Randomized controlled trial on corneal denervation, neuroinflammation and ocular surface in corneal lenticule extraction for advanced refractive correction (CLEAR) and small incision lenticule extraction (SMILE)

TL;DR

This study compares CLEAR and SMILE eye surgeries, finding similar effects on corneal nerves and eye surface health over one year.

Contribution

The study provides a direct comparison of corneal denervation and neuroinflammation between CLEAR and SMILE surgeries.

Findings

CLEAR and SMILE caused similar, long-lasting reductions in corneal nerve fiber density and other nerve metrics.

Ocular surface assessments showed no significant differences between the two procedures over one year.

Nerve growth factor was higher after SMILE at one month, but other neuromediator levels were comparable.

Abstract

To investigate and compare the corneal denervation, tear neuromediators, and ocular surface changes following corneal lenticule extraction for advanced refractive correction (CLEAR) versus small incision lenticule extraction (SMILE).

In this randomized clinical trial, 19 patients were randomized to undergo CLEAR in one eye and SMILE in the other eye. Ocular surface assessments, in vivo confocal microscopy for seven corneal nerve parameters, four corneal dendritic cell parameters, three corneal epithelial parameters, and tear neuromediator analysis were performed preoperatively and 1, 3, 6 and 12 months postoperatively.

There were no significant differences in all ocular surface assessments between CLEAR and SMILE throughout postoperative 1 year. CLEAR and SMILE led to significant and comparable reductions of corneal nerve fiber density (CNFD), nerve branch density, total branch density, nerve fiber length, area, and fiber fractal dimension, which did not restore even at 1 year. The reduction in CNFD was significantly correlated with the corrected spherical equivalent in both surgical types. Although post-SMILE eyes had significantly higher nerve growth factor concentrations at 1 month, there was no significant difference in substance P and calcitonin gene-related peptide (CGRP) concentrations between SMILE and CLEAR.

CLEAR and SMILE had comparable effects on ocular surface, corneal denervation and postoperative neuroinflammation. Corneal nerve metrics did not restore even at 1 year for both procedures.

Trial registration number: ClinicalTrials.gov NCT06774651, registration on 14 January 2025, https://clinicaltrials.gov/study/NCT06774651.

The online version contains supplementary material available at 10.1186/s40662-025-00429-1.

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