Corneal Collagen Cross-Linking Complications

Evangelista, Charisma B; Hatch, Kathryn M

doi:10.1080/08820538.2017.1353809

Cited by 41 publications

(38 citation statements)

References 47 publications

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“…CXL using classic Dresden's protocol with epithelium removal (conventional CXL) showed long-term efficacy of stabilization and improvement for KC. However, postoperative complications using standard epi-off protocol [2][3][4][5], such as corneal haze, sterile corneal infiltrates, recurrent erosion syndrome, have been reported and should be taken into consideration. To reduce the risk of postoperative complications, epithelium-on(epi-on) protocols assisted by iontophoretic delivery or transepithelial riboflavin were brought into sight and were considered by some researchers to be a better choice.…”

Section: Introductionmentioning

confidence: 99%

Transepithelial corneal cross-linking assisted by two continuous cycles of iontophoresis for progressive keratoconus in adults: retrospective 5-year analysis

Luo

Fang

et al. 2020

Graefes Arch Clin Exp Ophthalmol

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The aim of this study is to compare the long-term effects of transepithelial corneal crosslinking with two continuous cycles of iontophoresis (EI-CXL) and conventional corneal crosslinking (C-CXL) in adults with progressive keratoconus. Methods A retrospective analysis was conducted in adults who underwent C-CXL or EI-CXL between 2013 and 2015. Visual acuity, corneal tomography, anterior segment optical coherence tomography, in vivo corneal confocal microscopy (IVCM), and endothelial cell count (ECC) were performed preoperatively and 5 years postoperatively. Results Sixty-eight patients with a mean age of (24.3 ± 3.8) years were included, 34 for each group. After CXL, UCVA or BCVA remained stable, while the spherical diopter, cylinder diopter, spherical equivalent, and K max significantly decreased at 1, 2, and 3 years in both groups than baseline (P < 0.05). No significant differences were found in any refractive or tomographic parameters as well as the minimal corneal thickness between groups during follow-up. At 5 years, K max was slightly higher in EI-CXL group (58.16 ± 6.28) than that of C-CXL group (57.46 ± 4.98). At 3 and 5 years, the minimal corneal thickness in C-CXL group was still significantly lower than baseline (P < 0.05). IVCM demonstrated the demarcation zone at a mean depth of (302.0 ± 41.7) μm after C-CXL, and at (251.2 ± 28.1) μm after EI-CXL (P < 0.001). Keratocyte repopulation was detectable at all follow-up timepoint in both groups. Postoperative complications including progression were recorded in 6 patients (11.7%) after C-CXL and 3 patients (8.8%) after EI-CXL. ECC remained stable in both groups. Conclusion EI-CXL showed approximate efficacy with C-CXL in stabilizing progressive keratoconus in adults. EI-CXL has the potential to be a preferable transepithelial protocol. Keywords Progressive keratoconus. Iontophoresis. Transepithelial corneal crosslinking. Tomography. In vivo confocal scanning microscopy Key message Most previous data revealed inferior efficacy of transepithelial corneal crosslinking assisted by iontophoresis when compared to conventional corneal crosslinking. The limited riboflavin penetration into the corneal stroma is considered as one of the critical inadequacies of standard transepithelial iontophoresis. In this retrospective five-year analysis, no significant differences of the long-term refractive and visual outcome were found between conventional corneal crosslinking and transepithelial corneal crosslinking assisted by two continuous cycles of iontophoresis. Improved stromal penetration depth was achieved by two continuous cycles of iontophoresis.

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Section: Introductionmentioning

confidence: 99%

Transepithelial corneal cross-linking assisted by two continuous cycles of iontophoresis for progressive keratoconus in adults: retrospective 5-year analysis

Luo

Fang

et al. 2020

Graefes Arch Clin Exp Ophthalmol

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“… 36 Adverse events associated with crosslinking such as anterior keratocyte apoptosis, infection, corneal edema, corneal nerve damage, and stromal haze have been reported. 37 , 38 In addition to these postoperative complications, separate studies have also shown that mutations in stromal proteoglycans can lead to random space reductions between adjacent collagen fibrils; formation of larger, more variable collagen fibrils; and corneal opacity. 39 The transformation of keratocytes to activated fibroblasts and myofibroblasts while critical to corneal wound healing is known to be a major contributing factor in the development of corneal haze and fibrosis.…”

Section: Discussionmentioning

confidence: 99%

Intrastromal Injection of Hyaluronidase Alters the Structural and Biomechanical Properties of the Corneal Stroma

Kim

Jalilian

Thomasy

et al. 2020

Trans. Vis. Sci. Tech.

