Riboflavin/ultraviolet-a–induced collagen crosslinking for the treatment of keratoconus

Wollensak, Gregor; Spoerl, Eberhard; Seiler, Theo

doi:10.1016/s0002-9394(02)02220-1

Cited by 2,518 publications

(2,499 citation statements)

References 28 publications

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“…Thus the collagenases from bacteria, digest the human collagen causing the cornea to melt. Moreover, collagen cross linking is a useful technique which uses riboflavin and UVA irradiation to strengthen corneal tissues thereby enhancing its rigidity [175,176,208]. The interaction between riboflavin and UVA strengthens chemical bond formation between collagen fibrils and hence increasing its resistance to enzy matic digestion [177].…”

Section: Treatmentmentioning

confidence: 99%

Pathogenesis of microbial keratitis

Lakhundi

Siddiqui

Khan

2017

Microbial Pathogenesis

168

121

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Microbial keratitis is a sight-threatening ocular infection caused by bacteria, fungi, and protist pathogens. Epithelial defects and injuries are key predisposing factors making the eye susceptible to corneal pathogens. Among bacterial pathogens, the most common agents responsible for keratitis include Staphylococcus aureus, Pseudomonas aeruginosa, Streptococcus pneumonia and Serratia species. Fungal agents of corneal infections include both filamentous as well as yeast, including Fusarium, Aspergillus, Phaeohyphomycetes, Curvularia, Paecilomyces, Scedosporium and Candida species, while in protists, Acanthamoeba spp. are responsible for causing ocular disease. Clinical features include redness, pain, tearing, blur vision and inflammation but symptoms vary depending on the causative agent. The underlying molecular mechanisms associated with microbial pathogenesis include virulence factors as well as the host factors that aid in the progression of keratitis, resulting in damage to the ocular tissue. The treatment therefore should focus not only on the elimination of the culprit but also on the neutralization of virulence factors to minimize the damage, in addition to repairing the damaged tissue. A complete understanding of the pathogenesis of microbial keratitis will lead to the rational development of therapeutic interventions. This is a timely review of our current understanding of the advances made in this field in a comprehensible manner. Coupled with the recently available genome sequence information and high throughput genomics technology, and the availability of innovative approaches, this will stimulate interest in this field.

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Section: Treatmentmentioning

confidence: 99%

Pathogenesis of microbial keratitis

Lakhundi

Siddiqui

Khan

2017

Microbial Pathogenesis

168

121

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“…1 A variety of options have been described for the management of this pathologic condition, such as rigid gas-permeable contact lenses, 2 corneal collagen cross-linking, 3 intracorneal ring segment implantation, [4][5][6][7][8][9][10][11] or keratoplasty. 12 In a number of studies intracorneal ring segments (ICRS) have been demonstrated to be effective in improving visual acuity and reducing the refractive error and the mean keratometry in selected cases of keratoconic eyes.…”

Section: K Eratoconus Is An Ectatic Debilitatingmentioning

confidence: 99%

Outcome Analysis of Intracorneal Ring Segments for the Treatment of Keratoconus Based on Visual, Refractive, and Aberrometric Impairment

