PURPOSE: To compare long-term corneal nerve status following small incision lenticule extraction (SMILE) versus laser in situ keratomileusis (LASIK). METHODS: Twenty-four patients were randomized to receive SMILE in one eye and LASIK in the other eye. In vivo confocal microscopy examination and dry eye assessments were performed at a mean of 4.1 years postoperatively. The patients were further divided into two groups based on the mean assessment time: 2.7 years postoperatively (2.7 years group) and 5.5 years postoperatively (5.5 years group). Another 6 age-matched normal patients were recruited. RESULTS: At 4.1 years, LASIK eyes had significantly less corneal nerve fiber density (CNFD), corneal nerve branch density (CNBD), corneal nerve fiber length (CNFL), and corneal total branch density and significantly more nerves with beading than SMILE eyes. The CNFD, CNBD, CNFL, and number of nerves with sprouting were significantly higher in the 5.5 years group than in the 2.7 years group, in both types of surgery, suggesting persistent nerve regeneration. The CNBD and CNFD in the 5.5 years group, regardless of surgical types, were significantly lower than those in the control group, indicating the nerve status had not recovered to normal ranges even at 5.5 years. High myopic treatment resulted in significantly reduced CNFD with LASIK but not with SMILE. There were no significant differences in the dry eye parameters between the two procedures at 4.1 years postoperatively. CONCLUSIONS: The impact on corneal nerves following refractive surgery is long-lasting. SMILE had better nerve preservation and regeneration than LASIK, but neither procedure had recovered nerve status to normal levels even at 5.5 years. [ J Refract Surg . 2020;36(10):653–660.]
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