Patient Age Affects Recovery From SMILE Surgery

New Vision clinic, main center for refractive surgery in France, with cutting-edge technology for all eye laser operations. Eye operation using the SMILE, Small Incision Lenticule Extraction, laser technique. It is a new generation of treatment which enables short-sightedness to be corrected without removing the superficial layer of the cornea, nor opening it. The SMILE technique involves producing with the Femtosecond laser, a lenticule, thin slice, in 3D in the thickness of the cornea, and removing it with a micro incision in the shape of a smile. The worse the short-sightedness, the thicker the lenticule. (Photo by: BSIP/Universal Images Group via Getty Images)
Research shows a significant difference in recovery speed in patients of variou ages.

After small incision lenticule extraction (SMILE) surgery, the central nerve fiber length of the cornea recovered faster in patients under age 30, according to researchers. They also found that corneal nerve recovery becomes slower with age starting 1 year after undergoing the procedure. 

Like other types of refractive surgeries, SMILE damages the corneal nerve, which can result in postoperative dry eye and neurotrophic epitheliopathy, according to investigators. However, how corneas heal after SMILE is a complex process that is not well understood. Investigators believe that healing is impacted by several factors, including age.

To investigate the effect of age on wound healing after SMILE, researchers conducted a prospective study. In total, 216 patients were divided into 4 age groups: ages 18 to 20 (n=38, Group I), ages 21 to 30 (n=84, Group Ⅱ), ages 31 to 40 (n=58, Group Ⅲ), and ages 41 to 50 (n=36, Group IV). The density of corneal epithelial wing cells, basal cells, corneal stromal cells, endothelial cells, and corneal nerves were examined before surgery and 1 month, 3 months, 6 months and 1 year after SMILE. The team analyzed the central nerve fiber length (CNFL), the central corneal nerve fiber density (CNFD), and the central corneal nerve branch density (CNBD). Corneal stroma lenticules were obtained from SMILE to analyze metabolites.

Investigators found no significant difference in the central corneal epithelial wing cells, stromal cells, and endothelial cells among the four groups. Specifically, the CNFL was 21.90±1.68 mm/mm2 in Group Ⅰ and 21.63±2.09 mm/mm2 in Group Ⅱ 1 year postoperatively, representing a return to the preoperative level. However, the CNFL of Group Ⅲ (19.40±0.98 mm/mm2) and Group Ⅳ (18.94±0.72 mm/mm2) was lower preoperatively (P <.01). In addition, CNFL repair had a negative correlation with age after surgery (P <.01), as did the CNFD and the CNBD (P <.05).

Researchers screened the “significantly different” metabolites between the 18-30 age group (including Group I and Group Ⅱ) and the other 2 groups, finding 6 common remarkably different metabolites. Meanwhile, 5 unique metabolites were identified only between the 18-30 and the 31-40 age groups. Six unique metabolites were identified only between the 18-30 and the 41-50 age groups. These metabolites were mainly related to inflammation, oxidation, nerve protection, and regeneration.

Researchers noted several limitations of their work, including that the 41-50 age group included fewer patients than the other groups and that only the central section of the cornea was used to evaluate nerve fiber density. 


Li M, Liu L, Shi Y, et al. Age-related differences in corneal nerve regeneration after SMILE and the mechanism revealed by metabolomics. Exp Eye Res. 2021;209(8):108665., doi:10.1016/j.exer.2021.108665