Reversible Femtosecond Laser-Assisted Myopia Correction: A Non-Human Primate Study of Lenticule Re-Implantation after Refractive Lenticule Extraction

Abstract

LASIK (laser-assisted in situ keratomileusis) is a common laser refractive procedure for myopia and astigmatism, involving permanent removal of anterior corneal stromal tissue by excimer ablation beneath a hinged flap. Correction of refractive error is achieved by the resulting change in the curvature of the cornea and is limited by central corneal thickness, as a thin residual stromal bed may result in biomechanical instability of the cornea. A recently developed alternative to LASIK called Refractive Lenticule Extraction (ReLEx) utilizes solely a femtosecond laser (FSL) to incise an intrastromal refractive lenticule (RL), which results in reshaping the corneal curvature and correcting the myopia and/or astigmatism. As the RL is extracted intact in the ReLEx, we hypothesized that it could be cryopreserved and re-implanted at a later date to restore corneal stromal volume, in the event of keratectasia, making ReLEx a potentially reversible procedure, unlike LASIK. In this study, we re-implanted cryopreserved RLs in a non-human primate model of ReLEx. Mild intrastromal haze, noted during the first 2 weeks after re-implantation, subsided after 8 weeks. Refractive parameters including corneal thickness, anterior curvature and refractive error indices were restored to near pre-operative values after the re-implantation. Immunohistochemistry revealed no myofibroblast formation or abnormal collagen type I expression after 8 weeks, and a significant attenuation of fibronectin and tenascin expression from week 8 to 16 after re-implantation. In addition, keratocyte re-population could be found along the implanted RL interfaces. Our findings suggest that RL cryopreservation and re-implantation after ReLEx appears feasible, suggesting the possibility of potential reversibility of the procedure, and possible future uses of RLs in treating other corneal disorders and refractive errors.

Comparative Study of nJ- and μJ-Energy Level Femtosecond Lasers: Evaluation of Flap Adhesion Strength, Stromal Bed Quality, and Tissue Responses

“…21,29 The reflectivity appears to be reduced over time as the corneas recovered and the collagen lattice formation restored. 30 Here, we did not find any significant difference in the reflectivity of the flap interface between the VisuMax and LDV groups. We also counted the keratocytes that were present at 10 lm anterior and posterior from the flap interface to assess the collateral effect of the laser delivery to the cornea.…”

Nerve regeneration by human corneal stromal keratocytes and stromal fibroblasts

“…Our previous study showed that SMILE induced less CSK apoptosis and inflammation compared to LASIK, thus creating a much thinner acellular zone46. The CSKs remained viable and could repopulate early along the femtosecond laser incision site and this appeared to occur through the migration of adjacent keratocytes4849. SMILE has also been shown to damage less stromal nerves, preserve the sub-basal nerve plexus and have faster nerve recovery compare to LASIK1650.…”

In vivo confocal microscopic investigation of the cornea after autologous implantation of lenticules obtained through small incision lenticule extraction for treatment of hyperopia

“…Although there is no previously published literature on in vivo examinations of changes in the human stroma after autologous lenticule implantation, several studies have described it in animal corneas. Riau et al re‐implanted cryopreserved refractive lenticules obtained from refractive lenticule extraction in monkeys and found that the anterior and posterior borders of the lenticule were repopulated with keratocytes by postoperative week eight. Angunawela et al extracted refractive lenticules and stored them at −80°C for 28 days, then implanted them autologously in six New Zealand White rabbits.…”