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

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.

Intracanalicular dexamethasone insert for post–corneal crosslinking inflammation and pain: the LINK study

“…[3][4][5][6][7] Removal of the epithelium can induce afferent nerve injury and inflammation, leading to acute pain over a few days that typically declines as the cornea re-epithelializes. [9][10][11][12][13]22 Despite patient reassurance, most need some form of topical or oral pain medications to manage post-CXL pain and inflammation, at least in the short-term. [9][10][11][12][13]22 There is a multipronged strategy to preventing and managing CXL-related pain and discomfort; this involves judicious application of anesthetic drops before and during CXL, postoperative topical steroids and cycloplegics, placement of a bandage contact lens, and utilization of oral pain medications (eg, NSAIDs and narcotics) as necessary.…”

“…[17][18][19][20]25 The tear film is an integral component in corneal epithelial healing; the fewer disturbances it experiences portend potentially easier re-epithelialization for post-CXL eyes. 9,[13][14][15][16][17][18][19][25][26][27][28][29] It is also worthwhile to note that all CXL patients in this study had a bandage contact lens placed at the time of CXL completion. As the ocular surface is a dynamic environment, and factors such as reflex tearing, blinking, tear film quality, and surface characteristics all play a role in topically administered medications, it may be hypothesized that in terms of re-epithelialization and maintenance of the ocular surface milieu, the topical prednisolone may not have completely penetrated to the ocular surface after CXL because of the application of a BCL, whereas the dexamethasone insert was not necessarily impeded in this manner.…”

“…[3][4][5][6][7][8] Although CXL has now become the standard of care, the immediate postoperative period can be quite painful despite the use of anti-inflammatory medications/eyedrops. 5,[9][10][11][12][13][14][15] There is no standard-of-care medication regimen for the management of pain and/or inflammation after CXL, although most cornea specialists agree on the use of an antibiotic and steroid eyedrop in the immediate postprocedural period. However, the steroid tapering schedule and the use of additional medications (eg, topical nonsteroidal anti-inflammatory [NSAID] eyedrops and oral medications) vary among practitioners.…”

A New Postoperative Regimen after CXL and PRK Using Topical NSAID and Steroids on the Open Ocular Surface

“…This frequent instillation may result in unreasonably high doses being applied to the eye. For these reasons, topical NSAID therapy has not formed part of most post-PRK, TransPRK, or CXL pain management regimens [ 9 ].…”

Topical analgesics for acute corneal pain: current options and emerging therapeutics

“…11,12 To our knowledge, no cases of chronic pain after CXL have been reported in the literature. 13 Despite the range of available topical ocular and systemic analgesics, no one strategy is sufficient to control acute corneal pain across all clinical settings (Figure 2). In addition to addressing the limitations of these drugs, several repurposed and new topical ocular therapies will be discussed, including autologous tear serums, opioid system modulators, and endocannabinoid system (ECS) modulators.…”