Accelerated Pulsed High-Fluence Corneal Cross-Linking for Progressive Keratoconus

Gore, Daniel M.; Leucci, Marcello; Koay, Su-Yin; Kopsachilis, Nikolaos; Nicolae, Michael N.; Malandrakis, M.; Anand, Vijay; Allan, Bruce

doi:10.1016/j.ajo.2020.08.021

Cited by 23 publications

(17 citation statements)

References 36 publications

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“…A pulsed C-CXL approach with on and off cycles was recently conceptualized to allow recovery time for oxygen replenishment and hence increase its stromal availability. In a recent large prospective uncontrolled study conducted at the Moorfields Eye Hospital, Gore and colleagues 39 have reported keratometric stabilization in 98.3% of the 870 patients with an epi-off pulsed high-fluence protocol (30 mW/cm 2 for 4 minutes with 1.5 seconds on/off cycles) after 2 years of followup. In keeping with this finding, studies have shown deeper demarcation lines (a contested indicator of successful cross-linking) and more resistance to enzymatic digestion with pulsed protocols compared to continuous accelerated protocols.…”

Section: Advances In Treatmentmentioning

confidence: 99%

Advances in the diagnosis and treatment of keratoconus

2021

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Keratoconus had traditionally been considered a rare disease at a time when the imaging technology was inept in detecting subtle manifestations, resulting in more severe disease at presentation. The increased demand for refractive surgery in recent years also made it essential to more effectively detect keratoconus before attempting any ablative procedure. Consequently, the armamentarium of tools that can be used to diagnose and treat keratoconus has significantly expanded. The advances in imaging technology have allowed clinicians and researchers alike to visualize the cornea layer by layer looking for any early changes that might be indicative of keratoconus. In addition to the conventional geometrical evaluation, efforts are also underway to enable spatially resolved corneal biomechanical evaluation. Artificial intelligence has been exploited in a multitude of ways to enhance diagnostic efficiency and to guide treatment. As for treatment, corneal cross-linking treatment remains the mainstay preventive approach, yet the current main focus of research is on increasing oxygen availability and developing new strategies to improve riboflavin permeability during the procedure. Some new combined protocols are being proposed to simultaneously halt keratoconus progression and correct refractive error. Bowman layer transplantation and additive keratoplasty are newly emerging alternatives to conventional keratoplasty techniques that are used in keratoconus surgery. Advances in tissue engineering and regenerative therapy might bring new perspectives for treatment at the cellular level and hence obviate the need for invasive surgeries. In this review, we describe the advances in the diagnosis and treatment of keratoconus primarily focusing on newly emerging approaches and strategies.

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Section: Advances In Treatmentmentioning

confidence: 99%

Advances in the diagnosis and treatment of keratoconus

2021

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“…Gore et al studied an accelerated pulsed high-fluence protocol for progressive keratoconus on 756 eyes ( Gore et al, 2021 ). Corneas with thickness <375 μm were excluded.…”

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

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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“…57 Many studies have reported that pulsed ACXL results in a significantly deeper stromal demarcation line than continuous ACXL, [67][68][69][70] and that exposure to pulsed UVA can result in greater apoptotic effects and higher tissue damage than continuous delivery. 71,72 In a study by Said et 76 All the aforementioned procedures have involved delivery of a broad beam of irradiation to the surface of the cornea. However, early results suggest that greater efficacy may be achieved using topography-guided customized cross-linking (PiXL), in which high fluence cross-linking is performed in a customizable pattern with the intensity based on the patients' refractive error and corneal topography.…”

Section: Pulsed and Oxygen Supplemented Crosslinking Protocolsmentioning

confidence: 99%

Keratoconus: cross-linking the window of the eye

Hayes

Morgan

Meek

2021

Therapeutic Advances in Rare Disease

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Keratoconus is a condition in which the cornea progressively thins and weakens, leading to severe, irregular astigmatism and a significant reduction in quality of life. Although the precise cause of keratoconus is still not known, biochemical and structural studies indicate that overactive enzymes within the cornea break down the constituent proteins (collagen and proteoglycans) and cause the tissue to weaken. As the disease develops, collagen fibres slip past each other and are redistributed across the cornea, causing it to change shape. In recent years, it was discovered that the photochemical induction of cross-links within the corneal extracellular matrix, through the use of riboflavin and ultraviolet (UVA) light, could increase the strength and enzymatic resistance of the tissue and thereby halt keratoconus progression. Worldwide acceptance and use of riboflavin/UVA corneal cross-linking therapy for halting keratoconus progression has increased rapidly, in accordance with the growing body of evidence supporting its long-term effectiveness. This review focusses on the inception of riboflavin/UVA corneal cross-linking therapy for keratoconus, its clinical effectiveness and the latest scientific advances aimed at reducing patient treatment time, improving patient comfort and increasing patient eligibility for treatment. Plain language summary Review of current treatments using cross-linking to halt the progress of keratoconus Keratoconus is a disease in which the curved cornea, the transparent window at the front of the eye, weakens, bulges forward into a cone-shape and becomes thinner. This change of curvature means that light is not focussed onto the retina correctly and vision is progressively impaired. Traditionally, the effects of early keratoconus were alleviated by using glasses, specialist contact lenses, rings inserted into the cornea and in severe cases, by performing a corneal transplant. However, it was discovered that by inducing chemical bonds called cross-links within the cornea, the tissue could be strengthened and further thinning and shape changes prevented. The standard cross-linking procedure takes over an hour to perform and involves the removal of the cells at the front of the cornea, followed by the application of Vitamin B2 eye drops and low energy ultraviolet light (UVA) to create new cross-links within the tissue. Clinical trials have shown this standard procedure to be safe and effective at halting keratoconus progression. However, there are many treatment modifications currently under investigation that aim to reduce patient treatment time and increase comfort, such as accelerated cross-linking procedures and protocols that do not require removal of the surface cells. This review describes the different techniques being developed to carry out corneal cross-linking efficiently and painlessly, to halt keratoconus progression and avoid the need for expensive surgery.

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Accelerated Pulsed High-Fluence Corneal Cross-Linking for Progressive Keratoconus

Cited by 23 publications

References 36 publications

Advances in the diagnosis and treatment of keratoconus

Advances in the diagnosis and treatment of keratoconus

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

Keratoconus: cross-linking the window of the eye

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