Cytokines and Chemokines profile after Corneal-Crosslinking with Riboflavin at 4°C

Abstract

Purpose : Postoperative pain is a major disadvantage after crosslinking (CXL). It may be due to the locally released inflammatory mediators caused by corneal debridement. We performed a prospective and interventional randomized clinical trial to explore if corneal cooling has a role in decreasing the release of inflammatory cytokines in accelerated CXL in patients with keratoconus.

Methods : We conducted the research at Institute of Ophthalmology “Conde de Valenciana”. A total of 34 patients were randomly assigned to one of the following groups: 17 to the cold riboflavin (4°C) group and 17 to the control group (riboflavin at room temperature). The inclusion criteria were patients older than 18 years of age with keratoconus who needed treatment with CXL because the evidence of progression. The exclusion criteria were patients who had CXL without epithelial debridement and any other ocular or systemic pathologies. A tear sample was taken to all the participants before the procedure and 2, 24, 48 and 72 hours post-op. The main outcome measure was the determination of cytokines and chemokines using the Proteome Profiler Human Cytokine Array Kit in the tear of both groups. The data analysis was done by the determination of the average signal (pixel density) of the pair of duplicate spots representing each cytokine using a transmission-mode scanner and image analysis software.

Results : Overall there was an upregulation of cytokines and chemokines in both groups, especially at 2 hours post-op, the control group had a more evident increase than the cold riboflavin group. The most relevant findings were that the Interleukin-1 receptor antagonist (IL-1ra) increased slightly at 2 hours post-op and decreased at 24 and 72 hours post-op in the control group, whereas in the cold riboflavin group increased significantly at 2 hours post-op and decreased at 24 and 72 hours post-op. IL-6 increased significantly at 2 and 24 hours post-op in the control group, whereas in the cold riboflavin group it only had a slight increment at 24 hours post-op. IL-18 increased at 2 and 72 hours post-op in both groups (with significant higher concentrations at 2 hours post-op in the control group) and decreased at 24 hours post-op in both groups (despairing in the cold riboflavin group).

Conclusions : Our results suggest that using cold riboflavin may decrease the inflammatory response and therefore decrease corneal pain after crosslinking.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.