Tear Neuromediator and Corneal Denervation Following SMILE

Abstract

PURPOSE: To investigate the changes in tear neuromediators and corneal subbasal nerve plexus following small incision lenticule extraction (SMILE) and to study its association with different refractive power of corrections. METHODS: Thirty patients were included for tear neuromediator analysis (40 eyes) and corneal nerve analysis using in vivo confocal microscopy scans (20 eyes). Tear samples were collected preoperatively and 1 week and 1, 3, 6, and 12 months postoperatively and analyzed for the substance P, calcitonin gene-related peptide (CGRP), and nerve growth factor (NGF) concentrations using the enzyme-linked immunosor-bent assay (ELISA). RESULTS: Corneal nerve fiber density (CNFD), corneal nerve fiber length (CNFL), and corneal nerve branch density (CNBD) decreased significantly postoperatively, then gradually increased from 3 months onward, but did not recover to the baseline levels at 12 months. Tear substance P and CGRP levels remained stable over 12 months. Tear NGF levels demonstrated a small peak at 1 week before decreasing significantly compared to preoperative levels at 6 months ( P = .03) and 12 months ( P = .007). The 1-month reduction in CNFL, tear substance P, and CGRP concentrations were significantly correlated with the corrected spherical equivalent (SE) ( r = 0.71 for CNFL; r = −0.33 to −0.52 at different time points for substance P and CGRP, respectively, all P < .05). Compared to the low to moderate myopia group, the high myopia group (corrected SE greater than −6.00 diopters) had a significantly greater decrease in CNFD, significantly higher tear substance P concentrations at 1 week, 1 month, and 6 months, and significantly higher tear CGRP concentrations at 1 and 6 months. CONCLUSIONS: These results provide new insight into the neurobiological responses and their potential implications in corneal nerve damage and recovery after SMILE. High myopia treatment was associated with greater corneal denervation and neuroinflammation. [ J Refract Surg . 2021;37(8):516–523.]

Changes of Subjective Symptoms and Tear Film Biomarkers following Femto-LASIK

“…Interestingly, the increase in NGF levels in both aforementioned studies was accompanied by lower BUT and Schirmer values, which we also did not observe. Another study, however, using small incision lenticule extraction for the treatment of myopia, also found no changes in tear film NGF levels neither at one week nor at three months after surgical treatment [ 36 ].…”

“…A single-visit cross-sectional study investigating patients 12 months after Femto-LASIK and healthy participants detected an upregulated CGRP level in the Femto-LASIK cohort [ 38 ]. Moreover, in patients with myopia and treated with SMILE, the CGRP level remained stable after surgery [ 36 ]. Interestingly, in tear samples of patients with severe dry eye disease (Sjögren’s syndrome) a decreased CGRP level could be revealed via ELISA measurements.…”

Impact of Age on the Characteristics of Corneal Nerves and Corneal Epithelial Cells in Healthy Adults

“…The nerve images were analyzed as described previously. 28 In brief, an experienced masked observer selected 5 best-focused and most representative images of the subbasal nerves from 5 areas: central, superior, inferior, nasal, and temporal quadrants at different depths from both eyes, with a total of 25 images for each eye. All images were evaluated using automatic image analysis software ACCMetrics (University of Manchester, Manchester, UK).…”

Oral Peroxisome Proliferator–Activated Receptor-α Agonist Enhances Corneal Nerve Regeneration in Patients With Type 2 Diabetes

“…Tear samples were then homogenized by sonication for 20 s, followed by overnight incubation at 4°C with gentle shaking at 450 rpm. The homogenization step was repeated once before centrifugation at 11,000 rpm at 4°C for 20 min ( 24 ). The tear proteins containing clear supernatants were collected and stored at −80°C until ELISA analysis.…”