Corneal regeneration after laser in-situ keratomileusis: wound healing process and visual outcomes

Laser in-situ keratomileusis (LASIK) is a widely performed refractive surgical procedure that provides excellent visual outcomes. Creation of the flap and stromal ablation disrupt corneal integrity and alter its function. Damaged epithelial cells release cytokines and growth factors that interact with stromal keratocytes to trigger the regeneration process. However, these interactions under the flap are limited, and stromal repair does not conclude. Keratocyte deficits and denervation are long-lasting following photoablation. Complications derived from biological variability in the wound healing response affect the predictability of LASIK surgery. Most of these complications can be prevented or effectively treated with minor impact on optical quality and few visual consequences. J Emmetropia 2015; 4: 223-238 Submitted 10/24/2014 Revised 1/7/2015 Accepted 10/26/2015 1Department of Neuroscience, University of the Basque Country UPV/EHU, Leioa, Bilbao. 2 Department of Visual Science, VallmedicVision, The International Eye Clinic, Escaldes-Engordany, Andorra. Financial disclosure: The authors have no commercial or proprietary interest in the products mentioned herein. Corresponding Author: Javier Tomás-Juan VallmedicVision-The International Eye Clinic Avinguda Nacions Unides 17. AD700 Escaldes-Engordany, Andorra. E-mail: [email protected] UPDATE/REVIEW Photorefractive keratectomy (PRK) was the first refractive surgery to use excimer laser to correct refractive errors. In PRK, corneal epithelium is removed and excimer laser acts on the anterior stroma to remodel the corneal curvature and induce refractive changes1-6. PRK is the refractive surgery of choice in certain situations, e.g. in the treatment of residual refractive errors after laser in-situ keratomileusis (LASIK)7, in thin corneas, irregular topographies as is the case of post-RK or post-keratoplasty8, high ocular aberrations9,10, in basement membrane dystrophy and in professions with high risk of flap dislocation. PRK gradually lost popularity because of postoperative pain, corneal haze, and slow corneal and visual recovery2,5,6. LASIK, in contrast, uses a modified procedure that preserves the corneal epithelium, thus allowing faster visual recovery and reducing postoperative discomfort. It has therefore become the elective procedure in refractive surgery11. In this technique, a lamellar hinged corneal flap is created and the exposed stromal bed is ablated. Although a microkeratome was originally used to create the flap, this has been superseded by femtosecond laser12, as it presents fewer flap-associated complications, such as incomplete or irregular flaps, buttonholes, epithelial defects, or dry eye, and allows flap thickness to be precisely adjusted. Femto-LASIK has a faster recovery time, owing to thinner and more uniform flap geometry. New advances in technology are improving the safety of LASIK and refining the results. Nevertheless, biological variability in the wound-healing response and the tendency of the cornea to smooth out irregularities through stromal remodeling and epithelial hyperplasia13 have a major impact on the end results and predictability of LASIK. The corneal regeneration process follows a series of well-defined steps14,15 that can be broadly classified into two stages: active wound healing and tissue remodeling. Any disturbance in the balance of molecules that regulate corneal regeneration after LASIK has the potential to produce undesirable complications. Another approach that combines PRK and LASIK concepts is laser-assisted subepithelial keratomileusis (LASEK), also known as Epi-LASIK or Epithelial-LASIK. This procedure was developed to avoid the complications derived from flap creation16, although these had already been minimized with the introduction of femtosecond17,18.