Safety and efficacy of small incision lenticule extraction combined with prophylactic corneal cross-linking (SMILE-Xtra) for myopia: a systematic review and meta-analysis

Introduction: Myopia is a common refractive error worldwide, and small incision lenticule extraction (SMILE) has become an established surgical option because of its favorable visual outcomes and better preservation of corneal biomechanics. Prophylactic corneal collagen cross-linking combined with SMILE (SMILE-Xtra) has been introduced to enhance corneal stability in patients at increased risk of postoperative ectasia. However, the available evidence regarding its safety and efficacy remains inconclusive.

Objective: To evaluate the safety and efficacy of SMILE-Xtra compared with conventional SMILE in patients with myopia, focusing on refractive outcomes, corneal stability, and postoperative complications.

Methods: A systematic review and meta-analysis was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines. PubMed/MEDLINE, Scopus, and Web of Science (WOS) were systematically searched from inception to May 2026. Comparative studies evaluating SMILE-Xtra versus conventional SMILE in patients with myopia or myopic astigmatism were included. Pooled mean differences (MDs) with 95% confidence intervals (CIs) were calculated using a random-effects model.

Results: Seven studies were included in the review. No significant differences were found between SMILE-Xtra and conventional SMILE regarding spherical equivalent refraction, central corneal thickness, or mean keratometry. However, SMILE-Xtra demonstrated a significantly lower postoperative refractive cylinder. Overall, the included studies reported favorable safety outcomes with no evidence of increased major complications following SMILE-Xtra.

Conclusion: SMILE-Xtra appears to be a safe and effective adjunct to conventional SMILE, particularly for patients at higher risk of postoperative corneal ectasia, while maintaining comparable refractive outcomes. Further prospective randomized studies with standardized protocols and longer follow-up are required to confirm its long-term safety and efficacy.

Keywords: Myopia, SMILE, SMILE-Xtra, Corneal Collagen Cross-Linking, Systematic Review, Meta-Analysis.

Abdalrhman Alblwan is a General Practitioner and recent MBBS graduate (First-Class Honors, GPA 4.74/5.00, ranked 2nd in class) from the College of Medicine, Jouf University, Saudi Arabia. He has completed clinical attachments in ophthalmology at King Khaled Eye Specialist Hospital and the Ministry of National Guard Health Affairs, Riyadh. His research interests include corneal disease, glaucoma, and diabetic retinopathy, and he is the innovator behind CorneaX, a diagnostic lens for keratoconus. He is a member of the World Society of Paediatric Ophthalmology and Strabismus (WSPOS) and the Ophthalmology Interest Group at Al-Jouf University.