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Anterior Segment Cornea
Corneal Wound Healing After Keratorefractive Procedures
Irene C Kuo
Associate Professor of Ophthalmology, Cornea and Refractive Surgery Services, Wilmer Eye Institute, Johns Hopkins University School of Medicine
Abstract
Research into corneal wound healing is gaining renewed interest with the increasing volume of keratorefractive procedures. Such research
may help avoid the complication of ectasia after laser refractive surgery. There are three histopathological types of wound healing after
keratorefractive surgery – whether laser refractive surgery, penetrating keratoplasty or radial keratotomy – and these are reviewed in this
paper. They are hypercellular fibrotic stromal scar preceded by activated keratocytes, epithelial hyperplasia or hypertrophy and
hypocellular primitive stromal scar. All can be identified with light, electron and immunofluorescence microscopy (or, with less detail, by
confocal microscopy). A single procedure can manifest all three types of wound healing. Tissue destruction is part of tissue remodelling,
but in successful procedures destruction cannot be uncontrolled or excessive. The elucidation of the signalling components remains an
important area of research.
Keywords
Wound healing, laser-assisted in situ keratomileusis (LASIK), keratorefractive, refractive surgery, keratocyte
Disclosure: The author has no conflicts of interest to declare.
Received: 6 November 2009 Accepted: 14 December 2009
Correspondence: Irene C Kuo, Wilmer Eye Institute, 4924 Campbell Blvd #100, Baltimore, MD 21236, US. E:
ickuo@jhmi.edu
This review of corneal wound healing following refractive surgery is There have been reports of some anteroposterior lamellar branching
modified and updated from a previous review of general corneal in the mid-stroma and of frequent interfibrillar bridging filament
wound healing.
1
networks composed of type VI collagen filaments present throughout
the entire corneal stroma. Between the most posterior layer of the
To help understand the wound healing response after keratorefractive stroma and Descemet’s membrane is a thin 0.5µm layer of loosely
procedures, it is first important to review the structure of the cornea. arranged collagen fibrils and fibronectin. One explanation for the
Understanding the structure also can help explain some of the higher risk of ectasia after laser-assisted in situ keratomileusis (LASIK)
complications that can arise as a result of refractive surgery. compared with photorefractive keratectomy (PRK) therapy is that in
LASIK the strongest portion of the cornea – the anterior stroma –
Bowman’s layer is composed of 22nm heterotypical type I collagen in the thinner central (as opposed to thicker peripheral) cornea is
fibrils, which are randomly orientated (mean direction 45º to the transected for creation of the flap.
corneal surface).
2
Immediately beneath Bowman’s membrane, the
cornea is arranged such that there are about 300 lamellae centrally Basically, there are three histopathological types of wound healing
and 500 lamellae peripherally. Each is composed of uniformly parallel- after keratorefractive surgery,
5
whether excimer laser ablation,
directed, 25nm heterotypical type I collagen fibrils with flattened penetrating keratoplasty
6,7
or radial keratotomy:
8–12
keratocytes present between some adjacent lamellae. In the anterior
third of the stroma, lamellae are orientated in oblique directions to hypercellular fibrotic stromal scar preceded by activated
the corneal surface; they branch extensively and are interwoven with keratocytes;
other lamellar layers both anteroposteriorly and horizontally. epithelial hyperplasia or hypertrophy; and
hypocellular primitive stromal scar.
The structure of the lamellae in the anterior third of the stroma
most resembles the pericardium, which prevents overdilation of the All of these can be identified with light, electron and immuno-
heart and formation of aneurysms.
3
However, the lamellar structure fluorescence microscopy (or, with less detail, by confocal microscopy).
12
of the posterior two-thirds of the stroma most resembles that of
the annulus fibrosis of the intervertebral disc, functioning to In animals, it has been demonstrated by in vivo confocal microscopy
dampen the compressive forces placed on the disc without rigidly and immunohistology that there are three morphologically and
maintaining shape.
4
The lamellae in the posterior stroma are functionally distinct types of keratocyte. These arise from the normal,
orientated parallel to the corneal surface and are thicker and wider quiescent, undamaged keratocyte population after corneal stromal
than anterior lamellae. injury, whether mechanical, chemical or by excimer laser:
64 © TOUCH BRIEFINGS 2009
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