Epithelium-Off Corneal Crosslinking Has Low Risk of Early Complications

Laser eye surgery
Laser eye surgery. Close-up of the eye of a patient undergoing LASIK eye surgery. LASIK (laser-assisted in-situ keratomileusis) is a type of refractive laser eye surgery that corrects a condition called astigmatism. A laser is used to correct blurred vision caused by an irregular curvature of the cornea or lens. It is also used to correct myopia (short-sightedness) and hyperopia (long-sightedness). The outer layer of the cornea has been cut open and a flap (right) pulled open. The laser is then used to reshape the stroma, the middle layer of the cornea.
Delaying procedure could lead to delayed further keratoconus progression and increased economic burdens, according to investigators.

Corneal crosslinking (CXL) for keratoconus and post-refractive keratectasia using the current US Food & Drug Administration (FDA)-approved “epithelium-off (epi-off)” protocol appears to be safe with a low risk of postoperative complications, according to research published in Clinical Ophthalmology.

Researchers conducted a multicenter, retrospective cohort study of patients who underwent epi-off CXL for keratoconus and postrefractive keratectasia system between 2016 and 2018 to evaluate the occurrence of early postoperative complications. In particular, the team reviewed incidence of including delayed epithelial healing, infection, and loss of visual acuity, following the FDA-approved clinical protocol for the procedure.

A total of 878 eyes of 654 patients (mean age, 27 years; range, 7-71; 66% men and 34% women) were included in the study. Most patients (91.6%) had keratoconus, while the rest (8.4%) had postrefractive corneal ectasia. Follow up duration was 1 year for 44% of eyes, 6 months for 27.7% of eyes, 3 months for 18.7% of eyes, and 1 month for 10.1% of eyes.

Prolonged follow up was necessary for 5% of eyes due to the occurrence of complications in the early post-operative period. Among these eyes, the rates of delayed epithelial healing and keratitis were 3.9% (95% confidence interval [CI], 2.7-5.3%) and 1.5% (95% CI, 0.8-2.5%), respectively. 

Delayed epithelial healing was managed using 4 treatment modalities: repeat bandage contact lens (BCL), continued routine care, pressure patch, and antibiotic ointment. The researchers found that epithelium healing duration was the longest in eyes treated with BCL (23.8 days) and shortest in those treated with antibiotic ointment (14.3 days; P <.05).

“The concern for early clinical complications after epi-off CXL often leads to delayed CXL intervention and further keratoconus progression with increased economic burdens,” researchers report. “[This] large retrospective review of 878 eyes found that FDA-approved epi-off CXL protocol appears to be safe with low occurrence rates of early post-operative complications.” 

The team recommended the use of antibiotic ophthalmic ointment for the management of delayed epithelial healing.

The primary limitations of the study included the retrospective design and short-term follow up; lack of measurement of epithelial defect size; and numerous surgeons across sites conducted the surgeries.


Ang MJ, Darbinian JA, Hoskins EN, Holsclaw DS, Sudesh S, Chandra NS. The safety profile of FDA-approved epithelium-off corneal cross-linking in a US community-based healthcare system. Clin Ophthalmol. 2022;16:1117-1125. doi:10.2147/OPTH.S359224