Post-FDA Approval Results of Epithelium-Off, Full-Fluence, Dresden Protocol Corneal Collagen Crosslinking in the USA

Abstract

Introduction: The purpose of this non-comparative, prospective, observational study was to evaluate the post-US Food and Drug Administration approval outcomes of epithelium-off, full-fluence, Dresden protocol corneal collagen crosslinking (CXL) for the treatment of progressive keratoconus (KCN) and post-refractive corneal ectasia at a US academic tertiary medical center. Methods: This study involved 125 eyes of 97 patients with KCN and 13 eyes of 12 patients with post-refractive ectasia which underwent CXL between November 2016 and September 2019. Best spectacle-corrected visual acuity (BSCVA) and corneal topographic parameters were measured preoperatively, at postoperative month 1 (POM-1), and between postoperative months 3 and 24 (POM 3-24). Results: Best spectacle-corrected visual acuity, flat keratometry, steep keratometry, and mean corneal power worsened at POM-1 (p \ 0.01) with a return to preoperative values at POM 3-24. Maximum keratometry (Kmax) steepened at POM-1 and then improved beyond preoperative levels at POM 3-24 (p \ 0.01 and p = 0.03, respectively). Pachymetry at the apex and pupil decreased at POM-1 and POM 3-24 (p = 0.03). Pachymetry at the thinnest point decreased at POM-1 and trended toward reduction at POM 3-24 (p \ 0.001 and p = 0.06, respectively). Visual and tomographic outcomes were similar between pediatric and adult populations, and between KCN and post-refractive ectasia patients. Conclusions: Real-world results of CXL in the USA are similar to those reported in prior studies, demonstrating an initial worsening of BSCVA, pachymetry, and keratometry followed by corneal flattening and preservation of visual acuity. Improvements in Kmax and stability in visual acuity were observed over 24 months in children and adults with progressive KCN or post-refractive ectasia.

Independent-effect comparison of five crosslinking procedures for Progressive Keratoconus based on Keratometry and the ABCD Grading System using Generalized Estimating Equations (GEE)

“…A prior study reported that pediatric central and paracentral corneal thicknesses increase slowly but did not elaborate on the reason for this phenomenon [ 37 ]. However, MCT changes did not significantly differ between adult and pediatric patients at 2 and 4 years after CXL [ 38 , 39 ]. A longer term follow-up is therefore needed to validate this finding.…”

Crosslinking vs. Observation in Fellow Eyes of Keratoconus Patients

“…Currently, epithelium-off CXL is the only FDA-approved treatment that has been reported to slow or halt the progression of KC in its early to moderate stages, with numerous studies supporting its efficacy [ 7 , 8 , 11 ]. A previous study of bilateral sequential CXL versus delayed CXL demonstrated progression in 27% of the patients in the delayed group, and an economical analysis for the office visits saved showed that immediate CXL may be a less costly approach than delayed CXL [ 10 ].…”

“…All subjects gave informed consent to participate in this study. A patient registry was compiled consisting of a cohort of 104 subjects with KC that initially underwent unilateral epithelium-off, using the Dresden protocol CXL, in the worse eye, between November 2016 and July 2019 as described in our previous study [ 11 ]. Of the 104 subjects, 12 eyes with laser-assisted in situ keratomileusis (LASIK)-induced ectasia and 12 subjects with a follow-up of less than six months were excluded from this analysis.…”

“…The criteria for performing CXL were as described in our previous study [ 11 ]. Briefly, these criteria consisted of progressive disease as defined by an increase in Kmax or steep keratometry (K2) based on Pentacam (OCULUS, Arlington, WA, USA) tomographical parameters of ≥1.0 D over ≤12 months.…”

Outcomes After Corneal Crosslinking for Keratoconus in Children and Young Adults

“…[3][4][5] A recent US study assessing the effects of epitheliumoff crosslinking in both keratoconus and postrefractive ectasia in 39 pediatric eyes demonstrated improvement in maximum keratometry (Kmax) and stability in visual acuity over 24 months. 6 Long-term outcomes outside the United States after crosslinking for pediatric keratoconus have also been promising. Mazzotta et al 7 assessed 62 eyes of 47 patients younger than 18 years with progressive keratoconus and showed that both uncorrected and corrected distance visual acuity (CDVA) were significantly improved in most eyes after 10 years.…”