Pain mechanisms and management in corneal cross-linking: a review

Emilie Sophie van der Valk Bouman, Heather Pump, David Borsook, Boris Severinsky, Robert Pl Wisse, Hajirah N Saeed, Eric A Moulton, Emilie Sophie van der Valk Bouman, Heather Pump, David Borsook, Boris Severinsky, Robert Pl Wisse, Hajirah N Saeed, Eric A Moulton

Abstract

Though corneal collagen cross-linking (CXL) is an increasingly available and effective treatment for keratoconus, few reports have considered its impact on pain-related physiology in depth. This comprehensive narrative review summarises mechanisms underlying pain in CXL and clinical care possibilities, with the goal of future improvement in management of CXL-related pain. Postoperative pain associated with CXL is largely due to primary afferent nerve injury and, to a smaller extent, inflammation. Chronification of pain after CXL has not been reported, even as long-term nerve damage without regeneration following standard CXL treatment is frequently observed. The lack of pain chronification may be due to the minimally invasive nature of the procedure, with its rapidly recovering superficial corneal wound, and to the positive anti-inflammatory changes of the tear film that have been described after CXL. Different CXL approaches have been developed, with the transepithelial epithelial-on technique (epi-on) associated with less postsurgical pain than the gold standard, epithelial-off technique (epi-off). After the first few days, however, the difference in pain scores and need for analgesics between epi-on and epi-off disappear. Patients experience relatively high-intensity pain the first few days post-CXL, and many strategies for acute pain control following CXL have been studied. Currently, no method of pain management is considered superior or universally accepted. Acute pain following CXL is a recognised and clinically significant side effect, but few CXL studies have systematically investigated postoperative pain and its management. This review aims to improve patient pain outcomes following this increasingly common procedure.

Keywords: cornea; ocular surface; treatment other; wound healing.

Conflict of interest statement

Competing interests: None declared.

© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Figures

Figure 1
Figure 1
Impact of different CXL techniques to the corneal epithelium (black line) and sub-basal nerve plexus (wavy green line). Red dots show the CXL-induced photochemical reaction and toxic effect with the release of free radicals leading to oxidative stress and nerve damage. (A) epi-on; (B) epi-on accelerated; (C) epi-off; (D) epi-off accelerated. Illustration by Emilie S. van der Valk Bouman. CXL, corneal collagen cross-linking.

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