A Review of Corneal Collagen Cross-linking – Current Trends in Practice Applications

Li Lim1, *, Elizabeth Wen Ling Lim2
1 MBBS (Singapore), MMed (Ophth), FRCS(Ed), FAMS (S'pore) Senior Consultant, Corneal and External Eye Disease Service, Singapore National Eye Centre, Singapore
2 Undergraduate medical student, Yong Loo Lin School of Medicine, National University of Singapore, Singapore



To review the literature on current applications of corneal collagen cross-linking (CXL).


A review of publications on corneal cross-linking was conducted. This included systemic reviews, randomized controlled clinical trials, cohort studies, case-controlled studies and case series. A summary of the publications is tabulated.


The original indication of riboflavin – ultraviolet-A (UVA) induced corneal collagen cross-linking is to arrest the progression of keratoconus. Studies show that it is effective in arresting the progression of keratoconus and LASIK keratectasia with the standard Dresden protocol (epithelium-off). There are also improvements in visual, keratometric and topographic measurements over time. Severe complications of cross-linking are rare. The epithelium-on techniques have less efficacy than the Dresden protocol. Accelerated protocols have variable results, with some studies reporting comparable outcomes to the Dresden protocol while other studies reporting less efficacious outcomes. Cross-linking combined with refractive procedures provide better visual outcome but long term studies are warranted. Cross-linking for the treatment of infective keratitis is a promising new treatment modality. Initial studies show that it is more effective for superficial rather than deep infections and for bacterial rather than fungal infections.


Corneal cross-linking is a procedure with an expanding list of indications from the treatment of corneal ectasias to infective keratitis. While the standard Dresden protocol is established as the gold standard treatment for progressive keratoconus, the more recent protocols may require further refinements, investigative and long-term studies.

Keywords: Cornea collagen cross-linking, LASIK ectasia, Keratoconus, Infective keratitis.

Abstract Information

Identifiers and Pagination:

Year: 2018
Volume: 12
Publisher Item Identifier: EA-TOOPHTJ-2018-HT1-266-6

Article History:

Received Date: 07/07/2017
Revision Received Date: 05/12/2017
Acceptance Date: 22/01/2018
Electronic publication date: 7/6/2018
Collection year: 2018

© 2018 Lim et al.

open-access license: This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International Public License (CC-BY 4.0), a copy of which is available at: (https://creativecommons.org/licenses/by/4.0/legalcode). This license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Correspondence: Address correspondence to this author at the Singapore National Eye Centre, 11 Third Hospital Avenue, Singapore 168751, Singapore; Tel: +6562277255; E-mail: lim.li@singhealth.com.sg