Vega-Estrada

Alió

Brenner

et al. 2013

American Journal of Ophthalmology

115

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PURPOSE: To analyze the outcomes of intracorneal ring segment (ICRS) implantation for the treatment of keratoconus based on preoperative visual impairment. DESIGN: Multicenter, retrospective, nonrandomized study.METHODS: A total of 611 eyes of 361 keratoconic patients were evaluated. Subjects were classified according to their preoperative corrected distance visual acuity (CDVA) into 5 different groups: grade I, CDVA of 0.90 or better; grade II, CDVA equal to or better than 0.60 and worse than 0.90; grade III, CDVA equal to or better than 0.40 and worse than 0.60; grade IV, CDVA equal to or better than 0.20 and worse than 0.40; and grade plus, CDVA worse than 0.20. Success and failure indices were defined based on visual, refractive, corneal topographic, and aberrometric data and evaluated in each group 6 months after ICRS implantation.RESULTS: Significant improvement after the procedure was observed regarding uncorrected distance visual acuity in all grades (P < .05). CDVA significantly decreased in grade I (P < .01) but significantly increased in all other grades (P < .05). A total of 37.9% of patients with preoperative CDVA 0.6 or better gained 1 or more lines of CDVA, whereas 82.8% of patients with preoperative CDVA 0.4 or worse gained 1 or more lines of CDVA (P < .01). Spherical equivalent and keratometry readings showed a significant reduction in all grades (P £ .02). Corneal higher-order aberrations did not change after the procedure (P ‡ .05).CONCLUSIONS: Based on preoperative visual impairment, ICRS implantation provides significantly better results in patients with a severe form of the disease. K ERATOCONUS IS AN ECTATIC DEBILITATING corneal disorder characterized by a progressive corneal thinning that results in corneal protrusion, irregular astigmatism, and decreased vision. 1 A variety of options have been described for the management of this pathologic condition, such as rigid gas-permeable contact lenses, 2 corneal collagen cross-linking, 3 intracorneal ring segment implantation, 4-11 or keratoplasty. 12 In a number of studies intracorneal ring segments (ICRS) have been demonstrated to be effective in improving visual acuity and reducing the refractive error and the mean keratometry in selected cases of keratoconic eyes. 4-11 Such a positive therapeutic effect is considered to be based on the induction of a remodeling of the corneal anterior and posterior surface's topography, which improves the optical quality of the cornea and reduces the optical aberrations, with consequent improvement in best-corrected visual acuity. [4][5][6][7][8][9][10][11] Although in the healthy cornea, the sectorial arcuate addition to the corneal local volume caused by these implants at the corneal midperiphery induces a flattening of the central cornea in an arc-shortening effect, with the consequence of a decrease in myopic spherical equivalent attributable to the overall reduction in the optical power of the cornea, 13 such corneal modeling effect may be different in structurally abnormal corneas such as in keratoco...

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“…CXL with riboflavin application and ultraviolet (UV)A irradiation is a novel treatment for corneal ectatic diseases 18. CXL has been used for the treatment of progressive keratoconus since 2003 and received US Food and Drug Administration approval in 2016 19. In addition, this CXL method is also used in corneal ulcers, pellucid marginal degeneration, corneal melting, and iatrogenic keratectasia after laser eye surgery 20.…”

Section: Introductionmentioning

confidence: 99%

UV light crosslinking regresses mature corneal blood and lymphatic vessels and promotes subsequent high-risk corneal transplant survival

Hou

Tóth

et al. 2018

American Journal of Transplantation

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Immunologic graft rejection is the main complication after corneal transplant into pathologically prevascularized so‐called high‐risk eyes. The aim of this study was to evaluate whether ultraviolet (UV) light crosslinking can regress pathologic corneal blood and lymphatic vessels and thereby improve subsequent graft survival. Using the murine model of suture‐induced corneal neovascularization, we found that corneal crosslinking with UVA light and riboflavin regressed both preexisting blood and lymphatic vessels significantly via induction of apoptosis in vascular endothelial cells. In addition, macrophages and CD45+ cell counts were significantly reduced. Consistently, corneal crosslinking reduced keratocyte density and corneal thickness without affecting corneal nonvascular endothelial cells, iris, and lens depending on the crosslinking duration. Furthermore, using the murine model of corneal transplant, long‐term graft survival was significantly promoted (P < .05) and CD4+ CD25+FoxP3+ T regulatory cells were upregulated (P < .01) in high‐risk eyes preoperatively treated with crosslinking. Our results suggest UV light crosslinking as a novel method to regress both pathologic corneal blood and lymphatic vessels and to reduce CD45+ inflammatory cells. Furthermore, this study demonstrates for the first time that preoperative corneal crosslinking in prevascularized high‐risk eyes can significantly improve subsequent graft survival and may become a promising novel therapy in the clinic.

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Riboflavin/ultraviolet-a–induced collagen crosslinking for the treatment of keratoconus

Cited by 2,518 publications

References 28 publications

Pathogenesis of microbial keratitis

Pathogenesis of microbial keratitis

Outcome Analysis of Intracorneal Ring Segments for the Treatment of Keratoconus Based on Visual, Refractive, and Aberrometric Impairment

UV light crosslinking regresses mature corneal blood and lymphatic vessels and promotes subsequent high-risk corneal transplant survival

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