Impact of corneal sub-basal nerve plexus on epithelial thickness after small incision lenticule extraction (SMILE): a quantitative assessment using in vivo confocal microscopy and optical coherence tomography

Background: Quantitative assessment of corneal epithelial thickness (CET) has attracted a great attention for its wide application in refractive surgeries. The corneal nerves are crucial for epithelial homeostasis, and nerve injury due to corneal refractive surgery may affect the epithelia; however, few clinical studies have investigated this relationship. Our study aimed to observe changes in epithelial thickness and sub-basal nerve plexus (SNP) profile after small incision lenticule extraction (SMILE) for low-to-moderate myopia [spherical refraction of -6.0 to 0 diopters (D)], and investigate the relationship between them. Methods: This prospective observational study included 52 eyes treated with SMILE from March to May 2023 at Tianjin Medical University Eye Hospital. The epithelial thickness was measured across the central and concentric (paracentral, mid-peripheral, and peripheral) regions using spectral-domain optical coherence tomography (SD-OCT). SNPs were observed in the central and peripheral (temporal, superior, nasal, and inferior) areas using in vivo confocal microscopy (IVCM), and seven nerve parameters were assessed. All eyes were examined preoperatively and 1 week, 1 month, and 6 months postoperatively. Pearson's correlation was employed to investigate the association between anterior Q-value (corneal asphericity) and epithelial thickness. Partial correlation was adopted to examine the relationship between epithelial thickness and corresponding nerve parameters. Results: Both epithelial thickness and SNP exhibited changes after SMILE. Six months postoperatively, epithelial thickness in the central and paracentral regions increased (all P<0.05), with thickening particularly pronounced in the inferotemporal, temporal, and inferior sections of the paracentral region, and the anterior Q-value was positively correlated with epithelial thickness in the inferonasal, inferior, and inferotemporal sections (inferonasal section: r=0.293, P=0.035; inferior section: r=0.396, P=0.004; inferotemporal section: r=0.374, P=0.006). Furthermore, most central, superior, and nasal nerve parameters had still not reached preoperative levels, while most temporal and inferior nerve parameters had reached or exceeded preoperative levels, and epithelial thickness was positively correlated with corresponding nerve parameters [corneal nerve fiber density (CNFD): r=0.171, P=0.006; corneal nerve branch density (CNBD): r=0.137, P=0.028; corneal nerve fiber length (CNFL): r=0.172, P=0.006; corneal nerve fiber total branch density (CNTB): r=0.141, P=0.024; corneal nerve fiber area (CNFA): r=0.164, P=0.008]. Conclusions: Uneven epithelial thickness changes were observed after SMILE, regional epithelial thickening increased corneal oblateness. Non-uniform SNP regeneration was also observed, positive correlation between epithelial thickness and nerve parameters indicated the impact of nerves on epithelia, which may enhance the clinical value of epithelial thickness measurement.