Corneal collagen crosslinking (CXL) was first described in 1997 by Spoerl et al.
4 It has been subsequently used for many years as a means of stabilizing ectatic corneas in keratoconus and iatrogenic corneal ectasia. In this procedure, covalent bonds are created between amino groups within the collagen molecules or between proteoglycan core proteins and collagen to make the anterior corneal stroma more rigid.
5 Riboflavin, which acts as a photosensitizer in the crosslinking reaction, is applied topically to the cornea and allowed to penetrate into the corneal stroma. Ultraviolet-A (UVA) light is then used to excite the riboflavin, causing it to interact with molecular bonds in the collagen fibers, and inducing them to crosslink, which enhances the diameter and rigidity of the fibers.
6,7 A more recent study has also demonstrated that riboflavin–UVA crosslinks most likely also occur within proteoglycan core proteins and between proteoglycan core proteins attached to an individual fibril or adjacent fibrils.
8 Over the years, numerous studies have observed anterior corneal flattening in cases of corneal ectasia treated with CXL.
9–11 An improved understanding of CXL has subsequently led to the theorization that CXL could also be used in healthy corneas to produce a predictable and reproducible alteration in corneal shape and be used to treat myopia, hyperopia, and astigmatism. The original idea of using CXL for primary refractive correction originated based on the findings of Hersh et al.
12 in 2011 that both uncorrected distance visual acuity and corrected distance visual acuity had significantly improved at 1 year in eyes that had undergone CXL in keratoconus or corneal ectasia patients. In 2011, Sinha Roy and Dupps
13 also provided a proof of concept of patient-specific differential refractive responses to CXL. Using three-dimensional finite element models, they showed that smaller, focal, cone-centered CXL simulations provided the greatest topographic effects.
13 In 2016, Seiler et al.
14 performed a clinical study comparing the efficacy of customized CXL with standard CXL. The authors found that the ΔK
max was greater in the customized CXL group. Shetty et al.
15 also compared the effect of four different customized CXL methods in keratoconic eyes. In this study, the authors found that a ring tangential map protocol provided the greatest decrease in curvature (
P < 0.05) and greatest improvement in uncorrected visual acuity and corrected distance visual acuity per unit energy dose to the cornea (
P > 0.05), compared with a uniform treatment, a sector axial map protocol, and a ring axial map protocol. Brooks et al.
16 also suggested that patients experience subjective improvement in visual function after undergoing CXL for keratoconus and corneal ectasia. In 2013, Park and Chuck
17 reexamined the effect of CXL in mild post-LASIK ectasia, based on a study by Celik et al.
18 The authors found a difference in the mean spherical equivalent between the control group and the LASIK-CXL of –0.53 ± 0.22 as motivation for further consideration of CXL for myopia correction.