Comparative Analysis of Corneal Wound Healing: Differential Molecular Responses in Tears Following PRK, FS-LASIK, and SMILE Procedures

Background/Objectives: In this study, we aimed to analyze the changes in the expression profiles of selected messenger RNAs (mRNAs) and their encoded proteins in the tears of patients undergoing photorefractive keratectomy (PRK), femtosecond-assisted laser in situ keratomileusis (FS-LASIK), and small-incision lenticule extraction (SMILE) procedures. Methods: A total of 120 patients were divided into three groups based on the laser vision correction (LVC) procedure: PRK, FS-LASIK, or SMILE. Tear samples were collected preoperatively and at 1, 7, 30, and 180 days postoperatively. The expression levels of selected messenger RNAs (mRNAs) and proteins were analyzed by using reverse transcription quantitative polymerase chain reaction (RT-qPCR) and enzyme-linked immunosorbent assay (ELISA), respectively. Results: PRK and FS-LASIK elicited significantly stronger biological responses than SMILE. Interleukin-15 (<i>IL-15</i>) expression increased notably in the PRK and FS-LASIK groups, with mRNA levels reaching fold changes of 4.65 ± 0.65 and 4.99 ± 0.28, respectively, on day 1, compared with only 2.09 ± 0.23 in the SMILE group. Vascular endothelial growth factor A (<i>VEGFA</i>) levels were also elevated in the PRK (2.98 ± 0.23 fold change) and FS-LASIK groups (3.45 ± 1.09 fold change) on day 1, while the SMILE group showed minimal fluctuations. The protein concentration analysis based on the ELISA confirmed these trends, with IL-15 levels peaking at 54.2 ± 2.5 pg/mL in the PRK group and 52.8 ± 3.1 pg/mL in the FS-LASIK group, compared with 32.4 ± 1.9 pg/mL in the SMILE group on day 1. Similarly, VEGFA protein concentrations were the highest in the PRK (72.4 ± 4.1 pg/mL) and FS-LASIK patients (69.5 ± 3.8 pg/mL) on day 1 but remained low in the SMILE patients (45.6 ± 2.3 pg/mL). By day 180, gene expression and protein levels in all groups had stabilized, returning to near-preoperative values. Conclusions: PRK and FS-LASIK induced more pronounced molecular and protein-level changes during corneal wound healing than the less invasive SMILE procedure, indicating stronger biological responses. These findings suggest that tailored postoperative care based on the specific procedure could optimize healing and patient outcomes. However, further research with larger sample sizes and longer follow-ups is needed to confirm these observations and develop personalized treatment strategies.