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Glycosaminoglycans (GAGs) are important components of the corneal stroma, and their spatiotemporal arrangement regulates the organization of collagen fibrils and maintains corneal transparency. This study was undertaken to determine the consequences of hyaluronidase (HAse) injected into the corneal stroma on stromal stiffness and ultrastructure. Methods: Equal volumes of HAse or balanced salt solution (vehicle) were injected intrastromally into the corneas of New Zealand white rabbits. Ophthalmic examination and multimodal imaging techniques, including Fourier-domain optical coherence tomography and in vivo confocal microscopy (IVCM), were performed at multiple time points to evaluate the impact of HAse treatment in vivo. Atomic force microscopy and transmission electron microscopy (TEM) were used to measure corneal stiffness and collagen's interfibrillar spacing, respectively. Results: Central corneal thickness progressively decreased after HAse injection, reaching its lowest value at day 7, and then returned to normal by day 42. The HAse did not impact the corneal endothelium but transiently altered keratocyte morphology at days 1 and 7, as measured by IVCM. HAse-injected corneas became stiffer by day 1 postinjection, were stiffest at day 7, and returned to preinjection values by day 90. Changes in stromal stiffness correlated with decreased interfibrillar spacing as measured by TEM. Conclusions: Degradation of GAGs by HAse decreases the corneal thickness and increases stromal stiffness through increased packing of the collagen fibrils in a timedependent manner. Translational Relevance: Intrastromal HAse injection appears relatively safe in the normal cornea, but its impact on corneal biomechanics and structure under pathologic conditions requires further study.

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“…The Dresden protocol overcame this through epithelial debridement (“epithelium-off”), allowing diffusion of riboflavin molecules into the stroma. Even though epithelial debridement provides favourable riboflavin penetration, this is associated with risks such as pain, infection, persistent epithelial defects, and corneal melt ( Spoerl et al, 2007 ; Evangelista and Hatch, 2018 ).…”

Section: Maximising Pharmacokinetic Properties Of Riboflavin/ultraviolet-a In the Treatment Of Keratoconusmentioning

confidence: 99%

“…The precise mechanism for herpes simplex virus reactivation after CXL remains unknown. It is postulated that emotional stress, trauma, and exposure to UVA are possible mechanisms of reactivation ( Evangelista and Hatch, 2018 ).…”

Section: Contraindications and Complicationsmentioning

confidence: 99%

Corneal Cross-Linking: The Evolution of Treatment for Corneal Diseases

Lim

et al. 2021

Front. Pharmacol.

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Corneal cross-linking (CXL) using riboflavin and ultraviolet A (UVA) light has become a useful treatment option for not only corneal ectasias, such as keratoconus, but also a number of other corneal diseases. Riboflavin is a photoactivated chromophore that plays an integral role in facilitating collagen crosslinking. Modifications to its formulation and administration have been proposed to overcome shortcomings of the original epithelium-off Dresden CXL protocol and increase its applicability across various clinical scenarios. Hypoosmolar riboflavin formulations have been used to artificially thicken thin corneas prior to cross-linking to mitigate safety concerns regarding the corneal endothelium, whereas hyperosmolar formulations have been used to reduce corneal oedema when treating bullous keratopathy. Transepithelial protocols incorporate supplementary topical medications such as tetracaine, benzalkonium chloride, ethylenediaminetetraacetic acid and trometamol to disrupt the corneal epithelium and improve corneal penetration of riboflavin. Further assistive techniques include use of iontophoresis and other wearable adjuncts to facilitate epithelium-on riboflavin administration. Recent advances include, Photoactivated Chromophore for Keratitis-Corneal Cross-linking (PACK-CXL) for treatment of infectious keratitis, customised protocols (CurV) utilising riboflavin coupled with customised UVA shapes to induce targeted stiffening have further induced interest in the field. This review aims to examine the latest advances in riboflavin and UVA administration, and their efficacy and safety in treating a range of corneal diseases. With such diverse riboflavin delivery options, CXL is well primed to complement the armamentarium of therapeutic options available for the treatment of a variety of corneal diseases.

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Corneal Collagen Cross-Linking Complications

Cited by 41 publications

References 47 publications

Transepithelial corneal cross-linking assisted by two continuous cycles of iontophoresis for progressive keratoconus in adults: retrospective 5-year analysis

Transepithelial corneal cross-linking assisted by two continuous cycles of iontophoresis for progressive keratoconus in adults: retrospective 5-year analysis

Intrastromal Injection of Hyaluronidase Alters the Structural and Biomechanical Properties of the Corneal Stroma

Corneal Cross-Linking: The Evolution of Treatment for Corneal Diseases

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