Neuropathic corneal pain following refractive surgery : risk factors, clinical manifestations, imaging and proteomic characteristics

Abstract

Background/aims: To identify the risk factors for neuropathic corneal pain (NCP) following corneal refractive surgery and to report its clinical manifestations, imaging and proteomic characteristics. Methods: This 1 year prospective cohort study included 100 eyes that underwent small incision lenticule extraction (SMILE) or laser-assisted in situ keratomileusis (LASIK). Ocular surface assessments, in-vivo confocal microscopy scans, tear neuromediators and proteomics analyses were performed. NCP was assessed using the ocular pain assessment survey. Univariate and multivariate analyses were conducted to identify the risk factors associated with postoperative NCP. Results: The incidence of NCP was 13.3% and 10.5% after SMILE and LASIK, respectively (p=0.70). In SMILE, preoperative manifest refractive spherical equivalent (MRSE) and spherical power (both p=0.02) were significantly higher in the NCP compared with the non-NCP group. In LASIK, NCP eyes had a significantly lower corneal nerve fibre length (CNFL) (p=0.02), lower nerve fractal dimension (p=0.003), higher nerve fibre width (p=0.04) and larger neuroma area (p=0.04) than non-NCP eyes. In SMILE, higher preoperative MRSE was a significant risk factor for postoperative NCP (95% CI: 0.48—1.96, p=0.04). An MRSE greater than −8.0 diopter was 9.57 times more likely to develop postoperative NCP (OR=9.57, p=0.002). In LASIK, lower preoperative corneal nerve fibre density (95% CI:0.13—1.11, p=0.05) and CNFL (95% CI:0.09—1.25, p=0.05) were significant risk factors for postoperative NCP. Significant increases in tear nerve growth factor, calcitonin gene-related peptide, Frizzled class receptor 7 and nucleoside-diphosphate kinase three were observed in postoperative NCP. Conclusions: The reported characteristics and risk factors would identify patients susceptible to NCP after corneal refractive surgery.