be developed further for unique clinical applications.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Arginine as an Enhancer in Rose Bengal Photosensitized Corneal Crosslinking

Wertheimer

Mendes

Pei

et al. 2020

Trans. Vis. Sci. Tech.

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“…As there are reports of flap displacements happening up to 14 years [6] and flap re-lifts happening up to 18 years [9] after LASIK, there seems to remain a reduced adhesion of the flap over a long period. Additional corneal crosslinking after LASIK, which demonstrably increases the interface bonding [10], is yet not very popular due to potential side effects [11], extended operating time, and costs. Besides, traumatic flap dislocations are a very rare and unpredictable event, therefore, it remains questionable whether general treatment in all cases is justified to possibly prevent accidental traumatic dislocations.…”

Section: Discussionmentioning

confidence: 99%

Calzone-Like Traumatic Flap Dislocation Four Years after Laser in situ Keratomileusis

Fischinger¹,

Wendelstein

Bolz

et al. 2019

Case Rep Ophthalmol

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A 46-year-old patient presented with a flip-folded partially dislocated flap after trauma caused by a sheet of paper, four years after a reportedly uneventful laser in situ keratomileusis procedure using microkeratome. Flap re-lift, mechanical debridement, and flap stretching were performed in a first interventional approach. Due to epithelial ingrowth two month after the first intervention, a flap re-lift and mechanical removal of epithelial cells from the stroma bed and flap were performed. In addition, triamcinolone was applied subconjunctivally. Thereafter, best corrected visual acuity of 20/20 was regained and no more epithelial ingrowth was observed. Only few cases of flap dislocation with epithelial ingrowth have been described in the literature following trauma, though none of a permanently inward folded flap. The use of subconjunctival triamcinolone is a new approach to prevent recurrent epithelial ingrowth.

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“…This treatment also appeared to bond the LASIK flap to the stroma. A recent study tested the hypothesis that immediate bonding is produced between the LASIK flap and stroma by photosensitized protein crosslinking and identified optimized treatment parameters . In an ex vivo study, both photosensitizers increased by two‐fold the adhesion between flap and stroma as determined by shear stress testing.…”

Section: Clinical Applications Of Photochemical Crosslinkingmentioning

confidence: 99%

Medical Applications of Rose Bengal‐ and Riboflavin‐Photosensitized Protein Crosslinking

Redmond

Kochevar

2019

Photochem & Photobiology

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This review summarizes research on many of the potential applications of photosensitized crosslinking of tissue proteins in surgery and current knowledge of the photochemical mechanisms underlying formation of the covalent protein–protein crosslinks involved. Initially developed to close wounds or reattach tissues, protein photocrosslinking has also been demonstrated to stiffen and strengthen tissues, decrease inflammatory responses and facilitate tissue bioengineering. These treatments appear to result largely from crosslinks within and between collagen molecules in tissue that typically form by an oxygen‐dependent mechanism. Surgical applications discussed include sealing wounds in skin, cornea and bowel; reattaching severed nerves, blood vessels and tendons; strengthening cornea and vein; reducing capsular contracture after breast implants; and regenerating joint cartilage.

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Interface Bonding With Corneal Crosslinking (CXL) After LASIK Ex Vivo

Abstract: Based on ex-vivo results, interface bonding after LASIK using crosslinking with either rose bengal or riboflavin increases the adhesion between flap and stromal bed. In vivo trials are needed to evaluate the temporal evolution of the effect.

Cited by 10 publications

References 28 publications

Arginine as an Enhancer in Rose Bengal Photosensitized Corneal Crosslinking

Arginine as an Enhancer in Rose Bengal Photosensitized Corneal Crosslinking

Calzone-Like Traumatic Flap Dislocation Four Years after Laser in situ Keratomileusis

Medical Applications of Rose Bengal‐ and Riboflavin‐Photosensitized Protein Crosslinking

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