Corneal re-innervation following refractive surgery treatments

Abstract

Laser refractive surgery is one of the most performed surgical procedures in the world. Although regarded safe and efficient, it has side effects. All of the laser based refractive surgical procedures invoke corneal nerve injury to some degree. The impact of this denervation can range from mild discomfort to neurotrophic corneas. Currently, three techniques are widely used for laser vision correction: small incision lenticule extraction, laser-assisted keratomileusis in situ and photorefractive keratotomy. Each of these techniques affects corneal innervation differently and has a different pattern of nerve regeneration. The purpose of this review is to summarize the different underlying mechanisms for corneal nerve injury and compare the different patterns of corneal reinnervation.

Keywords: corneal nerve; corneal sensation; in vivo confocal microscopy; laser-assisted keratomileusis in situ; photorefractive keratotomy; refractive surgery; small incision manual lenticule extraction.

Figure 1

Histological crossection of a human cornea (hematoxylin-eosin staining). Montage of a whole cornea and an insert of the corneal layers (4× magnification). The red arrowheads correspond to the epithelial layer; the corneal stroma is comprised between the white brackets; and the green arrowheads delineate the endothelial layer. The Bowman layer is delimited by the blue dashed and yellow dotted lines. The image is provided by Singapore Eye Research Institute Image Library.

Figure 2

Corneal nerve distribution. Confocal microscopy montage of a whole cornea mount stained with DAPI (blue); phalloidin (red) and TuJ-1 (green). The nerve distribution is shown in two different perspectives. (A) Crossection of the whole cornea 5× magnification, the white square shows a 20× magnification, the white arrowheads show intense green signal – which are the stromal and sub-basal nerves running parallel to collagen fibers. (B) Flat-mount confocal 3D image of a SMILE lenticule; images from the top to bottom of the lenticule were taken 5 µm apart and stacked into a single frame; the white arrows indicate the disposition of corneal nerves. SMILE: Small incision manual lenticule extraction; DAPI: 4’,6-diamidino-2-phenylindole. The image is provided by Singapore Eye Research Institute Image Library.

Figure 3

Schematics of the different refractive surgical procedures. (A) Small incision lenticule extraction; (B) laser-assisted keratomileusis in situ; (C) photorrefractive keratectomy.

Figure 4

Corneal re-innervation. The chart displays the mean recovery of corneal nerve density over time compared to baseline. The colored lines represent the different procedures: blue for PRK; red for LASIK; and green for SMILE. The error bars represent the standard deviation. PRK: Photorefractive keratotomy; LASIK: laser-assisted keratomileusis in situ; SMILE: small incision manual lenticule extraction.

Figure 5

Corneal sensitivity recovery. The chart displays the mean recovery of corneal sensitivity over time compared to baseline. The colored lines represent the different procedures: blue for PRK; red for LASIK; and green for SMILE. The error bars represent the standard deviation. PRK: Photorefractive keratotomy; LASIK: laser-assisted keratomileusis in situ; SMILE: small incision manual lenticule extraction.