Predicting pain after corneal refractive surgery: Analysis of the pre-surgical tear proteome

Abstract

Purpose : A subset of refractive surgery patients will have eye pain beyond the immediate recovery period. There is currently no reliable way to determine patients at risk for this persistent postoperative pain. This prospective, observational clinical study sought to identify presurgical tear protein expression patterns in patients reporting pain 3 months after LASIK or PRK.

Methods : Participants (n = 48) were patients having corneal refractive surgery at two clinical sites: Portland, OR and Miami, FL. Participants rated their eye pain on an 11-point numeric rating scale ((NRS); 0 = no pain; 10 = worst pain) and provided tear fluid samples on Schirmer strips at baseline (prior to surgery) and 3 months after surgery. Tears from baseline were analyzed by tandem mass tag (TMT) spectrometry. Protein-wise fold-changes and statistical modeling were used to investigate differences in protein expression patterns in patients with persistent pain. Functional protein associations were investigated with the STRING database (Swiss Institute of Bioinformatics).

Results : 16 participants reporting pain (“Pain,” NRS ≥ 3) and 32 participants reporting no pain (“No Pain,” NRS ≤ 1) at 3 months after surgery were included. Participants (mean age=34.8 years±8.54 SD) were predominantly female (64.6%), wore contact lenses (CL) prior to surgery (77.1%), most had LASIK (83.3%), and 50% were from each site. There was no difference between Pain and No Pain groups in recruitment site, age, sex, procedure (PRK or LASIK), CL wear prior to surgery, or Schirmer length. From 2443 total detected proteins, 46 were either up- or down-regulated in Pain patients as determined by fold-change and statistical modeling criteria. Some of the 46 proteins have been previously linked to ocular surface function, including epidermal growth factor (EGF) and its receptor (EGFR), prostate stem cell antigen A (PSCA), and involucrin (IVL). STRING analysis revealed a significant number of interactions within the list of proteins with differential expression in Pain.

Conclusions : Proteomic analyses and statistical modeling identified differences in the pre-surgical tear proteome of participants later reporting eye pain 3 months after LASIK or PRK compared to their counterparts who reported no pain. These data highlight the promise of tear proteins as potential biomarkers for assessing persistent post-refractive surgery pain risk.

This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.