Collagen Crosslinking for Postrefractive Ectasia

Key Concepts

Corneal collagen crosslinking (CXL) is a treatment designed to decrease the progression of keratoconus and postrefractive ectasia.
Maximum keratometry generally stabilizes and flattens, on average, by approximately 1.6 and 0.7 D after CXL for keratoconus and ectasia, respectively.
Average best corrected visual acuity significantly improves by approximately 1 Snellen line.
After CXL, clinical outcomes appear to worsen at 1 month and then improve between 3 months and 1 year.
Similar to the time course of clinical outcomes after CXL, there appears to be an increase in CXL-associated corneal haze, which peaks at 1 month, plateaus between 1 and 3 months, and improves between 3 months and 1 year.
In the future, faster and more precisely guided UV light delivery systems, as well as new forms of riboflavin and delivery techniques, may continue to improve the safety and efficacy of this new procedure.

Introduction

Corneal collagen crosslinking (CXL) is a treatment designed to decrease the progression of keratoconus, in particular, and other corneal thinning processes such as corneal ectasia after refractive surgery. Additionally, studies have suggested that CXL can also have beneficial visual and optical effects in some patients, such as an improvement in corneal steepness, visual acuity, topography irregularity indices, higher order aberrations, and subjective visual function.

Pathophysiology

Currently, while the pathogenesis of postrefractive surgery ectasia remains unclear, an understanding of corneal biomechanics may help to elucidate its pathophysiology. The cornea is a viscoelastic structure with both viscous and elastic components. In response to stress, there is an immediate elastic response of the cornea followed by a prolonged, time-dependent, viscoelastic recovery. Similar to keratoconus, it appears that there is a loss and/or slippage of collagen fibrils and changes to the extracellular matrix in the corneal stroma. These changes are thought to cause biomechanical instability of the corneal stroma with consequent changes in both the cornea’s anatomic and topographic architecture. In postrefractive ectasia it remains unclear whether these changes are concentrated in the posterior stroma, the residual stromal bed, or in the laser in situ keratomileusis (LASIK) flap itself. Furthermore, similar to keratoconus, ocular allergy and, specifically, eye rubbing may play a role in the development of postrefractive ectasia.

In the CXL procedure, riboflavin (vitamin B2) is administered in conjunction with ultraviolet A (UVA – 370 nm) irradiation. Riboflavin acts as a photosensitizer. The reactive oxygen species (singlet oxygen) produced by this interaction as well as UVA-excited molecules of riboflavin result in the crosslinking effect and causes mechanical stiffening of the cornea. Most of this “crosslinking” occurs within the collagen molecules themselves and the corneal proteoglycan matrix. Whether there are actual “crosslinks” between collagen fibers remains unclear; however, these are unlikely given the distances between the actual fibers. Independent of UVA light penetration, the interwoven collagen fibrils in the anterior stroma, compared to the posterior stroma, appear to enhance the stiffening effect of CXL as well. ^,

The Crosslinking Procedure

The procedure for the US multicenter collagen CXL trial was based on the original corneal CXL procedure described by Seiler and colleagues. In brief, a topical anesthetic is administered and the central 9 mm epithelium is removed by mechanical debridement. Riboflavin (0.1% riboflavin ophthalmic solution/20% dextran) is then administered topically every two minutes for a total of 30 minutes. Following riboflavin administration, riboflavin absorption is confirmed on slit lamp examination. At this time, pachymetry measurements are performed and if the cornea is <400 μm, hypotonic riboflavin (0.1% riboflavin ophthalmic solution) is administered, one drop every 10 seconds for 2 minute sessions, after which pachymetry measurements are performed again to confirm that the stroma has swelled to ≥400 μm. The goal of this is to provide adequate corneal thickness to absorb the incoming UV light to protect the endothelium from damage by the UV-riboflavin interaction. The cornea is aligned and then exposed to UVA 365 nm light for 30 minutes at an irradiance of 3.0 mW/cm ² . While the cornea is exposed to UVA light, riboflavin administration is continued every 2 minutes. Postoperatively, antibiotic and corticosteroid drops are administered, a soft contact lens bandage is placed, and the eye is reexamined by slit lamp examination. The contact lens is then removed after the epithelial defect is closed.

Clinical Outcomes

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