Customized Crosslinking Plus Supplemental Oxygen Improves Postoperative Outcomes

Researchers investigate the use of a customized corneal crosslinking approach that employs a transepithelial approach with supplemental oxygen to treat of progressive keratoconus.

Customized corneal crosslinking (CXL) via a transepithelial approach that incorporates supplemental intraoperative oxygen leads to clinically meaningful improvements in both corneal curvature and corrected distance visual acuity (CDVA) in patients with progressive keratoconus. 

In a study published in the Journal of Cataract and Retinal Surgery, researchers report on first experiences with epithelium-on, customized CXL with intraoperative supplemental oxygen for progressive keratoconus management. Included patients had a progressive keratoconus diagnosis of stage I or stage II and minimum optical corneal pachymetry ≥450 µm. The primary outcome measures included CDVA, corneal tomography, demarcation line detection at postoperative month 1, and endothelial cell count via corneal specular microscopy. 

The total study population included 27 eyes from 24 patients (14 men; mean age, 29.3±7.3 years) with mild-to-moderate keratoconus. Participants underwent customized corneal CXL with a transepithelial approach; ultraviolet-A irradiation (365 nm wavelength) was delivered in a 2-zone elliptical pattern. Total dose delivered was 10 J/cm2 at the keratoconus apex. 

At the 6-month postoperative follow up, both mean uncorrected distance visual acuity (UCVA) and CDVA improved significantly from baseline (0.26 ± 0.05 to 0.19 ± 0.07 and 0.19 ± 0.06 to 0.11 ± 0.05 logarithm of the minimum angle of resolution, respectively; P <.05). No significant changes in refractive parameters or significant reductions in tomographic or subjective cylinder were noted in this timeframe. 

Significant flattening of steep keratometry was noted, with a mean change of -1.9 D (P <.05). No significant changes in pachymetry were observed at the 6-month follow up, although investigators did identify a nonsignificant trend towards reduction from mean preoperative minimum pachymetry (472.66 µm ± 21 µm to 464.71 µm ± 24.38 µm). Corneal higher-order aberrations (HOAs) — in particular, coma and vertical trefoil — demonstrated significant 6-month improvement. 

Finally, endothelial cell density did not demonstrate a statistically significant reduction from mean baseline cell count (2522 cells/mm2 ± 33 cells/mm2 to 2489 cells/mm2 ± 29 cells/mm2). At the 1-month postoperative evaluation, a double demarcation line was identified via anterior segment OCT; mean depth was 218.23 µm ± 43.22 µm in the corneal area (treated at 7.2 J/cm2 fluence) and 325.71 µm ± 39.70 µm in the steeper corneal area. In 1 eye, no demarcation line was visible, while in 3 eyes, the line was visible only in the steeper area (mean depth, 218 µm ± 18.02 µm). 

“The preliminary results of this pilot study demonstrate the potential for epi-on, CXL with supplemental oxygen to reduce corneal HOAs and reduce corneal curvature in patients with progressive [keratoconus],” the researchers concluded. “The results of our study compared favorably with previous reports of epi-off customized CXL.” 

They added that although longer-term follow-up studies inclusive of a larger patient cohort are necessary, “the outcomes of this study suggest that high-irradiance epi-on customized CXL with supplemental oxygen might be a promising alternative to S-CXL in patients with progressive [keratoconus] with the potential to improve visual outcomes and reduce complications.” 


Mazzotta C, Sgheri A, Bagaglia SA, Rechichi M, Di Maggio A. Customized corneal crosslinking for treatment of progressive keratoconus: Clinical and OCT outcomes using a transepithelial approach with supplemental oxygen. J Cataract Refract Surg. 2020;46(12):1582-1587.